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Background: Nonpuerperal mastitis (NPM) is a disease that presents with redness, swelling, heat, and pain during nonlactation and can often be confused with breast cancer. The etiology of NPM remains elusive; however, emerging clinical evidence suggests a potential involvement of lipid metabolism. Method: Liquid chromatography‒mass spectrometry (LC/MS)-based untargeted lipidomics analysis combined with multivariate statistics was performed to investigate the NPM lipid change in breast tissue. Twenty patients with NPM and 10 controls were enrolled in this study. Results: The results revealed significant differences in lipidomics profiles, and a total of 16 subclasses with 14,012 different lipids were identified in positive and negative ion modes. Among these lipids, triglycerides (TGs), phosphatidylethanolamines (PEs) and cardiolipins (CLs) were the top three lipid components between the NPM and control groups. Subsequently, a total of 35 lipids were subjected to screening as potential biomarkers, and the chosen lipid biomarkers exhibited enhanced discriminatory capability between the two groups. Furthermore, pathway analysis elucidated that the aforementioned alterations in lipids were primarily associated with the arachidonic acid metabolic pathway. The correlation between distinct lipid populations and clinical phenotypes was assessed through weighted gene coexpression network analysis (WGCNA). Conclusions: This study demonstrates that untargeted lipidomics assays conducted on breast tissue samples from patients with NPM exhibit noteworthy alterations in lipidomes. The findings of this study highlight the substantial involvement of arachidonic acid metabolism in lipid metabolism within the context of NPM. Consequently, this study offers valuable insights that can contribute to a more comprehensive comprehension of NPM in subsequent investigations. Trial registration: Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine (Number: 2019-702-57; Date: July 2019). [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) is a highly aggressive and lethal brain tumor with limited treatment options, such as the chemotherapeutic agent, temozolomide (TMZ). However, many GBM tumors develop resistance to TMZ, which is a major obstacle to effective therapy. Recently, dysregulated lipid metabolism has emerged as an important factor contributing to TMZ resistance in GBM. The dysregulation of lipid metabolism is a hallmark of cancer and alterations in lipid metabolism have been linked to multiple aspects of tumor biology, including proliferation, migration, and resistance to therapy. In this review, we aimed to summarize current knowledge on lipid metabolism in TMZ-resistant GBM, including key metabolites and proteins involved in lipid synthesis, uptake, and utilization, and recent advances in the application of metabolomics to study lipid metabolism in GBM. We also discussed the potential of lipid metabolism as a target for novel therapeutic interventions. Finally, we highlighted the challenges and opportunities associated with developing these interventions for clinical use, and the need for further research to fully understand the role of lipid metabolism in TMZ resistance in GBM. Our review suggests that targeting dysregulated lipid metabolism may be a promising approach to overcome TMZ resistance and improve outcomes in patients with GBM. [ABSTRACT FROM AUTHOR]

Endometrial carcinoma (EC) has become one of the most common gynecological malignant neoplasms in developed countries worldwide. Studies have shown that this may be closely related to the abnormal metabolism of blood lipids, which was the most significant metabolic change in the human body in this cancer. In this review, we focus on the correlation between lipid metabolism and EC and discuss the evidence that abnormal lipid metabolism promotes an increase in EC growth and metabolism, as well as the regulatory mechanism and related signaling pathways involved in this relationship. In addition, we also discussed the research progress of targeted therapies and drug treatments for EC that act on lipid metabolism, and statins are expected to become adjuvant drugs for EC in the future. This review will provide a systematic view for a better understanding of the etiological relationship between lipid metabolism and EC and further open up new therapeutic possibilities and effective treatments for EC by targeting lipid metabolism. [ABSTRACT FROM AUTHOR]

Background: Dihydromyricetin (DMY) is a natural flavonoid with anti-nonalcoholic steatohepatitis (NASH) activity. However, the effects of DMY on the composition of lipids and bile acids (BAs) in serum, and gut microbiota (GM) in ileum of mice with NASH are not clear. Methods: After male C57BL/6 mice was fed with methionine and choline deficiency (MCD) diet and simultaneously administered with DMY (300 mg/kg/day) by gavage for 8 weeks, the pathological changes of liver tissue were observed by Oil Red O, hematoxylin eosin and Masson staining, the levels of serum alaninea minotransferase, aspartate aminotransferase and liver triglyceride, malonic dialdehyde were detected by the detection kits, the composition and contents of serum lipids and BAs were detected by Liquid Chromatograph-Mass Spectrometry, the mRNA levels of hepatic BAs homeostasis-related genes were detected by RT-qPCR, and microbiological diversity in ileum was analyzed by 16S rDNA sequencing. Results: The results showed that the significant changes including 29 lipids, 4 BAs (23-nor-deoxycholic acid, ursodeoxycholic acid, 7-ketodeoxycholic acid and cholic acid), 2 BA transporters (Mrp2 and Oatp1b2) and 8 GMs between MCD and DMY groups. Among them, DMY treatment significantly down-regulated 21 lipids, 4 BAs mentioned above, the ratio of Firmicutes/Bacteroidota and the abundance of Erysipelotrichaceae, Faecalibacuium, significantly up-regulated 8 lipids and 5 GMs (Verrucomicrobiota, Bacteroidota, Actinobacteria, Akkermansiaceae and Akkermansia). Conclusions: The results suggested that DMY may alleviate MCD diet-induced NASH through decreasing the serum levels of toxic BAs which regulated by liver Oatp1b2 and Mrp2, regulating the metabolism of related lipids, and up-regulating intestinal probiotics (Actinobacteria and Verrucomicrobiota at the phylum level; Akkermansiaceae at the family level; Akkermansiaat at the genus level) and inhibiting intestinal harmful bacteria (Firmicutes at the phylum level; Erysipelotrichaceae at the family level; Faecalibaculum at the genus level). [ABSTRACT FROM AUTHOR]

Introduction: Central retinal artery occlusion (CRAO) is a common cause of blindness and visual morbidity. In the majority of cases, it is related to thrombotic embolism. Nevertheless, the role of inherited or acquired thrombophilic risk factors in CRAO pathogenesis has not been comprehensively studied. Methods: In 126 CRAO patients (66 [52.4%] men, median age 55 [range: 18–80] years) and 107 matched controls (56 [52.3%] men, median age 53 [range: 34–78] years) we evaluated classical atherosclerotic risk factors, including serum lipid profile and glucose level, analyzed intima-media complex thickness (IMT) of external carotid arteries, and performed transthoracic echocardiography. Furthermore, we established the prevalence of inherited and acquired thrombophilic risk factors, such as factor V Leiden (FVL) and prothrombin 20210 G/A genetic variants, plasma activity of factor (F) VIII, protein C and antithrombin activity, and free protein S levels. We also assessed the presence of antiphospholipid antibodies (APLA) and evaluated blood homocysteine in all enrolled subjects. Additionally, we estimated the occurrence of Val34Leu polymorphism of the A subunit of coagulation factor XIII (FXIII-A) in both groups as a potential thrombosis-protecting factor. Results: Among traditional atherosclerotic risk components, obesity/overweight and hypercholesterolemia were the most common in the CRAO group and occurred in 103 (81.7%) and 85 (67.5%) patients, respectively. CRAO patients also had elevated IMT and altered echocardiographic parameters, indicating diastolic cardiac dysfunction. In thrombophilia investigations, at least one laboratory risk factor occurred in 72.2% (n = 91) of CRAO patients, with APLA as the most frequent, detected in 38.1% (n = 48) of them (almost seven times more frequent than in controls, p < 0.001). Deficiencies in protein C activity and free protein S levels were also common in the CRAO group, reported in 17.5% (n = 22) and 19.8% (n = 25) of patients, respectively. Interestingly, among two analyzed prothrombotic genetic variants, only the FVL was related to CRAO, with the allelic frequency 2.4 times more prevalent than in controls (p = 0.044). Finally, the CRAO group was characterized by hyperhomocysteinemia, almost twice as common as in controls (p = 0.026). Antithrombin deficiency, elevated FVIII, and FXIII-A Val34Leu polymorphism were not associated with CRAO. Conclusions: Our findings suggest that thrombophilia plays a vital role in the pathogenesis of CRAO. Thus, proper laboratory screening should be considered in the primary and secondary prevention of those episodes, with implementing appropriate therapy as needed. [ABSTRACT FROM AUTHOR]

Objective: Diabetes is the most common metabolic disorder that leads to various complications, and among these complications, disruption in the lipid profile and serum uric acid (SUA) is one of the significant cases that can lead to the deterioration of the health status of patients with diabetes. So, we aimed to evaluate the level of SUA and lipid profiles in patients with diabetes. A total of 230 patients with diabetes who were admitted to Razi Hospital, Rasht, Iran, were enrolled in this study. Demographical data and clinical characteristics of the patients include gender, body mass index (BMI), duration of diabetes, history of smoking, FBS, HbA1c, SUA, Creatinine (Cr), Cholesterol (Chol), low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides (TG), retinopathy, hypertension, ischemic heart disease (IHD), and microalbuminuria were recorded. All data were analyzed using the SPSS version 21 by a significant level < 0.05. Result: According to our results, 70 were male, and 160 were female, with a mean age of 57.36 ± 8.05 years and a mean BMI of 28.10 ± 4.62. The most frequent comorbidities were hypertension, 67%. The serum level of FBS, HBA1c, SUA, Cr, Chol, LDL, HDL, and TG were 191.47 ± 71.66 mg/dL, 7.94 ± 1.21 mg/dL, 5.65 ± 1.95 mg/dL, 0.94 ± 0.16 mg/dL, 167.28 ± 45.22 mg/dL, 95.91 ± 37.03 mg/dL, 39.78 ± 10.44 mg/dL, and 186.75 ± 76.65 mg/dL, respectively. Only UA had a significant relationship with TG level (P < 0.05). [ABSTRACT FROM AUTHOR]

Background: Extensive population growth and climate change accelerate the search for alternative ways of plant-based biomass, biofuel and feed production. Here, we focus on hitherto unknow, new promising cold-stimulated function of phospholipid:diacylglycerol acyltransferase1 (PDAT1) – an enzyme catalyzing the last step of triacylglycerol (TAG) biosynthesis. Result: Overexpression of AtPDAT1 boosted seed yield by 160% in Arabidopsis plants exposed to long-term cold compared to standard conditions. Such seeds increased both their weight and acyl-lipids content. This work also elucidates PDAT1's role in leaves, which was previously unclear. Aerial parts of AtPDAT1-overexpressing plants were characterized by accelerated growth at early and vegetative stages of development and by biomass weighing three times more than control. Overexpression of PDAT1 increased the expression of SUGAR-DEPENDENT1 (SDP1) TAG lipase and enhanced lipid remodeling, driving lipid turnover and influencing biomass increment. This effect was especially pronounced in cold conditions, where the elevated synergistic expression of PDAT1 and SDP1 resulted in double biomass increase compared to standard conditions. Elevated phospholipid remodeling also enhanced autophagy flux in AtPDAT1-overexpresing lines subjected to cold, despite the overall diminished autophagy intensity in cold conditions. Conclusions: Our data suggest that PDAT1 promotes greater vitality in cold-exposed plants, stimulates their longevity and boosts oilseed oil production at low temperature. [ABSTRACT FROM AUTHOR]

Background: There is conflicting evidence on the relationship between dietary choline and betaine with metabolic markers and anthropometric characteristics. The aim of this study is to investigate the relationship between the interaction effects of dietary choline and betaine and physical activity (PA) on circulating creatine kinase (CK), metabolic and glycemic markers, and anthropometric characteristics in active youth. Methods: In this cross-sectional study, data were collected from 120 to 18 to 35-year-old people. The food frequency questionnaire was used to assess dietary data; United States Department of Agriculture website was used to calculate choline and betaine in foods. CK, fasting blood sugar (FBS) and lipid profile markers were measured with ELISA kits. Low-density lipoprotein, and insulin sensitivity markers were calculated. Sociodemographic status, physical activity, and anthropometric characteristics were assessed based on a valid and reliable method. Analysis of co-variance (ANCOVA) tests adjusted for sex, PA, age, energy, and body mass index were used. Results: Increasing dietary betaine and total choline and betaine was positively related to weight, waist-to-hip ratio, fat-free mass and bone mass (P < 0.05). Increasing dietary betaine lowered total cholesterol (P = 0.032) and increased high density lipoprotein (HDL) (P = 0.049). The interaction effect of dietary choline and physical activity improved insulin resistance (P < 0.05). As well as dietary betaine interacted with physical activity increased HDL (P = 0.049). In addition, dietary total choline and betaine interacted with physical activity decreased FBS (P = 0.047). Conclusions: In general, increasing dietary choline and betaine along with moderate and high physical activity improved insulin resistance, increased HDL, and lowered FBS in the higher tertiles of dietary choline and betaine. [ABSTRACT FROM AUTHOR]

Background: Oxidative stress (OS) is associated with a variety of non-communicable diseases, including MetS, diabetes mellitus, metabolic syndrome, and cardiovascular disease through increased production of reactive oxygen species (ROS) and impairment of antioxidant defense mechanisms. Antioxidants can protect cells against free radical damage, so it seems important to determine the relationship between the quality of dietary antioxidants intake and chronic diseases. The Dietary Antioxidant Quality Score (DAQS) is obtained by adding the daily intake of known dietary vitamins and minerals, including selenium, zinc, vitamin A, vitamin C, and vitamin E, compared to the recommended daily intake (RDI). Therefore, this study aims to determine the relationship between DAQS, serum lipids, markers of glucose homeostasis, blood pressure and anthropometric features among obese adults. Methods: In the present cross-sectional study, 338 individuals who were obese (BMI ≥ 30 kg/m2) aged 20-50 years were recruited from Tabriz and Tehran, Iran. A validated semi-quantitative Food Frequency Questionnaire (FFQ) with 168 food items was used to quantify dietary consumption; accordingly, DAQS was computed. Blood biomarkers were measured using enzyme-linked immunosorbent assay (ELISA) kits. A standard mercury sphygmomanometer was used to assess blood pressure, and bioelectrical impedance analysis (BIA) was performed to determine body composition. The association between the DAQS tertiles and biochemical variables was investigated using multinomial logistic regression. Results: Participants in the highest tertile of DAQS have a lower diastolic blood pressure (DBP) values in all of the adjusted models [odds ratio (OR) = 0.920; confidence interval (CI)= 0.852-0.993, P-value = 0.03] in the analysis of co-variance (ANCOVA) model. Similarly, subjects at the second tertile of DAQS had lower DBP compared with the first tertile in age and sex-adjusted model [OR= 0.937; CI= 0.882-0.997]. There was no statistically significant difference for other metabolic parameters in different DAQS tertiles. Conclusion: According to our findings, higher DAQS was associated with lower DBP among obese adults with obesity in two major cities of Iran (Tehran and Tabriz). Other studies with interventional design are needed to better elucidate these associations and underlying mechanisms. [ABSTRACT FROM AUTHOR]

Background: Yarrowia lipolytica is a well-studied oleaginous yeast known for its ability to accumulate and store intracellular lipids, while growing on diverse, non-conventional substrates. Amongst them, crude glycerol, a low-cost by-product of the biodiesel industry, appears to be an interesting option for scaling up a sustainable single-cell oil production process. Adaptive laboratory evolution (ALE) is a powerful tool to force metabolic adaptations endowing tolerance to stressful environmental conditions, generating superior phenotypes with industrial relevance. Results: Y. lipolytica MUCL 28849 underwent ALE in a synthetic medium with increasing concentration of pure or crude glycerol as a stressing factor (9–20% v/v) for 520 generations. In one case of pure glycerol, chemical mutagenesis with ethyl methanesulfonate (EMS) was applied prior to ALE. Growth profile, biomass production and lipid content of 660 evolved strains (EVS), revealed 5 superior isolates; exhibiting from 1.9 to 3.6-fold increase of dry biomass and from 1.1 to 1.6-fold increase of lipid concentration compared to the parental strain, when grown in 15% v/v crude glycerol. NGS for differential gene expression analysis, showed induced expression in all EVS affecting nucleosomal structure and regulation of transcription. As strains differentiated, further changes accumulated in membrane transport and protein transport processes. Genes involved in glycerol catabolism and triacylglycerol biosynthesis were overexpressed in two EVS. Mismatches and gaps in the expressed sequences identified altered splicing and mutations in the EVS, with most of them, affecting different components of septin ring formation in the budding process. The selected YLE155 EVS, used for scale-up cultivation in a 3L benchtop bioreactor with 20% v/v crude glycerol, achieved extended exponential phase, twofold increase of dry biomass and lipid yields at 48 h, while citric acid secretion and glycerol consumption rates were 40% and 50% lower, respectively, compared to the parental strain, after 24 h of cultivation. Conclusion: ALE and EMS-ALE under increasing concentrations of pure or crude glycerol generated novel Y. lipolytica strains with enhanced biomass and lipid content. Differential gene expression analysis and scale-up of YLE155, illustrated the potential of the evolved strains to serve as suitable "chassis" for rational engineering approaches towards both increased lipid accumulation, and production of high-added value compounds, through efficient utilization of crude glycerol. [ABSTRACT FROM AUTHOR]

The current study is focused on the lipid extract of microalgae; Pectinodesmus strain PHM3 and its general analysis in terms of chemical contents. Combinations of both chemical and mechanistic approaches were applied to obtain the maximum yield of lipids which was recorded to be 23% per gram through continuous agitation using Folch solution. The extraction methods used in this study included: Bligh and Dyers method, Continuous agitation method, Extraction using Soxhlet and Acid base extraction method. Lipid quantification of ethanol and Folch solution lipid extract was performed through gravimetric methods and qualification was done through Fourier Transmission Infrared Spectroscopy (FTIR) and Gas Chromatographymass spectrometry (GC-MS). Phytochemical analysis identified other compounds in ethanol extract and the results confirmed the presence of steroids, coumarins, tannins, phenols and carbohydrates. Transesterification of lipids showed 7% per gram dry weight yield of Pectinodesmus PHM3. GC-MS studies of extracted biodiesel suggested that 72% of biofuels was in the form of dipropyl ether, ethyl butyl ethers, methyl butyl ether and propyl butyl ether. Lipid processing of acid-base extract showed that oily nature of lipid shifted to a more precipitated form which is a common observation when mixture of lipids is converted to phosphatides. [ABSTRACT FROM AUTHOR]

It is reported that pulmonary fibrosis has become one of the major long-term complications of COVID-19, even in asymptomatic individuals. Currently, despite the best efforts of the global medical community, there are no treatments for COVID-induced pulmonary fibrosis. Recently, inhalable nanocarriers have received more attention due to their ability to improve the solubility of insoluble drugs, penetrate biological barriers of the lungs and target fibrotic tissues in the lungs. The inhalation route has many advantages as a non-invasive method of administration and the local delivery of anti-fibrosis agents to fibrotic tissues like direct to the lesion from the respiratory system, high delivery efficiency, low systemic toxicity, low therapeutic dose and more stable dosage forms. In addition, the lung has low biometabolic enzyme activity and no hepatic first-pass effect, so the drug is rapidly absorbed after pulmonary administration, which can significantly improve the bioavailability of the drug. This paper summary the pathogenesis and current treatment of pulmonary fibrosis and reviews various inhalable systems for drug delivery in the treatment of pulmonary fibrosis, including lipid-based nanocarriers, nanovesicles, polymeric nanocarriers, protein nanocarriers, nanosuspensions, nanoparticles, gold nanoparticles and hydrogel, which provides a theoretical basis for finding new strategies for the treatment of pulmonary fibrosis and clinical rational drug use. [ABSTRACT FROM AUTHOR]

Background: Atherosclerosis is now the main cause of cardiac-cerebral vascular diseases around the world. Disturbances in lipid metabolism have an essential role in the development and progression of atherosclerosis. Thus, we aimed to investigate lipid metabolism-related molecular clusters and develop a diagnostic model for atherosclerosis. Methods: First, we used the GSE100927 and GSE43292 datasets to screen differentially expressed lipid metabolism-related genes (LMRGs). Subsequent enrichment analysis of these key genes was performed using the Metascape database. Using 101 atherosclerosis samples, we investigated the LMRG-based molecular clusters and the corresponding immune cell infiltration. After that, a diagnostic model for atherosclerosis was constructed using the least absolute shrinkage and selection operator (LASSO) and multivariate logistic regression. Finally, a series of bioinformatics techniques, including CIBERSORT, gene set variation analysis, and single-cell data analysis, were used to analyze the potential mechanisms of the model genes in atherosclerosis. Results: A total of 29 LMRGs were found to be differentially expressed between atherosclerosis and normal samples. Functional and DisGeNET enrichment analyses indicated that 29 LMRGs are primarily engaged in cholesterol and lipid metabolism, the PPAR signaling pathway, and regulation of the inflammatory response and are also closely associated with atherosclerotic lesions. Two LMRG-related molecular clusters with significant biological functional differences are defined in atherosclerosis. A three-gene diagnostic model containing ADCY7, SCD, and CD36 was subsequently constructed. Receiver operating characteristic curves, decision curves, and an external validation dataset showed that our model exhibits good predictive performance. In addition, three model genes were found to be closely associated with immune cell infiltration, especially macrophage infiltration. Conclusions: Our study comprehensively highlighted the intricate association between lipid metabolism and atherosclerosis and created a three-gene model for future clinical diagnosis. [ABSTRACT FROM AUTHOR]

Background: One of the most prevalent sleep disorders affecting the individual's daily life is obstructive sleep apnea (OSA), for which obesity is a major risk factor. Several novel lipid indices have been suggested to have associations with OSA, among which visceral adiposity index (VAI), atherogenic index of plasma (AIP), and lipid accumulation product (LAP) are the most important ones. Herein, the current study aimed to systematically investigate the association between these indices and OSA. Methods: Four international databases, including PubMed, Scopus, the Web of Science, and Embase were searched in order to find relevant studies that investigated LAP, VAI, or AIP in OSA and compared them with non-OSA cases or within different severities of OSA. Random-effect meta-analysis was used to generate the standardized mean difference (SMD) and 95% confidence interval (CI) of the difference in lipid indices between OSA and non-OSA cases. Moreover, the pooled area under the receiver operating characteristic curves (AUCs) observed in individual studies for diagnosis of OSA based on these lipid indices were calculated by random-effect meta-analysis. Results: Totally 14 original studies were included, comprised of 14,943 cases. AIP, LAP, and VAI were assessed in eight, five, and five studies, respectively. Overall, these lipid indices had acceptable diagnostic ability (AUC 0.70, 95% CI 0.67 to 073). Meta-analysis revealed that AIP was significantly higher in patients with OSA (SMD 0.71, 95% CI 0.45 to 0.97, P < 0.01). Moreover, AIP also increased in higher severities of OSA. Regarding LAP, a higher LAP was observed in OSA/patients with high risk for OSA rather than in controls/low risk for OSA (SMD 0.53, 95% CI 0.25 to 0.81, P < 0.01). VAI was also increased in OSA based on results from two studies. Conclusion: These findings suggest that composite lipid indices are increased in OSA. Also, these indices can have the potential beneficiary diagnostic and prognostic ability in OSA. Future studies can confirm these findings and enlighten the role of lipid indices in OSA. [ABSTRACT FROM AUTHOR]

Background: Breast cancer (BC) is the second most frequent type of cancer in the world and most common among women, configuring a major challenge to global health. BC is a complex and heterogeneous disease that can be subdivided into distinct tumor types based on the expression of molecular markers predicting patient outcomes and response to therapy. A growing number of studies have tried to expand the known markers by investigating the association of altered lipid metabolism with BC immune escape, progression, and metastasis. In this review, we describe the metabolic peculiarities of each BC subtype, understanding how this influences its aggressiveness and identifying whether these intrinsic vulnerabilities of each subtype can play a role in therapeutic management and may affect immune system cells in the tumor microenvironment. Conclusion: The evidence suggests so far that when changes occur in lipid pathways, it can affect the availability of structural lipids for membrane synthesis, lipid synthesis, and degradation that contribute to energy homeostasis and cell signaling functions. These findings will guide the next steps on the path to understanding the mechanisms underlying how lipids alterations are related to disparities in chemotherapeutic response and immune escape in BC. 7vDCpP8sT_C9HCxHHmwBCf Video Abstract [ABSTRACT FROM AUTHOR]

Background: Dysregulation of lipid metabolism is closely associated with cancer progression. The study aimed to establish a prognostic model to predict distant metastasis-free survival (DMFS) in patients with nasopharyngeal carcinoma (NPC), based on lipidomics. Methods: The plasma lipid profiles of 179 patients with locoregionally advanced NPC (LANPC) were measured and quantified using widely targeted quantitative lipidomics. Then, patients were randomly split into the training (125 patients, 69.8%) and validation (54 patients, 30.2%) sets. To identify distant metastasis-associated lipids, univariate Cox regression was applied to the training set (P < 0.05). A deep survival method called DeepSurv was employed to develop a proposed model based on significant lipid species (P < 0.01) and clinical biomarkers to predict DMFS. Concordance index and receiver operating curve analyses were performed to assess model effectiveness. The study also explored the potential role of lipid alterations in the prognosis of NPC. Results: Forty lipids were recognized as distant metastasis-associated (P < 0.05) by univariate Cox regression. The concordance indices of the proposed model were 0.764 (95% confidence interval (CI), 0.682–0.846) and 0.760 (95% CI, 0.649–0.871) in the training and validation sets, respectively. High-risk patients had poorer 5-year DMFS compared with low-risk patients (Hazard ratio, 26.18; 95% CI, 3.52–194.80; P < 0.0001). Moreover, the six lipids were significantly correlated with immunity- and inflammation-associated biomarkers and were mainly enriched in metabolic pathways. Conclusions: Widely targeted quantitative lipidomics reveals plasma lipid predictors for LANPC, the prognostic model based on that demonstrated superior performance in predicting metastasis in LANPC patients. [ABSTRACT FROM AUTHOR]

Background: Chemotherapy-induced neuropathic pain (CIPN) describes a pathological pain state that occurs dose-dependently as a side effect and can limit or even impede an effective cancer therapy. Unfortunately, current treatment possibilities for CIPN are remarkably confined and mostly inadequate as CIPN therapeutics themselves consist of low effectiveness and may induce severe side effects, pointing out CIPN as pathological entity with an emerging need for novel treatment targets. Here, we investigated whether the novel and highly specific FKBP51 inhibitor SAFit2 reduces paclitaxel-induced neuropathic pain. Methods: In this study, we used a well-established multiple low-dose paclitaxel model to investigate analgesic and anti-inflammatory properties of SAFit2. For this purpose, the behavior of the mice was recorded over 14 days and the mouse tissue was then analyzed using biochemical methods. Results: Here, we show that SAFit2 is capable to reduce paclitaxel-induced mechanical hypersensitivity in mice. In addition, we detected that SAFit2 shifts lipid levels in nervous tissue toward an anti-inflammatory and pro-resolving lipid profile that counteracts peripheral sensitization after paclitaxel treatment. Furthermore, SAFit2 reduced the activation of astrocytes and microglia in the spinal cord as well as the levels of pain-mediating chemokines. Its treatment also increased anti-inflammatory cytokines levels in neuronal tissues, ultimately leading to a resolution of neuroinflammation. Conclusions: In summary, SAFit2 shows antihyperalgesic properties as it ameliorates paclitaxel-induced neuropathic pain by reducing peripheral sensitization and resolving neuroinflammation. Therefore, we consider SAFit2 as a potential novel drug candidate for the treatment of paclitaxel-induced neuropathic pain. [ABSTRACT FROM AUTHOR]

Background: Recent evidence has revealed that circulating coagulation factor prekallikrein (PK), an important part of the kallikrein-kinin system, regulates cholesterol metabolism, but the association between serum PK and lipid levels is unclear. Methods: This cross-sectional study included 256 subjects (aged from 1 month to 90 years) who underwent physical examinations at the First People's Hospital of Huaihua, China. After overnight fasting, serum was collected for PK and lipid testing. Spearman correlation analysis and multivariable logistic regression analysis were used to analyze the association of PK level with lipid levels and the likelihood risk of hyperlipidemia. The possible threshold value of PK was calculated according to the receiver operating characteristic (ROC) curve. Results: The median serum PK level was 280.9 µg/mL (IQR 168.0, 377.0), and this level changed with age but not sex. The serum PK level was positively correlated with the serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) levels. A nonlinear relationship was observed between serum PK and high-density lipoprotein cholesterol (HDL-C) levels. The serum PK level was positively correlated with HDL-C when its level was lower than 240 µg/mL and negatively correlated with HDL-C when its level was higher than 240 µg/mL. The regression analysis demonstrated that an elevated serum PK level was significantly associated with the likelihood risk of hypercholesterolemia and hypertriglyceridemia. The ROC curve showed that the possible threshold values of serum PK for hypercholesterolemia and hypertriglyceridemia occurrences were 344.9 µg/mL and 305.7 µg/mL, respectively. Conclusions: Elevated serum PK levels were significantly associated with the likelihood of hypercholesterolemia and hypertriglyceridemia, and the possible threshold values of PK levels were 344.9 µg/mL and 305.70 µg/mL, respectively, suggesting that higher PK levels may be a risk factor for cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Familial hypercholesterolaemia (FH) is a frequent genetic disorder characterised by high plasma levels of total and LDL-cholesterol and premature atherosclerosis. If left untreated, affected subjects have a high risk of cardiovascular disease, as they are exposed to very high levels of LDL-cholesterol from birth. Healthy dietary habits and lifestyle are the first treatment option and, if started from childhood, represent a milestone in the prevention of atherosclerotic disease, both as a starting point and in combination with drug therapy. In this work, based on the main consensus documents available so far, we have evaluated the most up-to-date indications of the dietetic-nutritional intervention for the treatment of FH, delving into the peculiar aspects of the diet of the child/adolescent affected by FH. After an analysis of the macro- and micronutrients and the most common dietary patterns currently recommended, we highlighted some practical aspects, some frequent errors and some risks we could fall into when dealing with paediatric nutritional treatment. In conclusion, the dietary intervention for the child/adolescent with FH is a complex task, that should be individualised and tailored taking into account, first of all, the nutritional adequacy for growth and development, but also the multiple aspects linked to the child/adolescent's age, tastes and preferences, the family they belong to, the socio-economic context and the Country they live in. [ABSTRACT FROM AUTHOR]

Hepatic lipid droplets (LDs) are implicated in ectopic lipid accumulation. The core of LDs, triacylglycerol (TAG), is synthesized from the esterification of fatty acids to a glycerol-3-phosphate (G-3-P) backbone. Albumin transports plasma free fatty acids, and previously albumin knockout (Alb−/−) mice were shown to exhibit lower hepatic TAG levels than wildtype (WT). Exercise is a beneficial strategy to alter hepatic metabolism, but its impacts on reducing hepatic lipids are far from satisfactory. The aim of this study was to investigate the combined effect of albumin deficiency and acute exercise on hepatic LDs. Eight-week-old male Alb−/− and WT mice were divided into sedentary and exercise groups. Exercised mice performed a 30-min high-intensity exercise bout. Results showed that sedentary Alb−/− mice had smaller hepatic LDs (P < 0.0001), associated with mitochondria, while WT mice exhibited larger LDs, surrounded by glycogen granules. Following acute exercise, hepatic LDs in Alb−/− mice reduced by 40% in size, while in WT increased by 14% (P < 0.0001). The maintenance of WT hepatic LDs was associated with elevated G-3-P level (P < 0.05), potentially derived from glycogen (R = -0.32, %change in glycogen versus LD content, P < 0.05). The reduction in Alb−/− mice LDs after exercise was possibly due to their low glycogen level. In conclusion, Alb−/− mice exhibited an enhanced capacity for reducing hepatic LD size and content in response to exercise. These findings suggest that modulating albumin's functions combined with exercise could be a potential strategy to reduce ectopic lipid deposition in the liver. [ABSTRACT FROM AUTHOR]

Background: Light is a key regulatory factor for photosynthesis and metabolism of microalgae. The diatom Phaeodactylum tricornutum is capable of exhibiting metabolic flexibility in response to light fluctuations. However, the metabolic switching and underlying molecular mechanisms upon illumination transitions remain poorly understood for this industrially relevant marine alga. To address these, the physiochemical and molecular responses of P. tricornutum upon high light (HL) and recovery (HLR) were probed. Results: Upon HL, P. tricornutum exhibited quick responses, including decreases in cell division, major light harvesting pigments (e.g., chlorophyll a, β-carotene, and fucoxanthin), chloroplastidic membrane lipids (e.g., monogalactosyldiacylglycerol, digalactosyldiacylglycerol, and sulfoquinovosyldiacylglycerol), and long-chain polyunsaturated fatty acids (e.g., C20:5), as well as increases in carbohydrates and neutral lipids particularly triacylglycerol. During HLR stage when the stress was removed, these physiochemical phenotypes were generally recovered, indicative of a rapid and reversible changes of P. tricornutum to cope with illumination transitions for survival and growth. Through the integrated analysis with time-resolved transcriptomics, we revealed the transcriptional control of photosynthesis and carbon metabolism in P. tricornutum responding to HL, which could be reversed more or less during the HLR stage. Furthermore, we highlighted key enzymes involved in carotenoid biosynthesis and lipid metabolism of P. tricornutum and identified monooxygenases putatively responsible for catalyzing the ketolation step towards fucoxanthin synthesis from neoxanthin. Conclusions: The detailed profiling of physiochemical and transcriptional responses of P. tricornutum to HL-HLR treatments advances our understanding on the adaption of the alga to illumination transitions and provides new insights into engineering of the alga for improved production of value-added carotenoids and lipids. [ABSTRACT FROM AUTHOR]

Background: Long-term childhood cancer survivors (CCS) are at high risk of having dyslipidemia including low high density lipoprotein cholesterol (HDL-C). However, little is known about the prevalence of low HDL-C and the impact of therapy exposure on HDL composition early after treatment is terminated. Methods: This associative study included 50 children and adolescents who had completed their cancer treatments (< 4 years). Clinical characteristics (demographic, diagnosis, treatment, anthropometric parameters), fasting plasma lipids, apoliporoteins (Apo) A-I and composition of HDL fractions (HDL2 and HDL3) were assessed. Data were stratified according to the presence of dyslipidemia and median doses of therapeutic agents and compared using Fisher exact or Mann–Whitney tests. Univariate binary logistic regression analyses were carried out to evaluate the associations between the clinical and biochemical characteristics and having low HDL-C. Composition of HDL2 and HDL3 particles was assessed in a sub-group of 15 patients and compared to 15 age- and sex-matched healthy controls using Wilcoxon paired test. Results: Of the 50 pediatric cancer patients included in this study (mean age: 11.30 ± 0.72 y; mean time since end of treatment: 1.47 ± 0.12 y; male: 38%), 8 had low HDL-C (16%), all of which were adolescent at diagnosis. Higher doses of doxorubicin were associated with lower HDL-C and Apo A-I levels. In hypertriglyceridemic patients and compared to normolipidemics, triglycerides (TG) content was greater in HDL2 and HDL3 fractions whereas esterified cholesterol (EC) content was lower in HDL2. Enrich TG content of HDL3 and lower EC of HDL2 was found in patients exposed to ≥ 90 mg/m2 doxorubicin. Factors positively associated with the risk of having low HDL-C were age, being overweight or obese and exposure to doxorubicin ≥ 90 mg/m2. Compared to healthy controls, a sub-group of 15 patients showed higher TG and free cholesterol (FC) content of HDL2 and HDL3 and lower EC content in HDL3. Conclusions: Overall, we found abnormalities in HDL-C and Apo A-I levels and in HDL composition early after pediatric cancer treatment that are influenced by age, overweight or obesity status and exposure to doxorubicin. [ABSTRACT FROM AUTHOR]

Background: With the urgent need to reduce carbon emissions, and the dwindling reserves of easily exploitable fossil fuel, microalgae-based biofuels that can be used for transport systems and CO2 abatement have attracted great attention worldwide in recent years. One useful characteristic of microalgae is their ability to accumulate high levels of lipid content, in particular under conditions of nitrogen deprivation, with numerous species identified so far. However, a trade-off between levels of lipid accumulation and biomass productivity hinders the commercial applicability of lipids from microalgae. Here, we sequenced the genomes of Vischeria sp. CAUP H4302 and Vischeria stellata SAG 33.83, which can accumulate high content of lipids rich in nutraceutical fatty acids and with excellent biomass yield in nitrogen-limiting culture. Results: A whole-genome duplication (WGD) event was revealed in V. sp. CAUP H4302, which is a rare event in unicellular microalgae. Comparative genomic analyses showed that a battery of genes encoding pivotal enzymes involved in fatty acids and triacylglycerol biosynthesis, storage polysaccharide hydrolysis, and nitrogen and amino acid-related metabolisms are expanded in the genus Vischeria or only in V. sp. CAUP H4302. The most highlighted is the expansion of cyanate lyase genes in the genus Vischeria, which may enhance their detoxification ability against the toxic cyanate by decomposing cyanate to NH3 and CO2, especially under nitrogen-limiting conditions, resulting in better growth performance and sustained accumulation of biomass under the aforementioned stress conditions. Conclusions: This study presents a WGD event in microalgae, providing new insights into the genetic and regulatory mechanism underpinning hyper-accumulation of lipids and offering potentially valuable targets for future improvements in oleaginous microalgae by metabolic engineering. [ABSTRACT FROM AUTHOR]

Background: To investigate the effect of low-intensity pulsed ultrasound (LIPUS) combined with lipid microbubbles on the proliferation and bone regeneration of bone marrow mesenchymal stem cells (BMSCs) in poly (lactic-glycolic acid copolymer) (PLGA)/α-tricalcium phosphate (TCP) 3D-printed scaffolds. Methods: BMSCs were irradiated with different LIPUS parameters and microbubble concentrations, and the best acoustic excitation parameters were selected. The expression of type I collagen and the activity of alkaline phosphatase were detected. Alizarin red staining was used to evaluate the calcium salt production during osteogenic differentiation. Results: BMSCs proliferation was the most significant under the condition of 0.5% (v/v) lipid microbubble concentration, 2.0 MHz frequency, 0.3 W/cm2 sound intensity and 20% duty cycle. After 14 days, the type I collagen expression and alkaline phosphatase activity in the scaffold increased significantly compared to those in the control group, and alizarin red staining showed more calcium salt production during osteogenic differentiation. After 21 days, scanning electron microscopy experiments showed that osteogenesis was obvious in the PLGA/TCP scaffolds. Conclusion: LIPUS combined with lipid microbubbles on PLGA/TCP scaffolds can promote BMSCs growth and bone differentiation, which is expected to provide a new and effective method for the treatment of bone regeneration in tissue engineering. [ABSTRACT FROM AUTHOR]

Background: Poor ovarian responders (POR) are women undergoing in-vitro fertilization who respond poorly to ovarian stimulation, resulting in the retrieval of lower number of oocytes, and subsequently lower pregnancy rates. The follicular fluid (FF) provides a crucial microenvironment for the proper development of follicles and oocytes through tightly controlled metabolism and cell signaling. Androgens such as dehydroepiandrosterone (DHEA) have been proposed to alter the POR follicular microenvironment, but the impact DHEA imposes on the FF metabolome and cytokine profiles is unknown. Therefore, the objective of this study is to profile and identify metabolomic changes in the FF with DHEA supplementation in POR patients. Methods: FF samples collected from 52 POR patients who underwent IVF with DHEA supplementation (DHEA +) and without (DHEA-; controls) were analyzed using untargeted liquid chromatography-tandem mass spectrometry (LC–MS/MS) metabolomics and a large-scale multiplex suspension immunoassay covering 65 cytokines, chemokines and growth factors. Multivariate statistical modelling by partial least squares-discriminant regression (PLSR) analysis was performed for revealing metabolome-scale differences. Further, differential metabolite analysis between the two groups was performed by PLSR β-coefficient regression analysis and Student's t-test. Results: Untargeted metabolomics identified 118 FF metabolites of diverse chemistries and concentrations which spanned three orders of magnitude. They include metabolic products highly associated with ovarian function – amino acids for regulating pH and osmolarity, lipids such fatty acids and cholesterols for oocyte maturation, and glucocorticoids for ovarian steroidogenesis. Four metabolites, namely, glycerophosphocholine, linoleic acid, progesterone, and valine were significantly lower in DHEA + relative to DHEA- (p < 0.05–0.005). The area under the curves of progesterone glycerophosphocholine, linoleic acid and valine are 0.711, 0.730, 0.785 and 0.818 (p < 0.05–0.01). In DHEA + patients, progesterone positively correlated with IGF-1 (Pearson r: 0.6757, p < 0.01); glycerophosphocholine negatively correlated with AMH (Pearson r: -0.5815; p < 0.05); linoleic acid correlated with estradiol and IGF-1 (Pearson r: 0.7016 and 0.8203, respectively; p < 0.01 for both). In DHEA- patients, valine negatively correlated with serum-free testosterone (Pearson r: -0.8774; p < 0.0001). Using the large-scale immunoassay of 45 cytokines, we observed significantly lower MCP1, IFNγ, LIF and VEGF-D levels in DHEA + relative to DHEA. Conclusions: In POR patients, DHEA supplementation altered the FF metabolome and cytokine profile. The identified four FF metabolites that significantly changed with DHEA may provide information for titrating and monitoring individual DHEA supplementation. [ABSTRACT FROM AUTHOR]

Background: Non-specific lipid-transfer protein (nsLTP) is a pan-allergen in the plant world, and a cause of significant concern as food allergen in the Mediterranean area, due to its general heat- and acid-resistance and hence the risk of severe allergic reactions. Pru p 3, the peach nsLTP, is considered the primary sensitizer to this allergen family and this allergy is usually persistent. Allergen-free diet and acute treatment of manifestations are the main recognized management goals in food allergy. Main text: The role of immunotherapy for treating food allergy in adult patients is controversial, but immunotherapy for Pru p 3 could potentially represent a relevant therapeutic strategy. We systematically searched databases for studies assessing the role of immunotherapy Pru p 3 in food allergy. Overall, nine studies were included. Immunotherapy with Pru p 3 appears to be effective and with a good safety profile in both peach and LTP allergy for some foods, such as peanut, in both RCT and real-life studies. Conclusions: Immunotherapy with Pru p 3 is a possible treatment option for food allergy to the peach LTP in the Mediterranean area, although at present have not reached routinary clinical practice. Larger studies are needed to confirm these findings and identify predictive biomarkers. [ABSTRACT FROM AUTHOR]

Background: Rice (Oryza sativa) straw is a common waste product that represents a considerable amount of bound energy. This energy can be used for biogas production, but the rate and level of methane produced from rice straw is still low. To investigate the potential for an increased biogas production from rice straw, we have here utilized WRINKLED1 (WRI1), a plant AP2/ERF transcription factor, to increase triacylglycerol (TAG) biosynthesis in rice plants. Two forms of Arabidopsis thaliana WRI1 were evaluated by transient expression and stable transformation of rice plants, and transgenic plants were analyzed both for TAG levels and biogas production from straw. Results: Both full-length AtWRI1, and a truncated form lacking the initial 141 amino acids (including the N-terminal AP2 domain), increased fatty acid and TAG levels in vegetative and reproductive tissues of Indica rice. The stimulatory effect of the truncated AtWRI1 was significantly lower than that of the full-length protein, suggesting a role for the deleted AP2 domain in WRI1 activity. Full-length AtWRI1 increased TAG levels also in Japonica rice, indicating a conserved effect of WRI1 in rice lipid biosynthesis. The bio-methane production from rice straw was 20% higher in transformants than in the wild type. Moreover, a higher producing rate and final yield of methane was obtained for rice straw compared with rice husks, suggesting positive links between methane production and a high amount of fatty acids. Conclusions: Our results suggest that heterologous WRI1 expression in transgenic plants can be used to improve the metabolic potential for bioenergy purposes, in particular methane production. [ABSTRACT FROM AUTHOR]

Objective: Dysregulated lipid metabolism enhances the development and advancement of many cancers, including osteosarcoma (OS); however, the underlying mechanisms are still largely unknown. Therefore, this investigation aimed to elucidate novel potential lipid metabolism-related long non-coding RNAs (lncRNAs) that regulate OS development and provide novel signatures for its prognosis and precise treatment. Materials and methods: The GEO datasets (GSE12865 and GSE16091) were downloaded and analyzed using R software packages. Immunohistochemistry (IHC) was used to evaluate protein levels in OS tissues while real-time qPCR was used to measure lncRNA levels, and MTT assays were used to assess OS cell viability. Results: Two lipid metabolism-associated lncRNAs (LM-lncRNAs), small nucleolar RNA host gene 17 (SNHG17) and LINC00837, were identified as efficient and independent prognostic indicators for OS. In addition, further experiments confirmed that SNHG17 and LINC00837 were significantly elevated in OS tissues and cells than para-cancerous counterparts. Knockdown of SNHG17 and LINC00837 synergistically suppressed the viability of OS cells, whereas overexpression of the two lncRNAs promoted OS cell proliferation. Moreover, bioinformatics analysis was conducted to construct six novel SNHG17-microRNA-mRNA competing endogenous RNA (ceRNA) networks, and three lipid metabolism-associated genes (MIF, VDAC2, and CSNK2A2) were found to be abnormally upregulated in OS tissues, suggesting that they were potential effector genes of SNHG17. Conclusion: In summary, SNHG17 and LINC00837 were found to promote OS cell malignancy, suggesting their use as ideal biomarkers for OS prognosis and treatment. [ABSTRACT FROM AUTHOR]

Background: Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide, and is related to disturbed lipid metabolism and redox homeostasis. However, a definitive drug treatment has not been approved for this disease. Studies have found that electromagnetic fields (EMF) can ameliorate hepatic steatosis and oxidative stress. Nevertheless, the mechanism remains unclear. Methods: NAFLD models were established by feeding mice a high-fat diet. Simultaneously, EMF exposure is performed. The effects of the EMF on hepatic lipid deposition and oxidative stress were investigated. Additionally, the AMPK and Nrf2 pathways were analysed to confirm whether they were activated by the EMF. Results: Exposure to EMF decreased the body weight, liver weight and serum triglyceride (TG) levels and restrained the excessive hepatic lipid accumulation caused by feeding the HFD. The EMF boosted CaMKKβ protein expression, activated AMPK phosphorylation and suppressed mature SREBP-1c protein expression. Meanwhile, the activity of GSH-Px was enhanced following an increase in nuclear Nrf2 protein expression by PEMF. However, no change was observed in the activities of SOD and CAT. Consequently, EMF reduced hepatic reactive oxygen species (ROS) and MDA levels, which means that EMF relieved liver damage caused by oxidative stress in HFD-fed mice. Conclusions: EMF may activate the CaMKKβ/AMPK/SREBP-1c and Nrf2 pathways to control hepatic lipid deposition and oxidative stress. This investigation indicates that EMF may be a novel therapeutic method for NAFLD. [ABSTRACT FROM AUTHOR]

Background: Gut microbiota are involved in the onset and development of chronic intestinal inflammation. The recently described endocannabinoidome (eCBome), a diverse and complex system of bioactive lipid mediators, has been reported to play a role in various physio-pathological processes such as inflammation, immune responses and energy metabolism. The eCBome and the gut microbiome (miBIome) are closely linked and form the eCBome - miBIome axis, which may be of special relevance to colitis. Methods: Colitis was induced in conventionally raised (CR), antibiotic-treated (ABX) and germ-free (GF) mice with dinitrobenzene sulfonic acid (DNBS). Inflammation was assessed by Disease Activity Index (DAI) score, body weight change, colon weight-length ratio, myeloperoxidase (MPO) activity and cytokine gene expression. Colonic eCBome lipid mediator concentrations were measured by HPLC-MS /MS. Results: GF mice showed increased levels of anti-inflammatory eCBome lipids (LEA, OEA, DHEA and 13- HODE-EA) in the healthy state and higher MPO activity. DNBS elicited reduced inflammation in GF mice, having lower colon weight/length ratios and lower expression levels of Il1b, Il6, Tnfa and neutrophil markers compared to one or both of the other DNBS-treated groups. Il10 expression was also lower and the levels of several N-acyl ethanolamines and 13-HODE-EA levels were higher in DNBS-treated GF mice than in CR and ABX mice. The levels of these eCBome lipids negatively correlated with measures of colitis and inflammation. Conclusions: These results suggest that the depletion of the gut microbiota and subsequent differential development of the gut immune system in GF mice is followed by a compensatory effect on eCBome lipid mediators, which may explain, in part, the observed lower susceptibility of GF mice to develop DNBS-induced colitis. [ABSTRACT FROM AUTHOR]

Background: Arteriosclerosis and non-alcoholic fatty liver disease are major complications of diabetes mellitus. Hyperglycemia, insulin resistance, obesity, and metabolic syndrome are associated with the progression of these complications. Sodium-glucose transporter 2 inhibitors such as luseogliflozin are oral hypoglycemic agents that reduce glucose levels, induce loss of weight or body fat, and improve liver function. However, the effects of these agents on lipid profiles are unclear. Therefore, this study aimed to investigate these effects and their relationship with arteriosclerosis and non-alcoholic fatty liver disease. Methods: This single-center, single-arm, open-labeled prospective study enrolled 25 outpatients with type 2 diabetes mellitus who visited Minami Osaka Hospital. Laboratory tests and body measurements were performed at weeks 0 and 24. Luseogliflozin was started at 2.5 mg/day after breakfast, and data from weeks 0 and 24 were evaluated. There were no changes in the doses of other antidiabetic and dyslipidemia drugs a month prior to or during the study. Results: The patients showed significant reductions in the levels of triglycerides, remnant-like particle cholesterol, and triglyceride/high-density lipoprotein cholesterol ratio, along with significant increases in the levels of high-density lipoprotein cholesterol and apolipoprotein A-1. Alanine aminotransferase, γ-glutamyl transpeptidase, and the fatty liver index were significantly reduced. Conclusions: Luseogliflozin-induced changes in the lipid profile were related to the suppression or improvement of arteriosclerosis and liver function, respectively. Patients who received this drug also showed improvements in the levels of liver enzymes and reductions in the fatty liver index. Earlier use of luseogliflozin might prevent diabetic complications. Trial registration This study was registered in the University Hospital Medical Information Network Clinical Trial Registry (UMIN 000043595) on April 6th, 2021 [ABSTRACT FROM AUTHOR]

Background: Breast cancer is associated with alterations in lipid metabolism. The treatment of breast cancer can also affect serum lipid composition. The purpose of this study was the examination of serum fatty acids (FAs) profiles in breast cancer survivors to assess if the FA levels normalize. Methods: Serum levels of FAs were determined by gas chromatography–mass spectrometry in a group of breast cancer patients at baseline (before treatment, n = 28), at two follow-up visits at 12 months (n = 27) and 24 months (n = 19) after the breast cancer resection, and in the group of healthy controls (n = 25). Multivariate analysis was performed to assess how FA serum profile changes following treatment. Results: Breast cancer patients' serum FA profiles at follow-ups did not normalize to the levels of control group. The greatest differences were found for levels of branched-chain (BCFA), odd-chain (OCFA) and polyunsaturated (PUFAs) FAs, all of which were significantly increased 12 months after the surgery. Conclusions: After treatment for breast cancer, the patients' serum FA profile differs from the profile before treatment and from controls, especially 12 months after treatment. Some changes may be beneficial – increased BCFA and OCFA levels, and improved n-6/n-3 PUFA ratio. This may reflect lifestyle changes in breast cancer survivors and have an impact on the risk of recurrence. [ABSTRACT FROM AUTHOR]

Objective and design: In this cross-sectional study, evaluation of the association between four dietary patterns, nutrients and food intakes and an array of systemic inflammation biomarkers and lipid profile among 80 New Zealand postmenopausal women were conducted. Materials: Eighty postmenopausal women participated in the study. A validated food frequency questionnaire was used to collect nutrients and food intake. Four dietary patterns were identified by principal component analysis (PCA) and plasma samples collected for inflammatory biomarkers and lipid profile measures. Results: There were negative correlations between intake of dietary fibre, soluble and insoluble non-starch polysaccharides (NSP), vitamin C and niacin and with almost all the inflammatory markers for the whole group. Vegetables, tea/coffee and especially fruit intake were negatively correlated with the inflammatory biomarkers in the whole group. A high intake of Pattern 1 (potato, bread, and fruit pattern) was associated with a low risk of high interferon (IFN)-α2, IFN-λ, interleukin (IL)-6 and IL-8 levels while a high intake of Pattern 3 (fast-food pattern) was associated high risk of IFN-α2 levels. Multiple linear regression showed a negative correlation between Pattern 2 (soups and vegetables pattern) and levels of C-reactive protein (CRP) as well as ferritin. A positive association was observed between Pattern 3 (fast-food pattern) and CRP levels. Positive correlation was also observed between Pattern 2 and high-density lipoprotein (HDL) and total cholesterol (TC) levels, Pattern 4 (meat and vegetables pattern) was however negatively correlated with TC, low-density lipoprotein (LDL) and TC/HDL ratio. Conclusions: The result of this study reinforces the contribution and role of diet in modifying inflammation in postmenopausal women. [ABSTRACT FROM AUTHOR]

Background: The challenging rigorous management of hypercholesterolemia promotes referral to specialized units. This study explored the need, based on referral rate and cardiovascular (CV) risk factor control in patients evaluated for familial hypercholesterolemia (FH), for a lipid unit (LU). Methods: Over a four-year period, 340 referrals to our unit were analyzed to establish the lipid disorder referral rate. Moreover, 118 patients referred for potential FH during the period 2010–2018 (52.4 ± 13.9 years, 47.5% male, Caucasian, 26.3% obese, 33.1% smokers and 51.7% with some glycaemic alteration) were investigated. The Dutch Lipid Clinic Network (DLCN) score, type and dose of lipid-lowering drugs, lipid profile including lipoprotein (a) (Lp(a)) and the presence of plaques with carotid ultrasound (CU) were recorded. Results: Lipids represented 6.2% of referrals (38 patient-years) requiring a 2–3 h weekly monographic outpatient consultation. The potential FH sample displayed a DLCN score ≥ 6 in 78% and modifiable CV risk factors in 51%. Only 22% achieved tight disease control despite intensive treatment. The statin-ezetimibe combination treatment group achieved better goals (73.0% vs. 45.5%, P = 0.003), and the rosuvastatin group had a higher proportion of prediabetes (60.9% vs. 39.1%, P = 0.037). Neither CU plaque presence nor Lp(a) > 50 mg/dL was linked with established CV disease patients, but higher Lp(a) concentrations were detected between them (102.5 (26.3–145.8) vs. 25.0 (13.0–52.0) mg/dL, P = 0.012). Conclusions: The referral rate, degree of control, and proportion of modifiable CV risk factors in FH patients demonstrate the need for LU in our area as well as optimize control and treatment. [ABSTRACT FROM AUTHOR]

Background: Many commonly used drugs were evaluated as repurposed treatment options since the emergence of the COVID-19 pandemic. The benefit of lipid-lowering agents has been controversial in this regard. In this systematic review, we assessed the effect of these medications as adjunctive therapy in COVID-19 by the inclusion of randomized controlled trials (RCTs). Methods: We searched four international databases including PubMed, the Web of Science, Scopus, and Embase for RCTs in April 2023. The primary outcome was mortality, while other efficacy indices were considered secondary outcomes. In order to estimate the pooled effect size of the outcomes, considering the odds ratio (OR) or standardized mean difference (SMD) and 95% confidence interval (CI), random-effect meta-analyses was conducted. Results: Ten studies involving 2,167 COVID-19 patients using statins, omega-3 fatty acids, fenofibrate, PCSK9 inhibitors, and nicotinamide as intervention compared to control or placebo, were included. No significant difference was found in terms of mortality (OR 0.96, 95% CI 0.58 to 1.59, p-value = 0.86, I2 = 20.4%) or length of hospital stay (SMD -0.10, 95% CI -0.78 to 0.59, p-value = 0.78, I2 = 92.4%) by adding a statin to the standard of care. The trend was similar for fenofibrate and nicotinamide. PCSK9 inhibition, however, led to decreased mortality and an overall better prognosis. Omega-3 supplementation showed contradicting results in two trials, suggesting the need for further evaluation. Conclusion: Although some observational studies found improved outcomes in patients using lipid-lowering agents, our study found no benefit in adding statins, fenofibrate, or nicotinamide to COVID-19 treatment. On the other hand, PCSK9 inhibitors can be a good candidate for further assessment. Finally, there are major limitations in the use of omega-3 supplements in treating COVID-19 and more trials are warranted to evaluate this efficacy. [ABSTRACT FROM AUTHOR]

Background: Lipid metabolism disorder during pregnancy has been reported in women with gestational diabetes mellitus (GDM). However, controversy remains regarding the relationship between maternal changes in lipid profiles and perinatal outcomes. This study investigated the association between maternal lipid levels and adverse perinatal outcomes in women with GDM and non-GDM. Methods: In total, 1632 pregnant women with GDM and 9067 women with non-GDM who delivered between 2011–2021 were enrolled in this study. Serum samples were assayed for fasting total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) levels during the second and third trimesters of pregnancy. Adjusted odds ratios (AOR) and 95% confidence intervals (95% CI) were calculated via multivariable logistic regression analysis to determine the association of lipid levels with perinatal outcomes. Results: The serum TC, TG, LDL, and HDL levels in the third trimester were significantly higher than those in the second trimester (p < 0.001). Women with GDM had significantly higher levels of TC and TG in the second and third trimesters than those with non-GDM in the same trimesters, while HDL levels decreased in women with GDM (all p < 0.001). After adjusting for confounding factors by multivariate logistic regression, every mmol/L elevation in TG levels of women with GDM in second and third trimesters was associated with a higher risk of caesarean section (AOR = 1.241, 95% CI: 1.103–1.396, p < 0.001; AOR = 1.716, 95% CI: 1.556–1.921, p < 0.001), large for gestational age infants (LGA) (AOR = 1.419, 95% CI: 1.173–2.453, p = 0.001; AOR = 2.011, 95% CI: 1.673–2.735, p < 0.001), macrosomia (AOR = 1.220, 95% CI: 1.133–1.643, p = 0.005; AOR = 1.891, 95% CI: 1.322–2.519, p < 0.001), and neonatal unit admission (NUD; AOR = 1.781, 95% CI: 1.267–2.143, p < 0.001; AOR = 2.052, 95% CI: 1.811–2.432, p < 0.001) cesarean delivery (AOR = 1.423, 95% CI: 1.215–1.679, p < 0.001; AOR = 1.834, 95% CI: 1.453–2.019, p < 0.001), LGA (AOR = 1.593, 95% CI: 1.235–2.518, p = 0.004; AOR = 2.326, 95% CI: 1.728–2.914, p < 0.001), macrosomia (AOR = 1.346, 95% CI: 1.209–1.735, p = 0.006; AOR = 2.032, 95% CI: 1.503–2.627, p < 0.001), and neonatal unit admission (NUD) (AOR = 1.936, 95% CI: 1.453–2.546, p < 0.001; AOR = 1.993, 95% CI: 1.724–2.517, p < 0.001), which were higher than the relative risk of these perinatal outcomes in women with non-GDM. Additionally, every mmol/L increase in second and third-trimester HDL levels of women with GDM was associated with decreased risk of LGA(AOR = 0.421, 95% CI: 0.353–0.712, p = 0.007; AOR = 0.525, 95% CI: 0.319–0.832, p = 0.017) and NUD (AOR = 0.532, 95% CI: 0.327–0.773, p = 0.011; AOR = 0.319, 95% CI: 0.193–0.508, p < 0.001), and the risk reduction was not strong than that of women with GDM. Conclusions: Among women with GDM, high maternal TG in the second and third trimesters was independently associated with an increased risk of cesarean section, LGA, macrosomia, and NUD. High maternal HDL during the second and third trimesters was significantly associated with decreased risk of LGA and NUD. These associations were stronger than those in women with non-GDM, suggesting the importance of monitoring second and third-trimester lipid profiles in improving clinical outcomes, especially in GDM pregnancies. [ABSTRACT FROM AUTHOR]

Background: Psoriasis (PSO) is a skin disorder with systemic inflammation and high coronary artery disease risk. A distinct lipid phenotype occurs in psoriasis, which is characterized by high plasma triglycerides (TGs) with typically normal or even low LDL-C. The extent to which cholesterol on LDL subfractions, such as small dense LDL-C (sdLDL-C), are associated with vulnerable coronary plaque characteristics in PSO remains elusive. Methods: A recently developed equation for estimating sdLDL-C from the standard lipid panel was utilized in a PSO cohort (n = 200) with 4-year follow-up of 75 subjects. Coronary plaque burden was assessed by quantitative coronary computed tomography angiography (CCTA). Multivariate regression analyses were used for establishing associations and prognostic value of estimated sdLDL-C. Results: Estimated sdLDL-C was positively associated with non-calcified burden (NCB) and fibro-fatty burden (FFB), which remained significant after multivariate adjustment for NCB (β = 0.37; P = 0.050) and LDL-C adjustment for FFB (β = 0.29; P < 0.0001). Of note, total LDL-C calculated by the Friedewald equation was not able to capture these associations in the study cohort. Moreover, in the regression modelling estimated sdLDL-C was significantly predicting necrotic burden progression over 4 years follow-up (P = 0.015), whereas LDL-C did not. Finally, small LDL particles (S-LDLP) and small HDL particles (S-HDLP), along with large and medium TG-rich lipoproteins (TRLPs) had the most significant positive correlation with estimated sdLDL-C. Conclusions: Estimated sdLDL-C has a stronger association than LDL-C with high-risk features of coronary atherosclerotic plaques in psoriasis patients. Clinical trial registration: URL: https://www.clinicaltrials.gov. Unique identifiers: NCT01778569 [ABSTRACT FROM AUTHOR]

Background: Doravirine (DOR) is a newly approved antiretroviral belonging to the class of non-nucleoside reverse transcriptase inhibitors (NNRTI), well tolerated and leading to an improved lipid profile in antiretroviral experienced people living with HIV (PLWH). We aimed at evaluating if the lipid-lowering effect is linked to the drug class, using real-life data from the SCOLTA cohort. Methods: We compared the lipid profile modifications in experienced PLWH switching to a DOR-based regimen from rilpivirine or another NNRTI-based regimen or from an integrase strand transferase (INSTI)-based regimen. T0 and T1 were defined as the baseline and 6-month follow-up respectively. Data were collected at baseline and prospectively every six months and changes from baseline were compared using a multivariable linear model. Results: In 107 PLWH, enrolled in the SCOLTA DOR cohort, with undetectable HIV-RNA at baseline, 32.7% switched from RPV-based regimens (DOR1), 29.9% from other NNRTI-including regimens (DOR2) and 37.4% switched from INSTI-including regimens (DOR3). At T1, TC significantly decreased in DOR2 (-15 mg/dL) and DOR3 (-23 mg/dL), and significantly more in DOR3 than in DOR1 (-6 mg/dL) (p = 0.016). HDL-C declined in DOR2 (-2 mg/dL) whereas it increased in DOR1 (+ 3 mg/dL) (p = 0.042) and remained stable in DOR3. LDL-C significantly decreased from baseline in DOR2 (-12 mg/dL) and DOR3 (-22 mg/dL) and was different between DOR1 (-8 mg/dL) and DOR3 (p = 0.022). TC/HDL ratio showed a significant decline in the DOR3 group (-0.45), although similar to DOR1 (-0.23, p = 0.315) and DOR2 (-0.19, p = 0.254). Triglycerides did not noticeably change. ALT significantly decreased in PLWH with a baseline level > 40 UI/mL. Conclusions: PLWH on doravirine treatment showed different trends in blood lipids according to their previous regimen. In PLWH switching from RPV, minimal modifications were seen, whereas in those switching from other NNRTIs and from INSTI-including regimens, we observed an overall improvement in lipid profile, seemingly independent of the "statin effect" of TDF. [ABSTRACT FROM AUTHOR]

Background: Hypercholesterolemia is associated with tendon pathology, but the reasons underpinning this relationship are not well understood. Cholesterol can accumulate in the tendon non-collagenous matrix which may affect both global and local tissue mechanics. Changes to the local strain environment within tendon may have significant implications for mechanosensitive tenocytes. Here, we investigated the association between elevated blood cholesterol and presence of tendon lipids in the Achilles tendon. We expected lipids to be localised in the proteoglycan-rich inter-sub-tendon matrix (ISTM), therefore we also sought to examine the impact of this on the biomechanical and viscoelastic properties of the ISTM. Methods: The Achilles tendons of 32 young wild-type (SD) and 32 apolipoprotein E knock-out rats (ApoE−/−) were harvested at 15.6 ± 2.3 weeks of age. 32 specimens underwent histological examination to assess the distribution of lipids throughout sub-tendons and ISTM. The remaining specimens were prepared for biomechanical testing, where the ISTM between the gastrocnemius and soleus sub-tendons was subjected to shear load mechanical testing. A sub-set of tests were video recorded to enable a strain analysis. Results: ApoE−/− serum cholesterol was double that of SD rats (mean 2.25 vs. 1.10 mg/ml, p < 0.001) indicating a relatively mild hypercholesterolemia phenotype. Nonetheless, we found histological evidence of esterified lipids in the ISTM and unesterified lipids in the sub-tendons, although the location or intensity of staining was not appreciably different between rat strains. Despite a lack of observable histological differences in lipid content between groups, there were significant differences in the mechanical and viscoelastic behaviour of the Achilles sub-tendon matrix. Conclusion: Even slightly elevated cholesterol may result in subtle changes to tendon biomechanical properties and hence injury risk. The young age of our cohort and the mild phenotype of our ApoE−/− rats are likely to have limited our findings and so we also conclude that the ApoE−/− rat model is not well suited for investigating the biomechanical impact of tendon xanthomas on Achilles sub-tendon function. [ABSTRACT FROM AUTHOR]

Background: Pre-diabetes is a condition in which blood glucose levels are high but not as high as in diabetic patients. However, it can lead to diabetes, making it a serious global health issue. Previous studies have shown that the gut microbiome can affect insulin sensitivity and improve glucose management, which can reduce or delay the progression of pre-diabetes to type 2 diabetes mellitus. This study was designed to investigate the effects of probiotics on glycemic and lipid profile control in pre-diabetic patients. Methods: This randomized, double-blinded clinical trial was conducted on 70 pre-diabetic patients at the Ghaem Hospital, Mashhad University of Medical Sciences, Mashhad, Iran. Participants were divided into two groups, both of which received lifestyle modification training. One of the groups also received 500 mg/day probiotic capsules for three months, while the other group received a placebo. Before and after the three-month period, systolic and diastolic blood pressure, serum insulin level, hemoglobin A1c (HbA1c), fasting blood sugar (FBS), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglycerides (TG) were measured and compared using statistical tests to examine the effect of probiotics. Results: A total of 70 individuals participated in the trial, including 50 women (71.4%) and 20 men (28.6%), with an average age of 43.53 ± 8.54 years. At the end of the trial, the mean weight (P < 0.001), FBS (P < 0.001), HbA1c (P = 0.035), TG (P = 0.004), and LDL (P = 0.016) were significantly reduced in the intervention group, while their insulin level (P = 0.041) and HDL (P = 0.001) were significantly increased. However, mean systolic (P = 0.459) and diastolic blood pressure (P = 0.961) and insulin resistance (P = 0.235) did not show any significant difference in the intervention group from the beginning of the study. Conclusion: Our study showed that probiotic administration is effective in improving the glucose and lipid profile of pre-diabetic patients. However, it was not significantly different from the placebo. [ABSTRACT FROM AUTHOR]

Background: Presently, there is no consensus regarding the optimal serum uric acid (SUA) concentration for pediatric patients. Adenoid and tonsillar hypertrophy is considered to be closely associated with pediatric metabolic syndrome and cardiovascular risk and is a common condition in children admitted to the hospital. Therefore, we aimed to evaluate the relationship between SUA and dyslipidemia and propose a reference range for SUA concentration that is associated with a healthy lipid profile in hospitalized children with adenoid and tonsillar hypertrophy. Methods: Preoperative data from 4922 children admitted for elective adenoidectomy and/or tonsillectomy surgery due to adenoid and tonsillar hypertrophy were collected. SUA concentrations were scaled to standard deviation (SD), and SUA deviations were expressed as SD from the mean SUA of children without dyslipidemia. Results: The mean SUA concentration of the participants was 4.27 ± 1.01 mg/dL, and the prevalence of hyperuricemia was 1.6% when it was defined using an SUA of ≥ 7.0 mg/dL. Participants with dyslipidemia (856, 17.4%) had a higher prevalence of hyperuricemia (3.4% vs. 1.2%, P < 0.001) and higher SUA concentrations (4.51 ± 1.15 vs. 4.22 ± 0.97 mg/dL, P < 0.001) than those with ortholiposis. The circulating lipid status of participants with SUAs < 1 SD below the mean value for the participants with ortholiposis (range 1.80–3.28 mg/dL) was more normal. Each 1-SD increase in SUA was associated with a 27% increase in the risk of dyslipidemia (OR = 1.270, 95% CI, 1.185–1.361). Adjustment for a number of potential confounders reduced the strength of the relationship, but this remained significant (OR = 1.125, 95% CI, 1.042–1.215). The higher risk of dyslipidemia was maintained for participants with SUAs > 1 SD above the mean value of the participants with ortholiposis. Conclusions: SUA was independently associated with dyslipidemia in children with adenoid and tonsillar hypertrophy, and an SUA < 1 SD below the mean value for patients with ortholiposis was associated with a healthy lipid profile. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2DM), one of the main types of Noncommunicable diseases (NCDs), is a systemic inflammatory disease characterized by dysfunctional pancreatic β-cells and/or peripheral insulin resistance, resulting in impaired glucose and lipid metabolism. Genetic, metabolic, multiple lifestyle, and sociodemographic factors are known as related to high T2DM risk. Dietary lipids and lipid metabolism are significant metabolic modulators in T2DM and T2DM-related complications. Besides, accumulated evidence suggests that altered gut microbiota which plays an important role in the metabolic health of the host contributes significantly to T2DM involving impaired or improved glucose and lipid metabolism. At this point, dietary lipids may affect host physiology and health via interaction with the gut microbiota. Besides, increasing evidence in the literature suggests that lipidomics as novel parameters detected with holistic analytical techniques have important roles in the pathogenesis and progression of T2DM, through various mechanisms of action including gut-brain axis modulation. A better understanding of the roles of some nutrients and lipidomics in T2DM through gut microbiota interactions will help develop new strategies for the prevention and treatment of T2DM. However, this issue has not yet been entirely discussed in the literature. The present review provides up-to-date knowledge on the roles of dietary lipids and lipidomics in gut-brain axis in T2DM and some nutritional strategies in T2DM considering lipids- lipidomics and gut microbiota interactions are given. [ABSTRACT FROM AUTHOR]

Purpose: Diabetes mellitus (DM), a hyperglycemic condition, occurs due to the failure of insulin secretion and resistance. This study investigated the combined effects of exercise training and melatonin (Mel) on the function of heart tissue in diabetic rodent models. Methods: A systematic search was conducted in Embase, ProQuest, Cochrane library, Clinicaltrial.gov, WHO, Google Scholar, PubMed, Ovid, Scopus, Web of Science, Ongoing Trials Registers, and Conference Proceedings in July 2022 with no limit of date or language. All trials associated with the effect of Mel and exercise in diabetic rodent models were included. Of the 962 relevant publications, 58 studies met our inclusion criteria as follows; Mel and type 1 DM (16 studies), Mel and type 2 DM (6 studies), exercise and type 1 DM (24 studies), and exercise and type 2 DM (12 studies). Meta-analysis of the data was done using the Mantel Haenszel method. Results: In most of these studies, antioxidant status and oxidative stress, inflammatory response, apoptosis rate, lipid profiles, and glucose levels were monitored in diabetic heart tissue. According to our findings, both Mel and exercise can improve antioxidant capacity by activating antioxidant enzymes compared to the control diabetic groups (p < 0.05). The levels of pro-inflammatory cytokines, especially TNF-α were reduced in diabetic rodents after being treated with Mel and exercise. Apoptotic changes were diminished in diabetic rodents subjected to the Mel regime and exercise in which p53 levels and the activity of Caspases reached near normal levels (p < 0.05). Based on the data, both Mel and exercise can change the lipid profile in diabetic rodents, especially rats, and close it to near-to-control levels. Conclusion: These data showed that exercise and Mel can reduce the harmful effects of diabetic conditions on the heart through the regulation of lipid profile, antioxidant capacity, apoptosis, and inflammation. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2DM), one of the main types of Noncommunicable diseases (NCDs), is a systemic inflammatory disease characterized by dysfunctional pancreatic β-cells and/or peripheral insulin resistance, resulting in impaired glucose and lipid metabolism. Genetic, metabolic, multiple lifestyle, and sociodemographic factors are known as related to high T2DM risk. Dietary lipids and lipid metabolism are significant metabolic modulators in T2DM and T2DM-related complications. Besides, accumulated evidence suggests that altered gut microbiota which plays an important role in the metabolic health of the host contributes significantly to T2DM involving impaired or improved glucose and lipid metabolism. At this point, dietary lipids may affect host physiology and health via interaction with the gut microbiota. Besides, increasing evidence in the literature suggests that lipidomics as novel parameters detected with holistic analytical techniques have important roles in the pathogenesis and progression of T2DM, through various mechanisms of action including gut-brain axis modulation. A better understanding of the roles of some nutrients and lipidomics in T2DM through gut microbiota interactions will help develop new strategies for the prevention and treatment of T2DM. However, this issue has not yet been entirely discussed in the literature. The present review provides up-to-date knowledge on the roles of dietary lipids and lipidomics in gut-brain axis in T2DM and some nutritional strategies in T2DM considering lipids- lipidomics and gut microbiota interactions are given. [ABSTRACT FROM AUTHOR]

Background: Yarrowia lipolytica is a well-studied oleaginous yeast known for its ability to accumulate and store intracellular lipids, while growing on diverse, non-conventional substrates. Amongst them, crude glycerol, a low-cost by-product of the biodiesel industry, appears to be an interesting option for scaling up a sustainable single-cell oil production process. Adaptive laboratory evolution (ALE) is a powerful tool to force metabolic adaptations endowing tolerance to stressful environmental conditions, generating superior phenotypes with industrial relevance. Results: Y. lipolytica MUCL 28849 underwent ALE in a synthetic medium with increasing concentration of pure or crude glycerol as a stressing factor (9–20% v/v) for 520 generations. In one case of pure glycerol, chemical mutagenesis with ethyl methanesulfonate (EMS) was applied prior to ALE. Growth profile, biomass production and lipid content of 660 evolved strains (EVS), revealed 5 superior isolates; exhibiting from 1.9 to 3.6-fold increase of dry biomass and from 1.1 to 1.6-fold increase of lipid concentration compared to the parental strain, when grown in 15% v/v crude glycerol. NGS for differential gene expression analysis, showed induced expression in all EVS affecting nucleosomal structure and regulation of transcription. As strains differentiated, further changes accumulated in membrane transport and protein transport processes. Genes involved in glycerol catabolism and triacylglycerol biosynthesis were overexpressed in two EVS. Mismatches and gaps in the expressed sequences identified altered splicing and mutations in the EVS, with most of them, affecting different components of septin ring formation in the budding process. The selected YLE155 EVS, used for scale-up cultivation in a 3L benchtop bioreactor with 20% v/v crude glycerol, achieved extended exponential phase, twofold increase of dry biomass and lipid yields at 48 h, while citric acid secretion and glycerol consumption rates were 40% and 50% lower, respectively, compared to the parental strain, after 24 h of cultivation. Conclusion: ALE and EMS-ALE under increasing concentrations of pure or crude glycerol generated novel Y. lipolytica strains with enhanced biomass and lipid content. Differential gene expression analysis and scale-up of YLE155, illustrated the potential of the evolved strains to serve as suitable "chassis" for rational engineering approaches towards both increased lipid accumulation, and production of high-added value compounds, through efficient utilization of crude glycerol. [ABSTRACT FROM AUTHOR]

The tumormicroenvironment (TME) plays a key role in tumor progression. Tumor-associated macrophages (TAMs), which are natural immune cells abundantin the TME, are mainly divided into the anti-tumor M1 subtype and pro-tumor M2 subtype. Due to the high plasticity of TAMs, the conversion of the M1 to M2 phenotype in hypoxic and hypoglycemic TME promotes cancer progression, which is closely related to lipid metabolism. Key factors of lipid metabolism in TAMs, including peroxisome proliferator-activated receptor and lipoxygenase, promote the formation of a tumor immunosuppressive microenvironment and facilitate immune escape. In addition, tumor cells promote lipid accumulation in TAMs, causing TAMs to polarize to the M2 phenotype. Moreover, other factors of lipid metabolism, such as abhydrolase domain containing 5 and fatty acid binding protein, have both promoting and inhibiting effects on tumor cells. Therefore, further research on lipid metabolism in tumors is still required. In addition, statins, as core drugs regulating cholesterol metabolism, can inhibit lipid rafts and adhesion of tumor cells, which can sensitize them to chemotherapeutic drugs. Clinical studies on simvastatin and lovastatin in a variety of tumors are underway. This article provides a comprehensive review of the role of lipid metabolism in TAMs in tumor progression, and provides new ideas for targeting lipid metabolism in tumor therapy. [ABSTRACT FROM AUTHOR]

Objective: We explored the dietary effects of replacing normal dietary staple foods with supplementary nutritional protein powder, dietary fiber, and fish oil on several metabolic parameters. We examined weight loss, glucose and lipid metabolism, and intestinal flora in obese individuals when compared with individuals on a reduced staple food low carbohydrate diet. Methods: From inclusion and exclusion criteria, 99 participants (28 kg/m2 ≤ body mass index (BMI) ≤ 35 kg/m2) were recruited and randomly assigned to control and intervention 1 and 2 groups. Physical examinations and biochemical indices were performed/gathered before the intervention and at 4 and 13 weeks post intervention. After 13 weeks, feces was collected and 16s rDNA sequenced. Results: After 13 weeks, when compared with controls, body weight, BMI, waist circumference, hip circumference, systolic blood pressure, and diastolic blood pressure values in intervention group 1 were significantly reduced. In intervention group 2, body weight, BMI, waist circumference, and hip circumference were significantly reduced. Triglyceride (TG) levels in both intervention groups were significantly reduced. Fasting blood glucose, glycosylated hemoglobin, glycosylated albumin, total cholesterol, and apolipoprotein B levels in intervention group 1 were decreased, while high density lipoprotein cholesterol (HDL-c) decreased slightly. Glycosylated albumin, TG, and total cholesterol levels in intervention group 2 decreased, while HDL-c decreased slightly, High sensitive C-reactive protein, MPO, Ox-LDL, LEP, TGF-β1, IL-6, GPLD1, pro NT, GPC-4, and LPS levels in both intervention groups were lower when compared with controls. Adiponectin (ADPN) levels in intervention groups were higher when compared with controls. Tumor necrosis factor-α (TNF-α) levels in intervention group 1 were lower when compared with controls. There is no obvious difference in α diversity and β diversity between intestinal flora of 3 groups. Among the first 10 species of Phylum, only the control group and the intervention group 2 had significantly higher Patescibacteria than the intervention group 1. Among the first 10 species of Genus, only the number of Agathobacter in intervention group 2 was significantly higher than that in control group and intervention group 1. Conclusions: We showed that an LCD, where nutritional protein powder replaced some staple foods and dietary fiber and fish oil were simultaneously supplemented, significantly reduced weight and improved carbohydrate and lipid metabolism in obese individuals when compared with an LCD which reduced staple food intake. [ABSTRACT FROM AUTHOR]

Background: Choline is an important metabolite involved in phospholipids synthesis, including serum lipids, and is the immediate precursor of betaine. There are numerous studies with inconsistent results that evaluated the association between dietary choline intakes with cardiovascular risk factors. In addition, the association between dietary betaine and choline intakes with cardio-metabolic risk factors is not well studied. In the current study, our aim was to evaluate dietary choline and betaine intakes in the usual diet of obese individuals and to assess its association with serum lipids, blood pressure and glycemic markers among obese individuals. Methods: We recruited a total number of 359 obese people aged between 20 and 50 years in the present study. A semi-quantitative food frequency questionnaire (FFQ) was used for dietary assessment; dietary choline and betaine intakes were calculated using the United States Department of Agriculture (USDA) database. National cholesterol education program adult treatment panel (NCEP-ATP)-III criteria was used metabolic syndrome (MetS) definition. Enzymatic methods were used to assess biochemical variables. Body composition was measured with the bioelectrical impedance analysis (BIA) method. Results: Higher body mass index (BMI), waist to hip ratio (WHR), fat-free mass (FFM) and basal metabolic rate (BMR) were observed in higher tertiles of dietary choline intake (P < 0.01). There was no significant difference in terms of biochemical parameters among different tertiles of dietary choline intake, while systolic blood pressure (SBP) and diastolic blood pressure (DBP) were reduced in higher betaine tertiles (P < 0.05). For total dietary choline and betaine intakes, there was a reduction in DBP and low density lipoprotein (LDL) concentrations (P < 0.05). Also, a non-significant reduction in serum total cholesterol (TC), triglyceride (TG) and MetS prevalence was observed in higher tertiles of dietary choline and betaine intakes. After classification of the study population according to MetS status, there was no significant difference in biochemical variables in subjects with MetS (P > 0.05), while in the non-MetS group, SBP, DBP, TG and insulin levels reduced in higher tertiles of dietary betaine and choline (P > 0.05). Conclusion: According to our findings, higher dietary intakes of choline and betaine were associated with lower levels of blood pressure and LDL concentrations among obese individuals. Further studies are warranted to confirm the results of the current study. [ABSTRACT FROM AUTHOR]

Background: The effect of resistance training (RT) in cardiac rehabilitation (CR) on insulin resistance remains elusive. We examined whether the addition of high-load (HL) or low loads (LL) RT has any effect on the levels of insulin resistance and lipids versus aerobic training (AT) alone in patients with coronary artery disease (CAD). Methods: Seventy-nine CAD patients were randomised to HL-RT [70–80% of one repetition maximum (1-RM)] and AT, LL-RT (35–40% of 1-RM) and AT or AT (50–80% of maximal power output), and 59 patients [75% males, 15% diabetics, age: 61 (8) years, left ventricular ejection fraction: 53 (9) %] completed the study. Plasma levels of glucose, insulin, blood lipids [total cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol and low-density lipoprotein (LDL)] cholesterol and body composition were measured at baseline and post-training (36 training sessions). Results: Training intervention had only time effect on lean mass (p = 0.002), total and LDL cholesterol levels (both p < 0.001), and no effects on levels of glucose and insulin resistance (homeostatic assessment 2-insulin resistance). Total and LDL cholesterols levels decreased following AT [mean difference (95% confidence interval); total cholesterol: − 0.4 mmol/l (− 0.7 mmol/l, − 0.1 mmol/l), p = 0.013; LDL: − 0.4 mmol/l (− 0.7 mmol/l, − 0.1 mmol/l), p = 0.006] and HL-RT [total cholesterol: − 0.5 mmol/l (− 0.8 mmol/l, − 0.2 mmol/l), p = 0.002; LDL: − 0.5 mol/l (− 0.7 mmol/l, − 0.2 mmol/l), p = 0.002]. No associations were observed between post-training change in body composition and post-training change in blood biomarkers. Conclusions: RT when combined with AT had no additional effect beyond AT alone on fasting glucose metabolism, blood lipids and body composition in patients with CAD. Trial registration number NCT04638764. [ABSTRACT FROM AUTHOR]

Background: Metabolomic changes during pregnancy have been suggested to underlie the etiology of gestational diabetes mellitus (GDM). However, research on metabolites during preconception is lacking. Therefore, this study aimed to investigate distinctive metabolites during the preconception phase between GDM and non-GDM controls in a nested case–control study in Singapore. Methods: Within a Singapore preconception cohort, we included 33 Chinese pregnant women diagnosed with GDM according to the IADPSG criteria between 24 and 28 weeks of gestation. We then matched them with 33 non-GDM Chinese women by age and pre-pregnancy body mass index (ppBMI) within the same cohort. We performed a non-targeted metabolomics approach using fasting serum samples collected within 12 months prior to conception. We used generalized linear mixed model to identify metabolites associated with GDM at preconception after adjusting for maternal age and ppBMI. After annotation and multiple testing, we explored the additional predictive value of novel signatures of preconception metabolites in terms of GDM diagnosis. Results: A total of 57 metabolites were significantly associated with GDM, and eight phosphatidylethanolamines were annotated using HMDB. After multiple testing corrections and sensitivity analysis, phosphatidylethanolamines 36:4 (mean difference β: 0.07; 95% CI: 0.02, 0.11) and 38:6 (β: 0.06; 0.004, 0.11) remained significantly higher in GDM subjects, compared with non-GDM controls. With all preconception signals of phosphatidylethanolamines in addition to traditional risk factors (e.g., maternal age and ppBMI), the predictive value measured by area under the curve (AUC) increased from 0.620 to 0.843. Conclusions: Our data identified distinctive signatures of GDM-associated preconception phosphatidylethanolamines, which is of potential value to understand the etiology of GDM as early as in the preconception phase. Future studies with larger sample sizes among alternative populations are warranted to validate the associations of these signatures of metabolites and their predictive value in GDM. [ABSTRACT FROM AUTHOR]