Search

Lipids are organic nonpolar molecules with essential biological and economic importance. While the genetic pathways and regulatory networks of lipid biosynthesis and metabolism have been extensively studied and thoroughly reviewed in oil crops such as soybeans, less attention has been paid to the biological roles of lipids in rice, a staple food for the global population and a model species for plant molecular biology research, leaving a considerable knowledge gap in the biological roles of lipids. In this review, we endeavor to furnish a current overview of the advancements in understanding the genetic foundations and physiological functions of lipids, including triacylglycerol, fatty acids, and very-long-chain fatty acids. We aim to summarize the key genes in lipid biosynthesis, metabolism, and transcriptional regulation underpinning rice's developmental and growth processes, biotic stress responses, abiotic stress responses, fertility, seed longevity, and recent efforts in rice oil genetic improvement.

Aggregation of α-synuclein (αSyn) and its accumulation as Lewy bodies play a central role in the pathogenesis of Parkinson's disease (PD). However, the mechanism by which αSyn aggregates in the brain remains unclear. Biochemical studies have demonstrated that αSyn interacts with lipids, and these interactions affect the aggregation process of αSyn. Furthermore, genetic studies have identified mutations in lipid metabolism-associated genes such as glucocerebrosidase 1 (GBA1) and synaptojanin 1 (SYNJ1) in sporadic and familial forms of PD, respectively. In this review, we focus on the role of lipids in triggering αSyn aggregation in the pathogenesis of PD and propose the possibility of modulating the interaction of lipids with αSyn as a potential therapy for PD.

An over-active renin-angiotensin system (RAS) is characterized by elevated angiotensin II (Ang II). While Ang II can promote metabolic and mitochondrial dysfunction in tissues, little is known about its role in the gastrointestinal system (GI). Here, we treated rat primary colonic epithelial cells with Ang II (1-5000 nM) to better define their role in the GI. We hypothesized that Ang II would negatively affect mitochondrial bioenergetics as these organelles express Ang II receptors. Ang II increased cellular ATP production but reduced the mitochondrial membrane potential (MMP) of colonocytes. However, cells maintained mitochondrial oxidative phosphorylation and glycolysis with treatment, reflecting metabolic compensation with impaired MMP. To determine whether lipid dysregulation was evident, untargeted lipidomics were conducted. A total of 1949 lipids were detected in colonocytes spanning 55 distinct (sub)classes. Ang II (1 nM) altered the abundance of some sphingosines [So(d16:1)], ceramides [Cer-AP(t18:0/24:0)], and phosphatidylcholines [OxPC(16:0_20:5(2O)], while 100 nM Ang II altered some triglycerides and phosphatidylserines [PS(19:0_22:1). Ang II did not alter the relative expression of several enzymes in lipid metabolism; however, the expression of pyruvate dehydrogenase kinase 2 ( PDK2 ) was increased, and PDK2 can be protective against dyslipidemia. This study is the first to investigate the role of Ang II in colonic epithelial cell metabolism.

In addition to direct damage to hepatocytes, long-term ethanol consumption leads to lipid accumulation and hepatic steatosis, as well as to the dysregulation of lipid metabolism. The final step in various liver diseases is cirrhosis. The aim of this study was to compare the FA (fatty acids) profile and expression levels of genes involved in lipid metabolism in cirrhotic liver tissue and normal liver tissue. Exploring the changes in the FA profile and expression of genes related to fatty acid metabolism in cirrhotic liver tissue reveals a molecular landscape that goes beyond the surface of traditional liver function assessments. Understanding the shifts in gene expression and fatty acid composition in liver tissue opens avenues for interventions that may aid in the treatment of cirrhosis in the future.

Extreme inflammation that continues even after infections can lead to a cytokine storm. In recent times, one of the most common causes of cytokine storm activation has been SARS-CoV-2 infection. A cytokine storm leads to dysregulation and excessive stimulation of the immune system, producing symptoms typical of post-COVID syndrome, including chronic fatigue, shortness of breath, joint pain, trouble concentrating (known as "brain fog"), and even direct organ damage in the heart, lungs, kidneys, and brain. This work summarizes the current knowledge regarding inflammation and the cytokine storm related to SARS-CoV-2 infection. Additionally, changes in lipid metabolism and microbiota composition under the influence of inflammation in COVID-19, along with the possible underlying mechanisms, are described. Finally, this text explores potential health implications related to changes in eating behaviors and nutritional status in COVID-19 patients. Although research on the cytokine storm is still ongoing, there is convincing evidence suggesting that severe immune and inflammatory responses during the acute phase of COVID-19 may lead to long-term health consequences. Understanding these links is key to developing treatment strategies and supporting patients after infection.

Maternal metabolism during pregnancy shapes offspring health via in utero programming. In the Healthy Start study, we identified five subgroups of pregnant women based on conventional metabolic biomarkers: Reference ( n = 360); High HDL-C ( n = 289); Dyslipidemic-High TG ( n = 149); Dyslipidemic-High FFA ( n = 180); Insulin Resistant (IR)-Hyperglycemic ( n = 87). These subgroups not only captured metabolic heterogeneity among pregnant participants but were also associated with offspring obesity in early childhood, even among women without obesity or diabetes. Here, we utilize metabolomics data to enrich characterization of the metabolic subgroups and identify key compounds driving between-group differences. We analyzed fasting blood samples from 1065 pregnant women at 18 gestational weeks using untargeted metabolomics. We used weighted gene correlation network analysis (WGCNA) to derive a global network based on the Reference subgroup and characterized distinct metabolite modules representative of the different metabolomic profiles. We used the mummichog algorithm for pathway enrichment and identified key compounds that differed across the subgroups. Eight metabolite modules representing pathways such as the carnitine-acylcarnitine translocase system, fatty acid biosynthesis and activation, and glycerophospholipid metabolism were identified. A module that included 189 compounds related to DHA peroxidation, oxidative stress, and sex hormone biosynthesis was elevated in the Insulin Resistant-Hyperglycemic vs. the Reference subgroup. This module was positively correlated with total cholesterol (R:0.10; p -value < 0.0001) and free fatty acids (R:0.07; p -value < 0.05). Oxidative stress and inflammatory pathways may underlie insulin resistance during pregnancy, even below clinical diabetes thresholds. These findings highlight potential therapeutic targets and strategies for pregnancy risk stratification and reveal mechanisms underlying the developmental origins of metabolic disease risk.

Plant lipids are essential cell constituents with many structural, storage, signaling, and defensive functions. During plant-pathogen interactions, lipids play parts in both the preexisting passive defense mechanisms and the pathogen-induced immune responses at the local and systemic levels. They interact with various components of the plant immune network and can modulate plant defense both positively and negatively. Under biotic stress, lipid signaling is mostly associated with oxygenated natural products derived from unsaturated fatty acids, known as oxylipins; among these, jasmonic acid has been of great interest as a specific mediator of plant defense against necrotrophic pathogens. Although numerous studies have documented the contribution of oxylipins and other lipid-derived species in plant immunity, their specific roles in plant-pathogen interactions and their involvement in the signaling network require further elucidation. This review presents the most relevant and recent studies on lipids and lipid-derived signaling molecules involved in plant-pathogen interactions, with the aim of providing a deeper insight into the mechanisms underpinning lipid-mediated regulation of the plant immune system.

Malonyl-CoA decarboxylase ( MCD ) is a major regulator of fatty acid oxidation catalyzing the decarboxylation of malonyl coenzyme A (malonyl-CoA). Although its involvement in human diseases has been well studied, its role in intramuscular fat (IMF) deposition remains unknown. In this present study, 1726 bp of MCD cDNA was cloned (OM937122) from goat liver, including 5'UTR of 27 bp, 3'UTR of 199 bp, and CDS of 1500 bp, encoding 499 amino acids. In this present study, although the overexpression of MCD increased the mRNA expression of FASN and DGAT2 , the expression of ATGL and ACOX1 was also activated significantly and resulted in a decrease in cellular lipid deposition in goat intramuscular preadipocytes. Meanwhile, the silencing of MCD increased the cellular lipid deposition and was accompanied by the expression activation of DGAT2 and the expression suppression of ATGL and HSL , despite the expression suppression of genes related to fatty acid synthesis, including ACC and FASN . However, the expression of DGAT1 was not affected significantly ( p > 0.05) by the expression alteration of MCD in this present study. Furthermore, 2025 bp of MCD promoter was obtained and predicted to be regulated by C/EBPα, SP1, SREBP1, and PPARG. In summary, although different pathways may respond to the expression alteration of MCD , the expression of MCD was negatively correlated with the cellular lipid deposition in goat intramuscular preadipocytes. These data may be beneficial for enhancing our understanding of the regulation of IMF deposition in goats., Competing Interests: The authors declare no conflicts of interest.

Cancer is increasingly recognized as an extraordinarily heterogeneous disease featuring an intricate mutational landscape and vast intra- and intertumor variability on both genetic and phenotypic levels. Prostate cancer (PCa) is the second most prevalent malignant disease among men worldwide. A single metabolic program cannot epitomize the perplexing reprogramming of tumor metabolism needed to sustain the stemness of neoplastic cells and their prominent energy-consuming functional properties, such as intensive proliferation, uncontrolled growth, migration, and invasion. In cancerous tissue, lipids provide the structural integrity of biological membranes, supply energy, influence the regulation of redox homeostasis, contribute to plasticity, angiogenesis and microenvironment reshaping, mediate the modulation of the inflammatory response, and operate as signaling messengers, i.e., lipid mediators affecting myriad processes relevant for the development of the neoplasia. Comprehensive elucidation of the lipid metabolism alterations in PCa, the underlying regulatory mechanisms, and their implications in tumorigenesis and the progression of the disease are gaining growing research interest in the contemporary urologic oncology. Delineation of the unique metabolic signature of the PCa featuring major aberrant pathways including de novo lipogenesis, lipid uptake, storage and compositional reprogramming may provide novel, exciting, and promising avenues for improving diagnosis, risk stratification, and clinical management of such a complex and heterogeneous pathology.

The intestinal microbiota contributes to energy metabolism, but the molecular mechanisms involved remain less clear. Bacteria of the genus Bacillus regulate lipid metabolism in the host and are thus commonly used as beneficial probiotic supplements. In the present study, Bacillus licheniformis FA6 was selected to assess its role in modulating lipid metabolism of zebrafish ( Danio rerio ). Combining 16S rRNA high-throughput sequencing, micro-CT scan, metabolic parameters measurement, and gene expression analysis, we demonstrated that B. licheniformis FA6 changed the gut microbiota composition of zebrafish and increased both the Firmicutes/Bacteroidetes ratio and lipid accumulation. In terms of metabolites, B. licheniformis FA6 appeared to promote acetate production, which increased acetyl-CoA levels and promoted lipid synthesis in the liver. In contrast, addition of B. licheniformis lowered carnitine levels, which in turn reduced fatty acid oxidation in the liver. At a molecular level, B. licheniformis FA6 upregulated key genes regulating de novo fatty acid synthesis and downregulated genes encoding key rate-limiting enzymes of fatty acid β-oxidation, thereby promoting lipid synthesis and reducing fatty acid oxidation. Generally, our results reveal that B. licheniformis FA6 promotes lipid accumulation in zebrafish through improving lipid synthesis and reducing β-oxidation.

Objective: This study examined the association between serum ferritin and dyslipidemia in children and adolescents with different degrees of obesity., Method: In this multi-stage, stratified, randomized, sampling cross-section cohort study, demographic data were collected by questionnaire from 4320 children and adolescents (aged 6-17 years) in Shanghai, China. Anthropometric measures and percent body fat (PBF) were recorded. Serum lipid parameters were detected by an automatic biochemical method, and ferritin levels were measured by an automatic immunoassay., Results: Our results showed 70.6%, 13.9%, and 15.5% of participants had a healthy body fat, low fat, and overweight/obese, respectively. Increasing ferritin quartiles were independently associated with a greater hazard of dyslipidemia, especially in overweight/obese participants, and the OR (95% CI) was 3.01 (1.29-7.00), 3.58 (1.59-8.04), and 5.66 (2.57-12.46) across the ferritin quartiles after adjustment for confounders. Ferritin was only a predictive value for dyslipidemia in overweight/obese participants (AUC = 0.64) and was consistent in boys (AUC = 0.61) and girls (AUC = 0.68). The significant positive correlation between ferritin value and lipid abnormalities profiles (except for low HDL-C) mainly appeared in the overweight/obesity group., Conclusion: The results showed that serum ferritin can be considered an independent risk factor for dyslipidemia in children and adolescents with obesity., Highlights: Ferritin overload had a greater risk of dyslipidemia, especially in children and adolescents with overweight/obesity.

There is a wide variety of kinds of lipids, and complex structures which determine the diversity and complexity of their functions. With the basic characteristic of water insolubility, lipid molecules are independent of the genetic information composed by genes to proteins, which determine the particularity of lipids in the human body, with water as the basic environment and genes to proteins as the genetic system. In this review, we have summarized the current landscape on hormone regulation of lipid metabolism. After the well-studied PI3K-AKT pathway, insulin affects fat synthesis by controlling the activity and production of various transcription factors. New mechanisms of thyroid hormone regulation are discussed, receptor α and β may mediate different procedures, the effect of thyroid hormone on mitochondria provides a new insight for hormones regulating lipid metabolism. Physiological concentration of adrenaline induces the expression of extrapituitary prolactin in adipose tissue macrophages, which promotes fat weight loss. Manipulation of hormonal action has the potential to offer a new therapeutic horizon for the global burden of obesity and its associated complications such as morbidity and mortality.

Deep efforts have been devoted to studying the fundamental mechanisms ruling genome integrity preservation. A strong focus relies on our comprehension of nucleic acid and protein interactions. Comparatively, our exploration of whether lipids contribute to genome homeostasis and, if they do, how, is severely underdeveloped. This disequilibrium may be understood in historical terms, but also relates to the difficulty of applying classical lipid-related techniques to a territory such as a nucleus. The limited research in this domain translates into scarce and rarely gathered information, which with time further discourages new initiatives. In this review, the ways lipids have been demonstrated to, or very likely do, impact nuclear transactions, in general, and genome homeostasis, in particular, are explored. Moreover, a succinct yet exhaustive battery of available techniques is proposed to tackle the study of this topic while keeping in mind the feasibility and habits of "nucleus-centered" researchers.

Breastfeeding is a unique and defining behavior of mammals and has a fundamental role in nourishing offspring by supplying a lipid-rich product that is utilized to generate heat and metabolic fuel. Heat generation from lipids is a feature of newborn mammals and is mediated by the uncoupling of mitochondrial respiration in specific fat depots. Breastfeeding and thermogenic adipose tissue have a shared evolutionary history: both have evolved in the course of homeothermy evolution; breastfeeding mammals are termed "thermolipials", meaning "animals with warm fat". Beyond its heat-producing capacity, thermogenic adipose tissue is also necessary for proper lipid metabolism and determines adiposity in offspring. Recent advances have demonstrated that lipid metabolism in infants is orchestrated by breast milk lipid signals, which establish mother-to-child signaling and control metabolic development in the infant. Breastfeeding rates are declining worldwide, and are paralleled by an alarming increase in childhood obesity, which at least in part may have its roots in the impaired metabolic control by breast milk lipid signals.

Long-term exposure to microgravity is considered to cause liver lipid accumulation, thereby increasing the risk of non-alcoholic fatty liver disease (NAFLD) among astronauts. However, the reasons for this persistence of symptoms remain insufficiently investigated. In this study, we used tandem mass tag (TMT)-based quantitative proteomics techniques, as well as non-targeted metabolomics techniques based on liquid chromatography–tandem mass spectrometry (LC–MS/MS), to comprehensively analyse the relative expression levels of proteins and the abundance of metabolites associated with lipid accumulation in rat liver tissues under simulated microgravity conditions. The differential analysis revealed 63 proteins and 150 metabolites between the simulated microgravity group and the control group. By integrating differentially expressed proteins and metabolites and performing pathway enrichment analysis, we revealed the dysregulation of major metabolic pathways under simulated microgravity conditions, including the biosynthesis of unsaturated fatty acids, linoleic acid metabolism, steroid hormone biosynthesis and butanoate metabolism, indicating disrupted liver metabolism in rats due to weightlessness. Finally, we examined differentially expressed proteins associated with lipid metabolism in the liver of rats exposed to stimulated microgravity. These findings contribute to identifying the key molecules affected by microgravity and could guide the design of rational nutritional or pharmacological countermeasures for astronauts. [ABSTRACT FROM AUTHOR]

The standard of care for glioblastoma (GBM) involves surgery followed by adjuvant radio- and chemotherapy, but often within months, patients relapse, and this has been linked to glioma stem cells (GSCs), self-renewing cells with increased therapy resistance. The identification of the epidermal growth factor receptor (EGFR) and platelet-derived growth factor receptor (PDGFR) as key players in gliomagenesis inspired the development of inhibitors targeting these tyrosine kinases (TKIs). However, results from clinical trials testing TKIs have been disappointing, and while the role of GSCs in conventional therapy resistance has been extensively studied, less is known about resistance of GSCs to TKIs. In this study, we have used compartmentalised proteomics to analyse the adaptive response of GSCs to ponatinib, a TKI with activity against PDGFR. The analysis of differentially expressed proteins revealed that GSCs respond to ponatinib by broadly rewiring lipid metabolism, involving fatty acid beta-oxidation, cholesterol synthesis, and sphingolipid degradation. Inhibiting each of these metabolic pathways overcame ponatinib adaptation of GSCs, but interrogation of patient data revealed sphingolipid degradation as the most relevant pathway in GBM. Our data highlight that targeting lipid metabolism, and particularly sphingolipid degradation in combinatorial therapies, could improve the outcome of TKI therapies using ponatinib in GBM. [ABSTRACT FROM AUTHOR]

Jingzhi Guanxin Oral Liquids (JZGX), a traditional Chinese medicine formulation prepared from the decoction of five herbs, has been utilized to relieve chest pain with coronary artery disease (CAD). However, the chemical composition and therapeutic mechanisms of JZGX remain obscured. In this research, the potential targets and pathways of JZGX against CAD were anticipated through network pharmacology based on analyzing its chemical constituents using UPLC-Q-TOF-MS/MS. One hundred seven ingredients in JZGX were identified. The 39 active chemicals and 37 key targets were screened, and CAD-related signaling pathways were clustered, mainly associated with lipid metabolism. Subsequently, the atherosclerotic CAD animal model employing 24 weeks of high-fat diet (HFD) ApoE−/− mice was constructed to investigate the JZGX efficacy and underlying mechanisms validating network forecasts. The histological staining examination and cardiovascular biomarker tests confirmed that JZGX reduced plaque formation in the aorta and decreased blood lipids in vivo. It featured anti-inflammatory, anti-thrombotic, and myocardial protective effects. JZGX prevented excessive lipid deposits and inflammation within the liver and exhibited hepatoprotective properties. Serum untargeted metabolomics analysis indicated that JZGX ameliorated metabolic abnormalities in atherosclerotic CAD mice and prompted lipid metabolism, especially linoleic acid. The PPARs and attached critical targets (SREBP1, FASN, PTGS2, and CYP3A), filtered from the networks and connected with lipid metabolism, were dramatically modulated through JZGX administration, as revealed by western blotting. The molecular docking outcomes showed that all 39 active ingredients in JZGX had good binding activity with PPARα and PPARγ. These findings illustrate that JZGX alleviates atherosclerotic CAD progression by remodeling the lipid metabolism and regulating PPAR-related proteins. [ABSTRACT FROM AUTHOR]

For either healthy or diseased organisms, lipids are key components for cellular membranes; they play important roles in numerous cellular processes including cell growth, proliferation, differentiation, energy storage and signaling. Exercise and disease development are examples of cellular environment alterations which produce changes in these networks. There are indications that alterations in lipid metabolism contribute to the development and progression of a variety of cancers. Measuring such alterations and understanding the pathways involved is critical to fully understand cellular metabolism. The demands for this information have led to the emergence of lipidomics, which enables the large-scale study of lipids using mass spectrometry (MS) techniques. Mass spectrometry has been widely used in lipidomics and allows us to analyze detailed lipid profiles of cancers. In this article, we discuss emerging strategies for lipidomics by mass spectrometry; targeted, as opposed to global, lipid analysis provides an exciting new alternative method. Additionally, we provide an introduction to lipidomics, lipid categories and their major biological functions, along with lipidomics studies by mass spectrometry in cancer samples. Further, we summarize the importance of lipid metabolism in oncology and tumor microenvironment, some of the challenges for lipodomics, and the potential for targeted approaches for screening pharmaceutical candidates to improve the therapeutic efficacy of treatment in cancer patients. [ABSTRACT FROM AUTHOR]

Background/Objectives: Lipid metabolism plays an important role in maternal health and fetal development. There is a gap in the knowledge of how lipid metabolism changes during pregnancy for Black women who are at a higher risk of adverse outcomes. We hypothesized that the comprehensive lipidome profiles would show variation across pregnancy indicative of requirements during gestation and fetal development. Methods: Black women were recruited at prenatal clinics. Plasma samples were collected at 8–18 weeks (T1), 22–29 weeks (T2), and 30–36 weeks (T3) of pregnancy. Samples from 64 women who had term births (≥37 weeks gestation) were subjected to "shotgun" Orbitrap mass spectrometry. Mixed-effects models were used to quantify systematic changes and dimensionality reduction models were used to visualize patterns and identify reliable lipid signatures. Results: Total lipids and major lipid classes showed significant increases with the progression of pregnancy. Phospholipids and glycerolipids exhibited a gradual increase from T1 to T2 to T3, while sphingolipids and total sterol lipids displayed a more pronounced increase from T2 to T3. Acylcarnitines, hydroxy acylcarnitines, and Lyso phospholipid levels significantly decreased from T1 to T3. A deviation was that non-esterified fatty acids decreased from T1 to T2 and increased again from T2 to T3, suggestive of a potential role for these lipids during the later stages of pregnancy. The fatty acids showing this trend included key fatty acids—non-esterified Linoleic acid, Arachidonic acid, Alpha-linolenic acid, Eicosapentaenoic acid, Docosapentaenoic acid, and Docosahexaenoic acid. Conclusions: Mapping lipid patterns and identifying lipid signatures would help develop intervention strategies to reduce perinatal health disparities among pregnant Black women. [ABSTRACT FROM AUTHOR]

The metabolism of glucose and lipids plays a crucial role in the normal homeostasis of the body. Although glucose is the main energy substrate, in its absence, lipid metabolism becomes the primary source of energy. The main means of fatty acid oxidation (FAO) takes place in the mitochondrial matrix through β-oxidation. Glioblastoma (GBM) is the most common form of primary malignant brain tumor (45.6%), with an incidence of 3.1 per 100,000. The metabolic changes found in GBM cells and in the surrounding microenvironment are associated with proliferation, migration, and resistance to treatment. Tumor cells show a remodeling of metabolism with the use of glycolysis at the expense of oxidative phosphorylation (OXPHOS), known as the Warburg effect. Specialized fatty acids (FAs) transporters such as FAT, FABP, or FATP from the tumor microenvironment are overexpressed in GBM and contribute to the absorption and storage of an increased amount of lipids that will provide sufficient energy used for tumor growth and invasion. This review provides an overview of the key enzymes, transporters, and main regulatory pathways of FAs and ketone bodies (KBs) in normal versus GBM cells, highlighting the need to develop new therapeutic strategies to improve treatment efficacy in patients with GBM. [ABSTRACT FROM AUTHOR]

Lipid droplet (LD) accumulation in hepatocytes is one of the major symptoms associated with fatty liver disease. Mitochondria play a key role in catabolizing fatty acids for energy production through β-oxidation. The interplay between mitochondria and LD assumes a crucial role in lipid metabolism, while it is obscure how mitochondrial morphology affects systemic lipid metabolism in the liver. We previously reported that cilnidipine, an already existing anti-hypertensive drug, can prevent pathological mitochondrial fission by inhibiting protein–protein interaction between dynamin-related protein 1 (Drp1) and filamin, an actin-binding protein. Here, we found that cilnidipine and its new dihydropyridine (DHP) derivative, 1,4-DHP, which lacks Ca2+ channel-blocking action of cilnidipine, prevent the palmitic acid-induced Drp1–filamin interaction, LD accumulation and cytotoxicity of human hepatic HepG2 cells. Cilnidipine and 1,4-DHP also suppressed the LD accumulation accompanied by reducing mitochondrial contact with LD in obese model and high-fat diet-fed mouse livers. These results propose that targeting the Drp1–filamin interaction become a new strategy for the prevention or treatment of fatty liver disease. [ABSTRACT FROM AUTHOR]

Alzheimer disease (AD) is a heterogeneous and complex disease in which different pathophysiological mechanisms are involved. This heterogenicity can be reflected in different atrophy patterns or clinical manifestations. Regarding biochemical pathways involved in early AD, lipid metabolism plays an important role; therefore, lipid levels have been evaluated as potential AD diagnosis biomarkers, and their levels could be related to different AD clinical manifestations. Therefore, the aim of this work is to study AD lipid profiles from early AD patients and evaluate their clinical significance. For this purpose, untargeted plasma lipidomic analysis was carried out in early AD patients (n = 31) diagnosed with cerebrospinal fluid (CSF) biomarkers. Cluster analysis was carried out to define early AD subgroups according to the lipid levels. Then, the clinical significance of each lipid profile subgroup was studied, analyzing differences for other variables (cognitive status, CSF biomarkers, medication, comorbidities, age, and gender). The cluster analysis revealed two different groups of AD patients. Cluster 1 showed higher levels of plasma lipids and better cognitive status than Cluster 2. However, no differences were found for the other variables (age, gender, medication, comorbidities, cholesterol, and triglycerides levels) between both groups. Plasma lipid levels could differentiate two early AD subgroups, which showed different cognitive statuses. However, further research with a large cohort and longitudinal study evaluating the clinical evolution of these patients is required. In general, it would involve a relevant advance in the knowledge of AD pathological mechanisms, potential treatments, and precision medicine. [ABSTRACT FROM AUTHOR]

Derangement of the epidermal barrier lipids and dysregulated immune responses are key pathogenic features of atopic dermatitis (AD). The Th2-type cytokines interleukin IL-4 and IL-13 play a prominent role in AD by activating the Janus Kinase/Signal Transduction and Activator of Transcription (JAK/STAT) intracellular signaling axis. This study aimed to investigate the role of JAK/STAT in the lipid perturbations induced by Th2 signaling in 3D epidermal equivalents. Tofacitinib, a low-molecular-mass JAK inhibitor, was used to screen for JAK/STAT-mediated deregulation of lipid metabolism. Th2 cytokines decreased the expression of elongases 1, 3, and 4 and serine-palmitoyl-transferase and increased that of sphingolipid delta(4)-desaturase and carbonic anhydrase 2. Th2 cytokines inhibited the synthesis of palmitoleic acid and caused depletion of triglycerides, in association with altered phosphatidylcholine profiles and fatty acid (FA) metabolism. Overall, the ceramide profiles were minimally affected. Except for most sphingolipids and very-long-chain FAs, the effects of Th2 on lipid pathways were reversed by co-treatment with tofacitinib. An increase in the mRNA levels of CPT1A and ACAT1, reduced by tofacitinib, suggests that Th2 cytokines promote FA beta-oxidation. In conclusion, pharmacological inhibition of JAK/STAT activation prevents the lipid disruption caused by the halted homeostasis of FA metabolism. [ABSTRACT FROM AUTHOR]

Detailed investigation of the lipidome remodeling upon normal weight conditions, obesity, or weight loss, as well as the influence of physical activity, can help to understand the mechanisms underlying dyslipidemia in metabolic conditions correlated to the emergence and progression of non-alcoholic fatty liver disease (NAFLD). C57BL/6 male mice were fed a normal diet (ND) or a high-fat diet (HFD) for 20 weeks. Subgroups within the high-fat diet (HFD) group underwent different interventions: some engaged in exercise (HFDex), others were subjected to weight loss (WL) by changing from the HFD to ND, and some underwent a combination of weight loss and exercise (WLex) during the final 8 weeks of the 20-week feeding period. To support our understanding, not only tissue-specific lipid remodeling mechanisms but also the cross-talk between different tissues and their impact on the systemic regulation of lipid metabolism are essential. Exercise and weight loss-induced specific adaptations in the liver and visceral adipose tissue lipidomes of mice were explored by the UPLC–TOF–MS/MS untargeted lipidomics methodology. Lipidomic signatures of ND and HFD-fed mice undergoing weight loss were compared with animals with and without physical exercise. Several lipid classes were identified as contributing factors in the discrimination of the groups by multivariate analysis models, such as glycerolipids, glycerophospholipids, sphingolipids, and fatty acids, with respect to liver samples, whereas triglycerides were the only lipid class identified in visceral adipose tissue. Lipids found to be dysregulated in HFD animals are related to well-established pathways involved in the biosynthesis of PC, PE, and TG metabolism. These show a reversing trend back to basic levels of ND when animals change to a normal diet after 12 weeks, whereas the impact of exercise, though in some cases it slightly enhances the reversing trend, is not clear. [ABSTRACT FROM AUTHOR]

Angiopoietin-like 3 (ANGPTL3) is a hepatokine acting as a negative regulator of lipoprotein lipase (LPL). Vupanorsen, an ANGPTL3 directed antisense oligonucleotide, showed an unexpected increase in liver fat content in humans. Here, we investigated the molecular mechanism linking ANGPTL3 silencing to hepatocyte fat accumulation. Human hepatocarcinoma Huh7 cells were treated with small interfering RNA (siRNA) directed to ANGPTL3, human recombinant ANGPTL3 (recANGPTL3), or their combination. Using Western blot, Oil Red-O, biochemical assays, and ELISA, we analyzed the expression of genes and proteins involved in lipid metabolism. Oil Red-O staining demonstrated that lipid content increased after 48 h of ANGPTL3 silencing (5.89 ± 0.33 fold), incubation with recANGPTL3 (4.08 ± 0.35 fold), or their combination (8.56 ± 0.18 fold), compared to untreated cells. This effect was also confirmed in Huh7-LX2 spheroids. A total of 48 h of ANGPTL3 silencing induced the expression of genes involved in the de novo lipogenesis, such as fatty acid synthase, stearoyl-CoA desaturase, ATP citrate lyase, and Acetyl-Coenzyme A Carboxylase 1 together with the proprotein convertase subtilisin/kexin 9 (PCSK9). Time-course experiments revealed that 6 h post transfection with ANGPTL3-siRNA, the cholesterol esterification by Acyl-coenzyme A cholesterol acyltransferase (ACAT) was reduced, as well as total cholesterol content, while an opposite effect was observed at 48 h. Under the same experimental conditions, no differences in secreted apoB and PCSK9 were observed. Since PCSK9 was altered by the treatment, we tested a possible co-regulation between the two genes. The effect of ANGPTL3-siRNA on the expression of genes involved in the de novo lipogenesis was not counteracted by gene silencing of PCSK9. In conclusion, our in vitro study suggests that ANGPTL3 silencing determines lipid accumulation in Huh7 cells by inducing the de novo lipogenesis independently from PCSK9. [ABSTRACT FROM AUTHOR]

High-fat diets (HFDs) enhance fish growth by optimizing nutrient utilization (i.e., protein-sparing effect); however, their potential negative effects have also encouraged the search for feed additives. This work has investigated the effects of an extract rich in a polyphenolic antioxidant, hydroxytyrosol (HT), supplemented (0.52 g HT/kg feed) in a HFD (24% lipid) in gilthead sea bream (Sparus aurata). Fish received the diet at two ration levels, standard (3% of total fish weight) or restricted (40% reduction) for 8 weeks. Animals fed the supplemented diet at a standard ration had the lowest levels of plasma free fatty acids (4.28 ± 0.23 mg/dL versus 6.42 ± 0.47 in the non-supplemented group) and downregulated hepatic mRNA levels of lipid metabolism markers (ppara, pparb, lpl, fatp1, fabp1, acox1, lipe and lipa), supporting potential fat-lowering properties of this compound in the liver. Moreover, the same animals showed increased muscle lipid content and peroxidation (1.58- and 1.22-fold, respectively, compared to the fish without HT), suggesting the modulation of body adiposity distribution and an enhanced lipid oxidation rate in that tissue. Our findings emphasize the importance of considering this phytocompound as an optimal additive in HFDs for gilthead sea bream to improve overall fish health and condition. [ABSTRACT FROM AUTHOR]

The eradication of the hepatitis C virus (HCV) has revolutionized the hepatology paradigm, halting the progression of advanced liver disease in patients with chronic infection and reducing the risk of hepatocarcinoma. In addition, treatment with direct-acting antivirals can reverse the lipid and carbohydrate abnormalities described in HCV patients. Although HCV eradication may reduce the overall risk of vascular events, it is uncertain whether altered lipid profiles increase the risk of cerebrovascular disease in certain patients. We have conducted a review on HCV and lipid and carbohydrate metabolism, as well as new scientific advances, following the advent of direct-acting antivirals. [ABSTRACT FROM AUTHOR]

This study evaluated effects of high starch (20%) on hematological variations, glucose and lipid metabolism, antioxidant ability, inflammatory responses, and histopathological lesions in largemouth bass. Results showed hepatic crude lipid and triacylglycerol (TAG) contents were notably increased in fish fed high starch. High starch could increase counts of neutrophils, lymphocytes, monocytes, eosinophils, and basophils and serum contents of TAG, TBA, BUN, and LEP (p < 0.05). There were increasing trends in levels of GLUT2, glycolysis, gluconeogenesis, and LDH in fish fed high starch through the AKT/PI3K signal pathway. Meanwhile, high starch not only triggered TAG and cholesterol synthesis, but mediated cholesterol accumulation by reducing ABCG5, ABCG8, and NPC1L1. Significant increases in lipid droplets and vacuolization were also shown in hepatocytes of D3–D7 groups fed high starch. In addition, high starch could decrease levels of mitochondrial Trx2, TrxR2, and Prx3, while increasing ROS contents. Moreover, high starch could notably increase amounts of inflammatory factors (IL-1β, TNF-α, etc.) by activating NLRP3 inflammasome key molecules (GSDME, caspase 1, etc.). In conclusion, high starch could not only induce metabolic disorders via gluconeogenesis and accumulation of glycogen, TAG, and cholesterol, but could disturb redox homeostasis and cause inflammatory responses by activating the NLRP3 inflammasome in largemouth bass. [ABSTRACT FROM AUTHOR]

This study evaluated the positive effects of autumn olive berries (AOBs) extract on delaying aging by improving lipid metabolism in middle-aged Caenorhabditis elegans that had become obese due to a high-glucose (GLU) diet. The total phenolic content and DPPH radical scavenging abilities of freeze-dried AOBs (FAOBs) or spray-dried AOBs (SAOBs) were examined, and FAOBs exhibited better antioxidant activity. HPLC analysis confirmed that catechin is the main phenolic compound of AOBs; its content was 5.95 times higher in FAOBs than in SAOBs. Therefore, FAOBs were used in subsequent in vivo experiments. FAOBs inhibited lipid accumulation in both the young adult and middle-aged groups in a concentration-dependent manner under both normal and 2% GLU conditions. Additionally, FAOBs inhibited ROS accumulation in a concentration-dependent manner under normal and 2% GLU conditions in the middle-aged worms. In particular, FAOB also increased body bending and egg production in middle-aged worms. To confirm the intervention of genetic factors related to lipid metabolism from the effects of FAOB, body lipid accumulation was confirmed using worms deficient in the daf-16, atgl-1, aak-1, and akt-1 genes. Regarding the effect of FAOB on reducing lipid accumulation, the impact was nullified in daf-16-deficient worms under the 2% GLU condition, and nullified in both the daf-16- and atgl-1-deficient worms under fasting conditions. In conclusion, FAOB mediated daf-16 and atgl-1 to regulate lipogenesis and lipolysis in middle-aged worms. Our findings suggest that FAOB improves lipid metabolism in metabolically impaired middle-aged worms, contributing to its age-delaying effect. [ABSTRACT FROM AUTHOR]

The severity of COVID-19 is linked to an imbalanced immune response. The dysregulated metabolism of small molecules and bioactive lipids has also been associated with disease severity. To promote understanding of the disease biochemistry and provide targets for intervention, we applied a range of LC-MS platforms to analyze over 100 plasma samples from patients with varying COVID-19 severity and with detailed clinical information on inflammatory responses (>30 immune markers). This is the third publication in a series, and it reports the results of comprehensive lipidome profiling using targeted LC-MS/MS. We identified 1076 lipid features across 25 subclasses, including glycerophospholipids, sterols, glycerolipids, and sphingolipids, among which 531 lipid features were dramatically changed in the plasma of intensive care unit (ICU) patients compared to patients in the ward. Patients in the ICU showed 1.3–57-fold increases in ceramides, (lyso-)glycerophospholipids, diglycerides, triglycerides, and plasmagen phosphoethanolamines, and 1.3–2-fold lower levels of a cyclic lysophosphatidic acid, sphingosine-1-phosphates, sphingomyelins, arachidonic acid-containing phospholipids, lactosylceramide, and cholesterol esters compared to patients in the ward. Specifically, phosphatidylinositols (PIs) showed strong fatty acid saturation-dependent behavior, with saturated fatty acid (SFA)- and monosaturated fatty acid (MUFA)-derived PI decreasing and polystaturated (PUFA)-derived PI increasing. We also found ~4000 significant Spearman correlations between lipids and multiple clinical markers of immune response with |R| ≥ 0.35 and FDR corrected Q < 0.05. Except for lysophosphatidic acid, lysophospholipids were positively associated with the CD4 fraction of T cells, and the cytokines IL-8 and IL-18. In contrast, sphingosine-1-phosphates were negatively correlated with innate immune markers such as CRP and IL-6. Further indications of metabolic changes in moderate COVID-19 disease were demonstrated in recovering ward patients compared to those at the start of hospitalization, where 99 lipid species were altered (6 increased by 30–62%; 93 decreased by 1.3–2.8-fold). Overall, these findings support and expand on early reports that dysregulated lipid metabolism is involved in COVID-19. [ABSTRACT FROM AUTHOR]

Lipid metabolism participates in various physiological processes and has been shown to be connected to the development and progression of multiple diseases, especially metabolic hepatopathy. Apolipoproteins (Apos) act as vectors that combine with lipids, such as cholesterol and triglycerides (TGs). Despite being involved in lipid transportation and metabolism, the critical role of Apos in the maintenance of lipid metabolism has still not been fully revealed. This study sought to clarify variations related to m6A methylome in ApoF gene knockout mice with disordered lipid metabolism based on the bioinformatics method of transcriptome-wide m6A methylome epitranscriptomics. High-throughput methylated RNA immunoprecipitation sequencing (MeRIP-seq) was conducted in both wild-type (WT) and ApoF knockout (KO) mice. As a result, the liver histopathology presented vacuolization and steatosis, and the serum biochemical assays reported abnormal lipid content in KO mice. The m6A-modified mRNAs were conformed consensus sequenced in eukaryotes, and the distribution was enriched within the coding sequences and 3′ non-coding regions. In KO mice, the functional annotation terms of the differentially expressed genes (DEGs) included cholesterol, steroid and lipid metabolism, and lipid storage. In the differentially m6A-methylated mRNAs, the functional annotation terms included cholesterol, TG, and long-chain fatty acid metabolic processes; lipid transport; and liver development. The overlapping DEGs and differential m6A-modified mRNAs were also enriched in terms of lipid metabolism disorder. In conclusion, transcriptome-wide MeRIP sequencing in ApoF KO mice demonstrated the role of this crucial apolipoprotein in liver health and lipid metabolism. [ABSTRACT FROM AUTHOR]

The impacts of hypolipidemic pharmaceuticals on fish lipid metabolism remain unexplored. However, data points to similar effects and mechanisms of action between fish and humans. Therefore, fish may be a strong model for screening hypolipidemic drug candidates and water pollution by lipid-modulating agents. This study aimed to test a new hypolipidemic model assay with juvenile brown trout using atorvastatin (ATV)—a hypolipidemic chemical. We selected 17α-ethinylestradiol (EE2), known to cause hyperlipidemia in fish, to ensure model functionality. Fish received intramuscular injections of 4 μL/g for two weeks under the following experimental conditions: control—C (0.7% NaCl), solvent control—SC (0.7% NaCl, 0.9% ethanol, 0.1% dimethyl sulfoxide), ATV (0.3 μg/g), EE2 (2 μg/g), and a mixture of both compounds—MIX (0.3 μg/g ATV and 2 μg/g EE2). Endpoints included blood lipid biochemistry, hepatic lipid droplet quantification, and liver mRNA expression of lipid-related target genes (related to lipogenesis, lipid transport, and β-oxidation pathways). ATV lowered blood total cholesterol, high-density lipoproteins (HDL), and low-density lipoproteins (LDL) levels, whilst triglycerides and very-low-density lipoproteins (VLDL) were highest under EE2. Hepatic lipid droplet deposition significantly increased in the ATV, EE2, and MIX groups. ATV and MIX caused a significant downregulation of the peroxisome proliferator-activated receptor γ (pparγ) and acetyl Co-A oxidase 3 (acox3). EE2 upregulated acyl-CoA long-chain synthetase 1 (acsl1) and downregulated both fatty acid binding protein 1 (fabp1) and acetyl Co-A oxidase 1-3I (acox1-3I). ATV caused hypolipidemic effects in juvenile brown trout and could even counteract EE2-stimulated hyperlipidemia, reinforcing the potential of fish hypo- and hyperlipidemic models. [ABSTRACT FROM AUTHOR]

Simple Summary: The effect of Scalarpin 2 (STC2) on chicken hepatic lipid metabolism is still unknown. In this study, we found that genetic variation rs9949205 occurring in the STC2 was significantly associated with chicken body weight at different weeks and carcass traits. The inhibitory effect of STC2 on lipid synthesis in LMH cells was observed, and its expression level in muscle showed a significant association with 176 lipids, predominantly enriched in essential omega-3 and omega-6 fatty acids. The evidence suggests that STC2 involved growth and development, as well as lipid metabolism in chickens. Stanniocalcin 2 (STC2) is a secreted glycoprotein involved in multiple biological processes. To systemically study the biological role of STC2 in chickens, phylogenetic tree analysis and conservation analysis were conducted. Association analysis between variations in the STC2 gene and the economic traits of Gushi-Anka F2 was conducted. The tissue expression patterns of STC2 expression in different chicken tissues and liver at different stages were detected. The biological role of STC2 in chicken liver was investigated through overexpression and interfering methods in the LMH cell line. Correlation analyses between STC2 expression and lipid components were conducted. (1) The phylogenetic tree displayed that chicken STC2 is most closely related with Japanese quail and most distantly related with Xenopus tropicalis. STC2 has the same identical conserved motifs as other species. (2) rs9949205 (T > C) found in STC2 intron was highly significantly correlated with chicken body weight at 0, 2, 4, 6, 8, 10 and 12 weeks (p < 0.01). Extremely significant correlations of rs9949205 with semi-evisceration weight (SEW), evisceration weight (EW), breast muscle weight (BMW), leg muscle weight (LMW), liver weight and abdominal fat weight (AFW) were revealed (p < 0.01). Significant associations between rs9949205 and abdominal fat percentage, liver weight rate, breast muscle weight rate and leg muscle weight rate were also found (p < 0.05). Individuals with TT or TC genotypes had significantly lower abdominal fat percentage and liver weight rate compared to those with the CC genotype, while their body weight and other carcass traits were higher. (3) STC2 showed a high expression level in chicken liver tissue, which significantly increased with the progression of age (p < 0.05). STC2 was observed to inhibit the content of lipid droplets, triglycerides (TG) and cholesterol (TC), as well the expression level of genes related to lipid metabolism in LMH cells. (4) Correlation analysis showed that the STC2 gene was significantly correlated with 176 lipids in the breast muscle (p < 0.05) and mainly enriched in omega-3 and omega-6 unsaturated fatty acids. In conclusion, the STC2 gene in chicken might potentially play a crucial role in chicken growth and development, as well as liver lipid metabolism and muscle lipid deposition. This study provides a scientific foundation for further investigation into the regulatory mechanism of the STC2 gene on lipid metabolism and deposition in chicken liver. [ABSTRACT FROM AUTHOR]

Dysfunctions of lipid metabolism are associated with tumor progression and treatment resistance of cutaneous melanoma. BRAF/MEK inhibitor resistance is linked to alterations of melanoma lipid pathways. We evaluated whether a specific lipid pattern characterizes plasma from melanoma patients and their response to therapy. Plasma samples from patients and controls were analyzed for FASN and DHCR24 levels and lipidomic profiles. FASN and DHCR24 expression resulted in association with disease condition and related to plasma cholesterol and triglycerides in patients at different disease stages (n = 144) as compared to controls (n = 115). Untargeted lipidomics in plasma (n = 40) from advanced disease patients and controls revealed altered levels of different lipids, including fatty acid derivatives and sphingolipids. Targeted lipidomics identified higher levels of dihydroceramides, ceramides, sphingomyelins, ganglioside GM3, sphingosine, sphingosine-1-phosphate, and dihydrosphingosine, saturated and unsaturated fatty acids. When melanoma patients were stratified based on a long/short-term clinical response to kinase inhibitors, differences in plasma levels were shown for saturated fatty acids (FA 16:0, FA18:0) and oleic acid (FA18:1). Our results associated altered levels of selected lipid species in plasma of melanoma patients with a more favorable prognosis. Although obtained in a small cohort, these results pave the way to lipidomic profiling for melanoma patient stratification. [ABSTRACT FROM AUTHOR]

Lipids are a crucial component of the human brain, serving important structural and functional roles. They are involved in cell function, myelination of neuronal projections, neurotransmission, neural plasticity, energy metabolism, and neuroinflammation. Despite their significance, the role of lipids in the development of mental disorders has not been well understood. This review focused on the potential use of lipids as blood biomarkers for common mental illnesses, such as major depressive disorder, anxiety disorders, bipolar disorder, and schizophrenia. This review also discussed the impact of commonly used psychiatric medications, such as neuroleptics and antidepressants, on lipid metabolism. The obtained data suggested that lipid biomarkers could be useful for diagnosing psychiatric diseases, but further research is needed to better understand the associations between blood lipids and mental disorders and to identify specific biomarker combinations for each disease. [ABSTRACT FROM AUTHOR]

Simple Summary: The production of artificially farmed bullfrogs in China is limited by the low metamorphosis rate of tadpoles. This study investigated the effects of different doses (0 g/kg, 1.5 g/kg, 3 g/kg, 4.5 g/kg, and 6 g/kg) of thyroid powder added to the diets on the metamorphosis and growth of bullfrog tadpoles. The results showed that 4.5 g/kg of thyroid powder could significantly increase the metamorphosis rate and weight gain rate of tadpoles, while adding 6 g/kg of thyroid powder could increase the average weight of tadpoles during metamorphosis. In addition, both doses of thyroid powder could promote the fat breakdown metabolism of tadpoles and alter the intestinal microbiota composition (increasing the abundance of beneficial bacteria, especially Akkermansia). In summary, appropriate doses of thyroid powder could promote the metamorphosis and growth of tadpoles, and might be used to solve the problem of the low metamorphosis rate of bullfrogs. A low metamorphosis rate of amphibian larvae, commonly known as tadpoles, limits the farming production of bullfrogs (Lithobates catesbeiana). This study aimed to examine the effects of processed thyroid powder as a feed additive on tadpole metamorphosis, lipid metabolism, and gut microbiota. Five groups of tadpoles were fed with diets containing 0 g/kg (TH0), 1.5 g/kg (TH1.5), 3 g/kg (TH3), 4.5 g/kg (TH4.5), and 6 g/kg (TH6) thyroid powder for 70 days. The results showed that TH increased the average weight of tadpoles during metamorphosis, with the TH6 group having the highest values. The TH4.5 group had the highest metamorphosis rate (p < 0.05). Biochemical tests and Oil Red O staining showed that the lipid (triglyceride) content in the liver decreased after TH supplementation, especially at doses higher than 1.5 g/kg. RT-qPCR revealed that TH at doses higher than 4.5 g/kg significantly up-regulated the transcriptional expression of the pparα, accb, fas, fadd6, acadl, and lcat genes, which are related to lipid metabolism (p < 0.05). These results showed that TH seems to simultaneously promote the synthesis and decomposition of lipid and fatty acids, but ultimately show a decrease in lipids. As for the gut microbiota, it is noteworthy that Verrucomicrobia increased significantly in the TH4.5 and TH6 groups, and the Akkermansia (classified as Verrucomicrobia) was the corresponding genus, which is related to lipid metabolism. Specifically, the metabolic pathways of the gut microbiota were mainly enriched in metabolic-related functions (such as lipid metabolism), and there were significant differences in metabolic and immune pathways between the TH4.5 and TH0 groups (p < 0.05). In summary, TH may enhance lipid metabolism by modulating the gut microbiota (especially Akkermansia), thereby promoting the growth of tadpoles. Consequently, a supplementation of 4.5 g/kg or 6 g/kg of TH is recommended for promoting the metamorphosis and growth of tadpoles. [ABSTRACT FROM AUTHOR]

The effect of nitrogen-modified atmosphere storage (NS) on peanut lipid oxidation was investigated in this paper. Non-targeted lipidomics was employed to detect the lipid metabolites in peanuts with the aim of exploring the mechanism of lipid oxidation in peanuts under different storage conditions. The results showed that compared with conventional storage (CS), NS significantly (p < 0.05) delayed the increase in acid value, carbonyl value, and 2-thiobarbituric acid value and the decrease in vitamin E content. However, the storage time has a much greater effect on lipid oxidation than the oxygen level in the storage environment. Lipidomics analysis revealed that there were significant differences in metabolite changes between CS and NS. NS reduced the decline of most glycerophospholipids by regulating lipid metabolism in peanuts. NS maintained higher levels of Diacylglycerol (DAG), sulfoquinovosyl diacylglycerol (SQDG), lysophophatidylcholine (LPC), lysophosphatidylethanolamine (LPE) and phosphatidylinositol (PI) compared to CS. This work provided a basis for the application of NS technology to peanut storage. [ABSTRACT FROM AUTHOR]

Lipid droplets (LDs) are intracellular organelles that play important roles in cellular lipid metabolism; they change their sizes and numbers in response to both intracellular and extracellular signals. Changes in LD size reflect lipid synthesis and degradation and affect many cellular activities, including energy supply and membrane synthesis. Here, we focused on the function of the endoplasmic reticulum–plasma membrane tethering protein Ice2 in LD dynamics in the fungal pathogen Candida albicans (C. albicans). Nile red staining and size quantification showed that the LD size increased in the ice2Δ/Δ mutant, indicating the critical role of Ice2 in the regulation of LD dynamics. A lipid content analysis further demonstrated that the mutant had lower phosphatidylcholine levels. As revealed with GFP labeling and fluorescence microscopy, the methyltransferase Cho2, which is involved in phosphatidylcholine synthesis, had poorer localization in the plasma membrane in the mutant than in the wild-type strain. Interestingly, the addition of the phosphatidylcholine precursor choline led to the recovery of normal-sized LDs in the mutant. These results indicated that Ice2 regulates LD size by controlling intracellular phosphatidylcholine levels and that endoplasmic reticulum–plasma membrane tethering proteins play a role in lipid metabolism regulation in C. albicans. This study provides significant findings for further investigation of the lipid metabolism in fungi. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) have a significant impact on the pathophysiological processes associated with various diseases such as tumors, inflammation, and infection. They exhibit molecular, biochemical, and entry control characteristics similar to viral infections. Viruses, on the other hand, depend on host metabolic machineries to fulfill their biosynthetic requirements. Due to potential advantages such as biocompatibility, biodegradation, and efficient immune activation, EVs have emerged as potential therapeutic targets against the SARS-CoV-2 infection. Studies on COVID-19 patients have shown that they frequently have dysregulated lipid profiles, which are associated with an increased risk of severe repercussions. Lipid droplets (LDs) serve as organelles with significant roles in lipid metabolism and energy homeostasis as well as having a wide range of functions in infections. The down-modulation of lipids, such as sphingolipid ceramide and eicosanoids, or of the transcriptional factors involved in lipogenesis seem to inhibit the viral multiplication, suggesting their involvement in the virus replication and pathogenesis as well as highlighting their potential as targets for drug development. Hence, this review focuses on the role of modulation of lipid metabolism and EVs in the mechanism of immune system evasion during SARS-CoV-2 infection and explores the therapeutic potential of EVs as well as application for delivering therapeutic substances to mitigate viral infections. [ABSTRACT FROM AUTHOR]

Enteromorpha prolifera (EP) is a green alga that causes green bloom worldwide. This study aimed to isolate and identify n-3 polyunsaturated fatty acids (PUFAs) from EP oil obtained via supercritical fluid extraction (SFE) and to explore its preventive effects against dextran sodium sulfate (DSS)-induced ulcerative colitis in C57BL/6J mice. In EP oil, we found the novel n-3 polyunsaturated fatty acid C16:4n-3 and two unusual fatty acids C18:4n-3 and C16:3n-3, using GC-MS. The administration of EP oil reduced histopathological of symptoms colitis and the shortening of the colon length. Pro-inflammatory cytokines of IL-6 and TNF-α in serum of EP oil treatment were lower than DSS treatment (by 37.63% and 83.52%), and IL-6 gene expression in the colon was lower in than DSS group by 48.28%, and IL-10 in serum was higher than DSS group by 2.88-fold. Furthermore, the protein expression of p-STAT3 by the EP oil treatment was significantly reduced compared with DSS treatment group by 73.61%. Lipidomics study suggested that phosphatidylcholine and phosphatidylethanolamine were positively associated with the anti-inflammatory cytokine IL-10, while cholesteryl ester and sphingomyelin were negatively related to inflammation cytokines in the EP oil group. The present results indicated that EP oil rich in n-3 PUFA contains a novel fatty acid C16:4n-3, as well as two uncommon fatty acids C18:4n-3 and C16:3n-3. EP oil could prevent DSS-induced ulcerative colitis by regulating the JAK/STAT pathway and lipid metabolism. [ABSTRACT FROM AUTHOR]

Our previous study established that chrysoeriol (CHE) can reduce reactive oxygen species (ROS) accumulation, apoptosis, and autophagy in vitro culture (IVC) of porcine embryos. However, the role of CHE in oocyte maturation and lipid homeostasis is unclear. Herein, we aimed to elucidate the effect of CHE on porcine oocyte competence in vitro maturation (IVM) and subsequent embryo development. The study chooses parthenogenetic activated porcine oocytes as the research model. The study revealed that the cumulus expansion index and related gene expressions are significantly elevated after supplementing 1 μM CHE. Although there were no significant differences in nuclear maturation and cleavage rates, the blastocyst formation rate and total cell numbers were significantly increased in the 1 μM CHE group. In addition, CHE improved the expression of genes related to oocyte and embryo development. ROS was significantly downregulated in all CHE treatment groups, and intracellular GSH (glutathione) was significantly upregulated in 0.01, 0.1, and 1 μM CHE groups. The immunofluorescence results indicated that mitochondrial membrane potential (MMP) and lipid droplet (LD), fatty acid (FA), ATP, and functional mitochondria contents significantly increased with 1 μM CHE compared to the control. Furthermore, CHE increased the expression of genes related to lipid metabolism, mitochondrial biogenesis, and β-oxidation. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the antioxidant and antiaging effects of Indian almond (Terminalia catappa Linn.) leaf extract (TCE) on high-glucose (GLU)-induced obese Caenorhabditis elegans. Since TCE contains high contents of flavonoids and phenolics, strong radical scavenging activity was confirmed in vitro. The stress-resistance effect of TCE was confirmed under thermal and oxidative stress conditions at nontoxic tested concentrations (6.25, 12.5, and 25 μg/mL). GLU at 2% caused lipid and reactive oxygen species (ROS) accumulation in C. elegans, and TCE inhibited lipid and ROS accumulation under both normal and 2% GLU conditions in a concentration-dependent manner. In addition, TCE proved to be effective in prolonging the lifespan of C. elegans under normal and 2% GLU conditions. The ROS reduction effect of TCE was abolished in mutants deficient in daf-16/FOXO and skn-1/Nrf-2. In addition, the lifespan-extending effect of TCE in these two mutants disappeared. The lifespan-extending effect was abolished even in atgl-1/ATGL-deficiency mutants. The TCE effect was reduced in aak-1/AMPK-deficient mutants and completely abolished under 2% GLU conditions. Therefore, the effect of prolonging lifespan by inhibiting lipid and ROS accumulation under the high GLU conditions of TCE is considered to be the result of atgl-1, daf-16, and skn-1 being downregulated by aak-1. These results suggest that the physiological potential of TCE contributes to antiaging under metabolic disorders. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2DM) is characterized by high blood glucose levels and lipid alterations. Besides pharmacological treatment, lifestyle modifications and nutraceuticals can be used to manage glucose and lipid profiles, which is crucial for preventing, or avoiding, serious consequences associated with the condition. This randomized controlled clinical trial on 75 patients with T2DM evaluated the effects of a combination of myo-inositol and d-chiro-inositol (40:1), α-lactalbumin, Gymnema sylvestre, and zinc on glucose and lipid profile. The intention-to-treat analysis displayed no significant differences in glucose parameters between the groups; however, the study group displayed reduced levels of total cholesterol (p = 0.01) and LDL (p = 0.03) after 3 months of supplementation. A subgroup analysis involving patients who did not modify their antidiabetic therapy, after 6 months displayed improved levels of total cholesterol (p = 0.03) and LDL (p = 0.04) in the study group versus placebo, along with a greater body weight reduction (p = 0.03) after 3 months. Furthermore, within the study group, levels of HDL (p = 0.03) and triglycerides (p = 0.04) improved after 3 months. These findings support supplementation with myo-inositol and d-chiro-inositol (40:1), α-lactalbumin, Gymnema sylvestre, and zinc as an adjuvant and safe strategy to manage the lipid profiles of patients with T2DM. [ABSTRACT FROM AUTHOR]

Photoperiod is one of the most important environmental cues for organisms, and it plays a crucial role in regulating feeding, behavior, growth, and metabolism. However, seasonal photoperiods are often overlooked in carp culture or experiments, with a poorly understood effect on lipid metabolism and oxidative stress in fish. To explore the effects of seasonal photoperiods, we exposed Huanghe carp (Cyprinus carpio haematopterus) to summer photoperiod (14 h light:10 h dark) and winter photoperiod (10 h light:14 h dark) daylight conditions in an eight-week experiment. Our results suggested that the winter photoperiod significantly increased the liver TG level as well as the transcript levels of genes related to lipid synthesis, indicating that the lipid metabolism in Huanghe carp liver was enhanced compared to summer photoperiod conditions, and that lipid deposition may be responsible for the increase in body weight level and hepatosomatic index. Additionally, MDA, GSH, GSH-PX, and T-AOC levels were significantly elevated in the liver of fish under the winter photoperiod, suggesting that Huanghe carp responded to winter photoperiod exposure-induced oxidative stress in the liver by enhancing the antioxidant response. Based on transcriptome analysis, the winter photoperiod activated hepatic autophagy response and the FOXO signaling pathway in Huanghe carp. Combined with the correlation analysis, the Huanghe carp maintains the physiological health of the liver by activating the FOXO signaling pathway-mediated cell cycle regulation and autophagy response in response to oxidative stress during winter photoperiod exposure. Our study provides the first evidence for the physiological regulation of the liver in Huanghe carp under seasonal photoperiod stimulation. [ABSTRACT FROM AUTHOR]

Lysosomes are degradative organelles that facilitate the removal and recycling of potentially cytotoxic materials and mediate a variety of other cellular processes, such as nutrient sensing, intracellular signaling, and lipid metabolism. Due to these central roles, lysosome dysfunction can lead to deleterious outcomes, including the accumulation of cytotoxic material, inflammation, and cell death. We previously reported that cationic amphiphilic drugs, such as imipramine, alter pH and lipid metabolism within macrophage lysosomes. Therefore, the ability for imipramine to induce changes to the lipid content of isolated macrophage lysosomes was investigated, focusing on sphingomyelin, cholesterol, and glycerophospholipid metabolism as these lipid classes have important roles in inflammation and disease. The lysosomes were isolated from control and imipramine-treated macrophages using density gradient ultracentrifugation, and mass spectrometry was used to measure the changes in their lipid composition. An unsupervised hierarchical cluster analysis revealed a clear differentiation between the imipramine-treated and control lysosomes. There was a significant overall increase in the abundance of specific lipids mostly composed of cholesterol esters, sphingomyelins, and phosphatidylcholines, while lysophosphatidylcholines and ceramides were overall decreased. These results support the conclusion that imipramine's ability to change the lysosomal pH inhibits multiple pH-sensitive enzymes in macrophage lysosomes. [ABSTRACT FROM AUTHOR]

Although the importance of lipid homeostasis in neuronal function is undisputed, how they are regulated within neurons to support their unique function is an area of active study. NHR-49 is a nuclear hormone receptor functionally similar to PPARα, and a major lipid regulator in C. elegans. Although expressed in most tissues, little is known about its roles outside the intestine, the main metabolic organ of C. elegans. Here, using tissue- and neuron-type-specific transgenic strains, we examined the contribution of neuronal NHR-49 to cell-autonomous and non-autonomous nhr-49 mutant phenotypes. We examined lifespan, brood size, early egg-laying, and reduced locomotion on food. We found that lifespan and brood size could be rescued by neuronal NHR-49, and that NHR-49 in cholinergic and serotonergic neurons is sufficient to restore lifespan. For behavioral phenotypes, NHR-49 in serotonergic neurons was sufficient to control egg-laying, whereas no single tissue or neuron type was able to rescue the enhanced on-food slowing behavior. Our study shows that NHR-49 can function in single neuron types to regulate C. elegans physiology and behavior, and provides a platform to further investigate how lipid metabolism in neurons impact neuronal function and overall health of the organism. [ABSTRACT FROM AUTHOR]

Simple Summary: In this study, we investigated the effects of adding soybean oligosaccharides (SBOS) to growing–finishing pig diets on growth performance, carcass traits, meat quality, and fat deposition. SBOS are considered to be one of the causes of diarrhea in piglets. However, their impact on growing and fattening pigs has not been reported. The results of this study showed that adding 0.8% SBOS to the diet of growing–finishing pigs can increase the average daily weight gain. Hindgut fermentation of SBOS, which alters the composition of short-chain fatty acids, was the mechanism behind the reduction in fat deposition in growing–finishing pigs. One hundred and twenty-eight boars and gilts of the Duroc × Landrace × Yorkshire variety with an initial body weight (BW) of 52.49 ± 0.48 kg were used in a randomized complete block design for a 63-day experiment. The four treatment groups were: control diet (CON), CON + 0.2% soybean oligosaccharides (SBOS), CON + 0.4% SBOS, and CON + 0.8% SBOS. The results showed that the average daily weight gain (ADG) was significantly higher in the 0.8% SBOS group than in the CON group on days 0–63 (p < 0.05). Compared with the CON group, adding 0.8% SBOS to the diet significantly increased the carcass weight, dressing percentage, and carcass lean percentage, but decreased the average backfat depth of growing–finishing pigs (p < 0.05). Adding different concentrations (0.2%, 0.4%, and 0.8%) of SBOS to the diet can significantly increase the concentrations of acetate, propionate, and butyrate in feces (p < 0.05). The activities of malic enzyme and fatty acid synthase in the 0.8% group were significantly lower than those in the 0.2% and CON groups (p < 0.05). In summary, 0.8% SBOS supplementation to growing–finishing pigs' diets can reduce lipid deposition and increase ADG. [ABSTRACT FROM AUTHOR]

Obesity induces inflammation in the hypothalamus and adipose tissue, resulting in metabolic disorders. A novel hypothalamic neuropeptide, neurosecretory protein GM (NPGM), was previously identified in the hypothalamus of vertebrates. While NPGM plays an important role in lipid metabolism in chicks, its metabolic regulatory effects in mammals remain unclear. In this study, a novel Cre driver line, NPGM-Cre, was generated for cell-specific manipulation. Cre-dependent overexpression of Npgm led to fat accumulation without increased food consumption in male NPGM-Cre mice. Chemogenetic activation of NPGM neurons in the hypothalamus acutely promoted feeding behavior and chronically resulted in a transient increase in body mass gain. Furthermore, the ablated NPGM neurons exhibited a tendency to be glucose intolerant, with infiltration of proinflammatory macrophages into the adipose tissue. These results suggest that NPGM neurons may regulate lipid storage and inflammatory responses, thereby maintaining glucose homeostasis. [ABSTRACT FROM AUTHOR]

In 2011, the European Food Safety Authority (EFSA) accorded a health claim to olive oil polyphenols in that they protected LDL particles from oxidative damage. However, limited scientific evidence has so far failed to confer any claim of function on the maintenance of normal lipid metabolism. We performed a systematic review and meta-analysis of human RCTs, evaluating the effect of olive oil polyphenol administration on lipid profiles. Previous literature was acquired from six electronic databases until June 2023. A total of 75 articles were retrieved and screened for inclusion criteria, which resulted in the selection of 10 RCTs that evaluated the effect of daily exposure to olive oil polyphenols on serum lipids in adults. Meta-analyses were built by tertiles of outcomes, as follows: low (0–68 mg/kg), medium (68–320 mg/kg), and high (320–600 mg/kg) polyphenols for HDL and LDL cholesterol (HDL-C and LDL-C, respectively), and low (0–59.3 mg/kg), medium (59.3–268 mg/kg), and high (268–600 mg/kg) polyphenols for total cholesterol (TC). The study protocol was registered on PROSPERO (registration code: CRD42023403383). The study design was predominantly cross-over (n = 8 of 10) but also included parallel (n = 2 of 10). The study population was predominantly European and healthy. Daily consumption of olive oil polyphenols did not affect TC levels and only slightly significantly reduced LDL-C, with WMD statistically significant only for high daily consumption of olive oil polyphenols (WMD −4.28, 95%CI −5.78 to −2.77). Instead, our data found a statistically significant HDL-C enhancing effect (WMD pooled effect model: 1.13, 95%CI 0.45; 1.80, heterogeneity 38%, p = 0.04) with WMD by daily exposure level showing a statistically significant improvement effect for low (WMD 0.66, 95%CI 0.10–1.23), medium (WMD 1.36, 95%CI 0.76–1.95), and high (WMD 1.13, 95%CI 0.45–1.80) olive oil polyphenol consumptions. Olive oil polyphenols contribute toward maintaining lipid metabolism. Thus, food labeling regulations should stress this health feature of olive oil, whereby a declaration of the olive oil polyphenol content should be added to products on the market. Consumers need to be aware of the quality and possible health effects of any products they consume, and enforcement of nutrition labels offers the best way of providing this information. [ABSTRACT FROM AUTHOR]

Simple Summary: Palm oil is currently the most widely used fat source for food production, but palm oil production is associated with severe environmental problems. Insect fat from Hermetia illucens larvae might be a suitable alternative fat source, because its production is more sustainable and less harmful to the environment. Thus, the present study investigated the effect of Hermetia fat, as compared to palm oil and soybean oil, on the hepatic lipid metabolism and the plasma metabolome of healthy rats, which were fed diets containing either soybean oil, palm oil, or Hermetia fat for 4 weeks. Growth performance, liver and plasma lipid concentrations, and the expression of hepatic genes involved in lipid metabolism and inflammation did not differ between groups. Plasma metabolomics revealed a clear separation of the plasma metabolomes of the soybean oil group and the other two groups, but not of those of the palm oil and the Hermetia fat group. The present study shows that Hermetia fat exerts no adverse effects on lipid metabolism and inflammatory gene expression in the liver of healthy rats compared to palm oil or soybean oil. Thus, the present findings indicate that Hermetia fat is a safe alternative fat source to palm oil for food production. Palm oil (PO) is currently the most widely used fat source for food production, but insect fat from Hermetia illucens larvae (HF) might be a suitable alternative fat source, because its production is less harmful to the environment. The present study investigated the effect of HF, as compared to PO and soybean oil (SO), on the hepatic lipid metabolism and the plasma metabolome of healthy rats, which were randomly assigned to three groups (n = 10 rats/group), and fed three different semi-synthetic diets containing either SO, PO, or HF as the main fat source for 4 weeks. Feed intake, body weight gain, liver and plasma lipid concentrations, and the hepatic mRNA levels of genes involved in lipid metabolism and inflammation did not differ between groups. Targeted plasma metabolomics revealed 294 out of 630 metabolites analyzed to be different between groups. Principal component analysis showed a clear separation of the plasma metabolomes of the SO group and the other two groups, but no separation of those of the PO and the HF groups. The present study shows that HF exerts no adverse metabolic effects in healthy rats, compared to PO or SO, indicating that HF is a safe alternative fat source to PO for food production. [ABSTRACT FROM AUTHOR]