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The aim of this work was to optimize the process of elaborating liver pâtés and omental lamb fat and to evaluate the quality of the products. Livers and fats were obtained from lambs fed with diets composed of corn and soybean meal that were partially replaced by cupuaçu, tucumã and palm kernel cake. To prepare the pâtés, livers were baked for 20 minutes at 100°C, weighed, seasoned, crushed, packaged and pasteurized. The best formulation of the pâté was with 40% liver, 10% fat, 35% water, and pasteurized for 20 minutes at 65°C. The pâté from the livers of lambs fed with palm kernel cake obtained a higher caloric value of 193.05 kcal/100 g and all pâtés met the recommended microbiological quality. There was a significant effect (p< 0.05) of the diets on the aroma and texture of the liver pâtés of lambs fed corn and soybean meal and palm kernel cake, and these were 6.38 and 3.37, respectively. Thus, the pâtés can be considered an alternative to increase the options for consumption of liver from lambs, and also for adding commercial value to lamb viscera. [ABSTRACT FROM AUTHOR]

Background: Previous observational studies have shown controversial results about the relationship between lipid levels and low back pain (LBP). Herein, we aimed to explore the potential causal relationship between lipid levels and LBP by using the mendelian randomization (MR) analysis. Methods: In this two-sample MR study, data were extracted from publicly available MRC Integrative Epidemiology Unit database. Three single-nucleotide polymorphisms (SNPs) of lipid levels [high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), and triglycerides (TG)] and two SNPs of LBP risk (LBP and back pain) were retrieved and used as genetic instrumental variables. Inverse-variance weighted (IVW), weighted median, MR-Egger, robust adjusted profile score (MR-RAPS), and MR-PRESSO were used to examine the potential causal association between lipid levels and LBP. Results: IVW (fixed effect) estimation indicated that increased HDL-C level was negatively related to the odds of LBP for European populations. [odds ratio (OR) = 0.923, 95% confidence interval (CI): 0.857–0.993, P = 0.0323]. Similar results were also found in IVW (random effect) (OR = 0.923, 95% CI: 0.866–0.983, P = 0.0134), MR-Egger (OR = 0.858, 95%CI: 0.757–0.973, P = 0.0177), MR-RAPS (OR = 0.932, 95%CI: 0.871–0.997, P = 0.0419), and MR-PRESSO (OR = 0.933, 95%CI: 0.880–0.989, P = 0.0198) analyses. Whereas no causal link was observed between LDL-C/TG and LBP risk (P>0.05). Conclusion: This two-sample MR study demonstrated a causal relationship between lipid levels and LBP risk. Further investigations are necessary to elucidate the causal association and specific underlying mechanisms by which lipid levels contribute to the development of LBP. [ABSTRACT FROM AUTHOR]

The motor features of Parkinson's disease result from loss of dopaminergic neurons in the substantia nigra with autophagy dysfunction being closely linked to this disease. While a large body of work focusing on protein effectors of autophagy has been reported, regulation of autophagy by lipids has garnered far less attention. Therefore, we sought to identify endogenous lipid molecules that act as signaling mediators of autophagy in differentiated SH-SY5Y cells, a commonly used dopaminergic neuron-like cell model. In order to accomplish this goal, we assessed the role of a fatty acid-binding protein (FABP) family member on autophagy due to its function as an intracellular lipid chaperone. We focused specifically upon FABP5 due to its heightened expression in dopaminergic neurons within the substantia nigra and SH-SY5Y cells. Here, we report that knockdown of FABP5 resulted in suppression of autophagy in differentiated SH-SY5Y cells suggesting the possibility of an autophagic role for an interacting lipid. A lipidomic screen of FABP5-interacting lipids uncovered hits that include 5-oxo-eicosatetraenoic acid (5OE) and its precursor metabolite, arachidonic acid (AA). Additionally, other long-chain fatty acids were found to bind FABP5, such as stearic acid (SA), hydroxystearic acid (HSA), and palmitic acid (PA). The addition of 5OE, SA, and HSA but not AA or PA, led to potent inhibition of autophagy in SH-SY5Y cells. To identify potential molecular mechanisms for autophagy inhibition by these lipids, RNA-Seq was performed which revealed both shared and divergent signaling pathways between the lipid-treated groups. These findings suggest a role for these lipids in modulating autophagy through diverse signaling pathways and could represent novel therapeutic targets for Parkinson's disease. [ABSTRACT FROM AUTHOR]

The current study aimed to assess the influence of dietary inclusion of cyanobacterium Arthrospira platensis NIOF17/003 as a dry material and as a free-lipid biomass (FL) on the growth performance, body composition, redox status, immune responses, and gene expression of whiteleg shrimp, Litopenaeus vannamei postlarvae. L. vannamei were fed five different supplemented diets; the first group was fed on an un-supplemented diet as a negative control group (C-N), the second group was fed on a commercial diet supplemented with 2% of A. platensis complete biomass as a positive control group (C-P20), whereas, the three remaining groups were fed on a commercial diet supplemented with graded amounts of FL at 1%, 2%, and 3% (FL10, FL20, and FL30, respectively). The obtained results indicated that the diet containing 1% FL significantly increased the growth performance, efficiency of consumed feed, and survival percentage of L. vannamei compared to both C-N and C-P20 groups. As for the carcass analysis, diets containing A. platensis or its FL at higher levels significantly increased the protein, lipid, and ash content compared to the C-N group. Moreover, the shrimp group fed on C-P20 and FL10 gave significantly stimulated higher digestive enzyme activities compared with C-N. The shrimp fed C-P20 or FL exhibited higher innate immune responses and promoted their redox status profile. Also, the shrimp fed a low FL levels significantly upregulated the expression of both the peroxiredoxin (Prx) and prophenoloxidase (PPO1) genes than those receiving C-N. The current results recommended that dietary supplementation with 1% FL is the most effective treatment in promoting the performance and immunity of whiteleg shrimp. [ABSTRACT FROM AUTHOR]

This retrospective study aimed to evaluate the effects on the clinical signs of poisoning and adverse effects of intravenous lipid emulsion treatment in 82 animals (dogs and cats) with suspected poisonings over 18 months. Physical examination parameters and state of consciousness were documented every hour after the intravenous administration of a bolus of 2 ml/kg and 0.25 ml/kg/min over 60 minutes of a 20% intravenous lipid emulsion. The modified Glasgow coma scale and laboratory findings (blood gas analysis, triglyceride, lactate) were evaluated initially and three hours after discontinuing intravenous lipid emulsion administration. A statistical evaluation of the occurrence of adverse effects and the development of laboratory values was performed. A decrease in respiratory rate in the second control (8–12 hours) after ILE was observed. Three hours after completing of the intravenous lipid emulsion, triglyceride concentration increased about 10 times (p <0.001). Venous carbon dioxide partial pressure, bicarbonate, base excess, as well as the electrolytes sodium, potassium and ionized calcium decreased significantly (p <0.001). Patients who experienced a worsening of the modified Glasgow coma scale had a higher increase in triglyceride concentrations (p = 0.041) and plasma lactate (p = 0.034) and a larger decrease in bicarbonate concentrations (p = 0.053) compared to others. About 54% (n = 44) of the patients showed adverse effects which could be attributed to the administration of intravenous lipid emulsion and may be associated with a higher triglyceride increase. All of them were completely reversible within 33 hours. Adverse effects associated with intravenous lipid emulsion therapy were observed in half of the patients and were associated with a higher increase in triglycerides. [ABSTRACT FROM AUTHOR]

Food allergy is widely recognized as a significant health issue, having escalated into a global epidemic, subsequently giving rise to the development of numerous additional complications. Currently, the sole efficient method to curb the progression of allergy is through the implementation of an elimination diet. The increasing number of newly identified allergens makes it harder to completely remove or avoid them effectively. The immunoreactivity of proteins of bacterial origin remains an unexplored topic. Despite the substantial consumption of microbial proteins in our diets, the immunologic mechanisms they might induce require thorough validation. This stands as the primary objective of this study. The primary objective of this study was to evaluate the effects of bacterial proteins on the intestinal barrier and immune system parameters during hypersensitivity induction in both developing and mature organisms. The secondary objective was to evaluate the role of lipids in the immunoreactivity programming of these bacterial proteins. Notably, in this complex, comprehensively designed in vitro, in vivo, and ex vivo trial, the immunoreactivity of various bacterial proteins will be examined. In summary, the proposed study intends to address the knowledge gaps regarding the effects of Lactobacillus microbial proteins on inflammation, apoptosis, autophagy, and intestinal barrier integrity in a single study. [ABSTRACT FROM AUTHOR]

Background: Past studies have demonstrated that patients diagnosed with rheumatoid arthritis (RA) often exhibit abnormal levels of lipids. Furthermore, certain lipid-modifying medications have shown effectiveness in alleviating clinical symptoms associated with RA. However, the current understanding of the causal relationship between lipids, lipid-modifying medications, and the risk of developing RA remains inconclusive. This study employed Mendelian randomization (MR) to investigate the causal connection between lipids, lipid-modifying drugs, and the occurrence of RA. Methods: We obtained genetic variation for lipid traits and drug targets related to lipid modification from three sources: the Global Lipids Genetics Consortium (GLGC), UK Biobank, and Nightingale Health 2020. The genetic data for RA were acquired from two comprehensive meta-analyses and the R8 of FINNGEN, respectively. These variants were employed in drug-target MR analyses to establish a causal relationship between genetically predicted lipid-modifying drug targets and the risk of RA. For suggestive lipid-modified drug targets, we conducted Summary-data-based Mendelian Randomization (SMR) analyses and using expression quantitative trait loci (eQTL) data in relevant tissues. In addition, we performed co-localization analyses to assess genetic confounders. Results: Our analysis revealed no significant causal relationship between lipid and RA. We observed that the genetically predicted 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) -mediated low density lipoprotein cholesterol (LDL-C) (OR 0.704; 95% CI 0.56, 0.89; P = 3.43×10−3), Apolipoprotein C-III (APOC3) -mediated triglyceride (TG) (OR 0.844; 95% CI 0.77, 0.92; P = 1.50×10−4) and low density lipoprotein receptor (LDLR) -mediated LDL-C (OR 0.835; 95% CI 0.73, 0.95; P = 8.81×10−3) were significantly associated with a lowered risk of RA. while Apolipoprotein B-100 (APOB) -mediated LDL-C (OR 1.212; 95%CI 1.05,1.40; P = 9.66×10−3) was significantly associated with an increased risk of RA. Conclusions: Our study did not find any supporting evidence to suggest that lipids are a risk factor for RA. However, we observed significant associations between HMGCR, APOC3, LDLR, and APOB with the risk of RA. [ABSTRACT FROM AUTHOR]

Objective: To investigate the anti-cancer efficacy of ENB101-LNP, an ionizable lipid nanoparticles (LNPs) encapsulating siRNA against E6/E7 of HPV 16, in combination therapy with cisplatin in cervical cancer in vitro and in vivo. Methods: CaSki cells were treated with ENB101-LNP, cisplatin, or combination. Cell viability assessed the cytotoxicity of the treatment. HPV16 E6/E7 gene knockdown was verified with RT-PCR both in vitro and in vivo. HLA class I and PD-L1 were checked by flow cytometry. A xenograft model was made using CaSki cells in BALB/c nude mice. To evaluate anticancer efficacy, mice were grouped. ENB101-LNP was given three times weekly for 3 weeks intravenously, and cisplatin was given once weekly intraperitoneally. Tumor growth was monitored. On day 25, mice were euthanized; tumors were collected, weighed, and imaged. Tumor samples were analyzed through histopathology, immunostaining, and western blot. Results: ENB101-LNP and cisplatin synergistically inhibit CaSki cell growth. The combination reduces HPV 16 E6/E7 mRNA and boosts p21 mRNA, p53, p21, and HLA class I proteins. In mice, the treatment significantly blocked tumor growth and promoted apoptosis. Tumor inhibition rates were 29.7% (1 mpk ENB101-LNP), 29.6% (3 mpk), 34.0% (cisplatin), 47.0% (1 mpk ENB101-LNP-cisplatin), and 68.8% (3 mpk ENB101-LNP-cisplatin). RT-PCR confirmed up to 80% knockdown of HPV16 E6/E7 in the ENB101-LNP groups. Immunohistochemistry revealed increased p53, p21, and HLA-A expression with ENB101-LNP treatments, alone or combined. Conclusion: The combination of ENB101-LNP, which inhibits E6/E7 of HPV 16, with cisplatin, demonstrated significant anticancer activity in the xenograft mouse model of cervical cancer. [ABSTRACT FROM AUTHOR]

Nonalcoholic steatohepatitis (NASH) occurs worldwide and is characterized by lipid accumulation in hepatocytes, hepatic inflammation, fibrosis, and an increased risk of cirrhosis. Although a major proportion of NASH patients exhibit obesity and insulin resistance, 20% lack a high body mass and are categorized as "non-obese NASH". Time-restricted feeding (TRF), limiting daily food intake within certain hours, improves obesity, lipid metabolism, and liver inflammation. Here, we determined whether TRF affects NASH pathology induced by a choline-deficient high-fat diet (CDAHFD), which does not involve obesity. TRF ameliorated the increase in epididymal white adipose tissue and plasma alanine transaminase and aspartate transaminase levels after 8 weeks of a CDAHFD. Although gene expression of TNF alpha in the liver was suppressed by TRF, it did not exhibit a suppressive effect on hepatic lipid accumulation, gene expression of cytokines and macrophage markers (Mcp1, IL1b, F4/80), or fibrosis, as evaluated by Sirius red staining and western blot analysis of alpha-smooth muscle actin. A CDAHFD-induced increase in gene expression related to fibrogenesis (Collagen 1a1 and TGFβ) was neither suppressed by TRF nor that of alpha-smooth muscle actin but was increased by TRF. Our results indicated that TRF has a limited suppressive effect on CDAHFD-induced NASH pathology. [ABSTRACT FROM AUTHOR]

Stable isotope ratios in organisms can be used to estimate dietary source contributions, but lipids must first be accounted for to interpret values meaningfully. Lipids are depleted in heavy isotopes because during lipid synthesis light isotopes of carbon (12C) and hydrogen (1H) are preferentially incorporated. Prior work in larval lampreys has noted unusual lipid effects, which suggest lipids are enriched in the heavy isotope of carbon (13C), but still depleted in the heavy isotope of hydrogen (deuterium; 2H); nitrogen, a relatively rare element in lipids, has not been identified as being as sensitive to lipid content. Our objective was to determine if stable isotope ratios of hydrogen, carbon, and nitrogen behaved as expected in larval lampreys, or if their lipids presented different isotopic behavior. The δ2H, δ13C, and δ15N were measured from the muscle of four lamprey species before and after lipid extraction. In addition, muscle of least brook lamprey (Lampetra aepyptera) was collected every three months for a year from two streams in Maryland. Isotopic ratios were measured in bulk and lipid-extracted muscles, as well as in extracted lipids. The difference between muscle samples before and after lipid extraction (Δδ2H, Δδ13C, Δδ15N) was positively related to lipid proxy (%H or C:N ratio) and were fit best by linear models for Δδ2H and Δδ15N, and by a non-linear model for Δδ13C. The difference between lipid-extracted muscle and lipid δ13C (ΔMLδ13C) was negative and varied between months (ANOVA, F3,53 = 5.05, p < 0.005). Our work suggests that while lipids are often depleted in 13C, this is not a universal rule; however, the depletion of 2H in lipid synthesis appears broadly true. [ABSTRACT FROM AUTHOR]

The biochemical composition of Antarctic krill, Euphausia superba, is largely determined by their feeding behaviour. As they supply energy for animals of a higher trophic level and are also commercialized for human consumption, the interest in research on the species is high. Lipids, especially phospholipids, make up a high proportion of dry weight in krill. Seasonal changes are well documented in the fingerprint of free fatty acids analysed after hydrolysis of phospholipids, but the underlying intact polar lipids are rarely considered. In this study, we evaluated the compositions of intact phospholipids (IPLs) in the stomach, digestive gland and hind gut of Antarctic krill caught in summer and autumn at the Antarctic Peninsula region. Using high-resolution mass spectrometry, the fatty acid composition of 179 intact phospholipids could be resolved. Most IPLs were phosphatidylcholines, followed by phosphatidylethanolamines. Several very long chain polyunsaturated fatty acids up to 38:8, which have not been reported in krill before, were identified. The composition shifted to higher molecular weight IPLs with a higher degree of unsaturation for summer samples, especially for samples of the digestive gland. The data supplied in this paper provides new insights into lipid dynamics between summer and autumn usually described by free fatty acid biomarkers. [ABSTRACT FROM AUTHOR]

Background: Parenteral (intravenous) nutrition is lifesaving for patients with intestinal failure, but long-term use of parenteral nutrition often leads to liver disease. SEFA-6179 is a synthetic medium-chain fatty acid analogue designed to target multiple fatty acid receptors regulating metabolic and inflammatory pathways. We hypothesized that SEFA-6179 would prevent hepatosteatosis and lipotoxicity in a murine model of parenteral nutrition-induced hepatosteatosis. Methods: Two in vivo experiments were conducted. In the first experiment, six-week-old male mice were provided an ad lib fat-free high carbohydrate diet (HCD) for 19 days with orogastric gavage of either fish oil, medium-chain triglycerides, or SEFA-6179 at a low (0.3mmol/kg) or high dose (0.6mmol/kg). In the second experiment, six-week-old mice were provided an ad lib fat-free high carbohydrate diet for 19 days with every other day tail vein injection of saline, soybean oil lipid emulsion, or fish oil lipid emulsion. Mice then received every other day orogastric gavage of medium-chain triglyceride vehicle or SEFA-6179 (0.6mmol/kg). Hepatosteatosis was assessed by a blinded pathologist using an established rodent steatosis score. Hepatic lipid metabolites were assessed using ultra-high-performance liquid chromatography-mass spectrometry. Effects of SEFA-6179 on fatty acid oxidation, lipogenesis, and fatty acid uptake in human liver cells were assessed in vitro. Results: In the first experiment, mice receiving the HCD with either saline or medium-chain triglyceride treatment developed macrovesicular steatosis, while mice receiving fish oil or SEFA-6179 retained normal liver histology. In the second experiment, mice receiving a high carbohydrate diet with intravenous saline or soybean oil lipid emulsion, along with medium chain triglyceride vehicle treatment, developed macrovescular steatosis. Treatment with SEFA-6179 prevented steatosis. In each experiment, SEFA-6179 treatment decreased arachidonic acid metabolites as well as key molecules (diacylglycerol, ceramides) involved in lipotoxicity. SEFA-6179 increased both β- and complete fatty oxidation in human liver cells, while having no impact on lipogenesis or fatty acid uptake. Conclusions: SEFA-6179 treatment prevented hepatosteatosis and decreased toxic lipid metabolites in a murine model of parenteral nutrition-induced hepatosteatosis. An increase in both β- and complete hepatic fatty acid oxidation may underlie the reduction in steatosis. [ABSTRACT FROM AUTHOR]

Long-term high-fat feeding results in intramyocellular lipid accumulation, leading to insulin resistance. Intramyocellular lipid accumulation is related to an energy imbalance between excess fat intake and fatty acid consumption. Alternating current electromagnetic field exposure has been shown to enhance mitochondrial metabolism in the liver and sperm. Therefore, we hypothesized that alternating current electromagnetic field exposure would ameliorate high-fat diet-induced intramyocellular lipid accumulation via activation of fatty acid consumption. C57BL/6J mice were either fed a normal diet (ND), a normal diet and exposed to an alternating current electromagnetic field (ND+EMF), a high-fat diet (HFD), or a high-fat diet and exposed to an alternating current electromagnetic field (HFD+EMF). Electromagnetic field exposure was administered 8 hrs/day for 16 weeks using an alternating current electromagnetic field device (max.180 mT, Hokoen, Utatsu, Japan). Tibialis anterior muscles were collected for measurement of intramyocellular lipids, AMPK phosphorylation, FAT/CD-36, and carnitine palmitoyltransferase (CPT)-1b protein expression levels. Intramyocellular lipid levels were lower in the HFD + EMF than in the HFD group. The levels of AMPK phosphorylation, FAT/CD-36, and CPT-1b protein levels were higher in the HFD + EMF than in the HFD group. These results indicate that alternating current electromagnetic field exposure decreases intramyocellular lipid accumulation via increased fat consumption. [ABSTRACT FROM AUTHOR]

Locating potential mates in non-native habitats is one of the most important challenges faced by invasive vertebrate species. The Argentine black and white tegu lizard (Salvator merianae) is a major invasive reptile species in the contiguous United States and is rapidly expanding its range across Florida and the Southeast, in part due to inadequate management strategies and tools. Because a wide array of reptiles, especially squamates (snakes and lizards), have been well-studied for their reliance on chemical cues to locate conspecifics, our project aimed to isolate chemical cues from tegus and assess the ability of adult males and females to use only these cues to make navigation decisions within a Y-maze. Previously, we found that both males and females can follow conspecific scent trails, but the nature of the specific cues used by the tegus was unknown. In this study, we extracted skin lipids from male and female shed skins acquired during the breeding season then tested the extracts for bioactivity at different dilutions prior to Y-maze trials. Both sexes showed positive reactions (e.g., tongue-flicking, nose taps, scratching) to 2:1 skin lipid:hexane dilutions. In the Y-maze, males (n = 7) and females (n = 7) were run in three types of trailing scenarios with these skin lipid extracts: Male-only (pooled lipid extracts from male shed skins), Female-only (extracts from female shed skins), and Male vs. female. Regardless of the tegu lipid type present, tegus preferred to follow the conspecific lipid trail when paired with a neutral control (peanut oil; 2:1 dilution). They also preferred opposite-sex skin lipid trails when paired with same-sex skin lipid trails. We analyzed our results further by comparing them to those of Richard, Bukovich, et al. (2020). We found a synchronization effect of the skin lipids: sex differences in behavior detectable in the scent trail trials were absent when only conspecific skin lipids were present in the environment. Our results indicate that skin lipids alone are sufficient to facilitate mate tracking in S. merianae, these chemical cues induce reliable behavior, and extracted skin lipids have potential for modifying movement patterns of an invasive reptile in their non-native range. If leveraged in concert with current tegu management strategies (i.e., trapping), extracted skin lipids have the potential to bolster management efficacy but field trials are a requisite next step. [ABSTRACT FROM AUTHOR]

Brown bears (Ursus arctos) prepare for winter by overeating and increasing adipose stores, before hibernating for up to six months without eating, drinking, and with minimal movement. In spring, the bears exit the den without any damage to organs or physiology. Recent clinical research has shown that specific lipids and lipid profiles are of special interest for diseases such as diabetes type 1 and 2. Furthermore, rodent experiments show that lipids such as sulfatide protects rodents against diabetes. As free-ranging bears experience fat accumulation and month-long physical inactivity without developing diabetes, they could possibly be affected by similar protective measures. In this study, we investigated whether lipid profiles of brown bears are related to protection against hibernation-induced damage. We sampled plasma from 10 free-ranging Scandinavian brown bears during winter hibernation and repeated sampling during active state in the summer period. With quantitative shotgun lipidomics and liquid chromatography-mass spectrometry, we profiled 314 lipid species from 26 lipid classes. A principal component analysis revealed that active and hibernation samples could be distinguished from each other based on their lipid profiles. Six lipid classes were significantly altered when comparing plasma from active state and hibernation: Hexosylceramide, phosphatidylglycerol, and lysophosphatidylglycerol were higher during hibernation, while phosphatidylcholine ether, phosphatidylethanolamine ether, and phosphatidylinositol were lower. Additionally, sulfatide species with shorter chain lengths were lower, while longer chain length sulfatides were higher during hibernation. Lipids that are altered in bears are described by others as relevant for and associated with diabetes, which strengthens their position as potential effectors during hibernation. From this analysis, a range of lipids are suggested as potential protectors of bear physiology, and of potential importance in diabetes. [ABSTRACT FROM AUTHOR]

The hydrophilic polymer polyethylene glycol-grafted phospholipid has been used extensively in the study of artificial vesicles, nanomedicine, and antimicrobial peptides/proteins. In this research, the effects of 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N- [methoxy (polyethylene glycol)-2000] (abbreviated PEG-DOPE) on the deformation and poration of giant unilamellar vesicles (GUVs)-induced by anionic magnetite nanoparticles (NPs) have been investigated. For this, the size of the NPs used was 18 nm, and their concentration in the physiological solution was 2.00 μg/mL. GUVs were prepared using the natural swelling method comprising 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and PEG-DOPE. The mole% of PEG-DOPE in the membranes were 0, 2, and 5%. The degree of deformation of the GUVs was quantified by the parameter compactness (Com), which is 1.0 for the spherical-shaped GUVs. The value of Com increases with time during the interactions of NPs with GUVs for any concentration of PEG-DOPE, but the rate of increase is significantly influenced by the PEG-DOPE concentration in the membranes. The average compactness increases with the increase of PEG-DOPE%, and after 60 min of NPs interaction, the values of average compactness for 0, 2, and 5% PEG-DOPE were 1.19 ± 0.02, 1.26 ± 0.03 and 1.35 ± 0.05, respectively. The fraction of deformation (Frd) also increased with the increase of PEG-DOPE%, and at 60 min, the values of Frd for 0 and 5% PEG-DOPE were 0.47 ± 0.02 and 0.63 ± 0.02, respectively. The fraction of poration (Frp) increased with the increase of PEG-DOPE, and at 60 min, the values of Frp for 0 and 5% PEG-DOPE were 0.25 ± 0.02 and 0.48 ± 0.02, respectively. Hence, the presence of PEG-grafted phospholipid in the membranes greatly enhances the anionic magnetite NPs-induced deformation and poration of giant vesicles. [ABSTRACT FROM AUTHOR]

Objective: The association between blood lipid levels and the risk of gastric cancer (GC) is well known. Therefore, to clarify this association, all relevant prospective cohort studies were included in this meta-analysis. Methods: Our study was registered in PROSPERO (CRD42022354899) prior to its commencement. A systematic review and meta-analysis were conducted in accordance with the PRISMA recommendations. Chinese databases (CNKI, CBM, Wanfang, and VIP) and English databases (PubMed, Embase, Web of Science, and the Cochrane Library) were systematically searched up to October 2022. This study included all relevant cohort studies that reported hazard ratios (HRs) or relative risks (RRs) and their corresponding 95% confidence intervals (95% CIs) to examine the association between various lipid profiles (e.g., total cholesterol, triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol) and the risk of developing gastric cancer (GC). Fixed effects or random effects models were used based on the level of heterogeneity among the studies, and these models were employed to obtain pooled hazard ratios. Additionally, sensitivity analysis and publication bias analysis were conducted to ensure the robustness and reliability of the findings. Results: After conducting a systematic search, a total of 10 studies were selected out of 10,525 papers involving a total of 5,564,520 individuals. Among these individuals, there were 41,408 GC cases. The analysis revealed that the highest versus lowest serum total cholesterol (TC) concentration was associated with a pooled hazard ratio of 0.89 (95% CI = 0.87–0.92, I2 = 15%). For triglycerides (TGs), the hazard ratio was 1.00 (95% CI = 0.96–1.04, I2 = 37%), while for high-density lipoprotein cholesterol (HDL-C), the hazard ratio was 0.90 (95% CI = 0.86–0.93, I2 = 0%). The hazard ratio for low-density lipoprotein cholesterol (LDL-C) was 0.96 (95% CI = 0.91–1.00, I2 = 0%). Conclusions: Based on the results of this meta-analysis, it was found that serum TC and HDL-C levels were inversely correlated with the risk of GC. No association was observed between serum TG levels and the risk of GC. Similarly, no association was found between serum LDL-C levels and the risk of GC. [ABSTRACT FROM AUTHOR]

Specialized pro-resolving mediators (SPMs) have recently emerged as promising therapeutic approaches for neuropathic pain (NP). We evaluated the effects of oral treatment with the SPM Maresin 1 (MaR1) on behavioral pain responses and spinal neuroinflammation in male and female C57BL/6J mice with spared nerve injury (SNI)-induced NP. MaR1, or vehicle, was administered once daily, on post-surgical days 3 to 5, by voluntary oral intake. Sensory-discriminative and affective-motivational components of pain were evaluated with von Frey and place escape/avoidance paradigm (PEAP) tests, respectively. Spinal microglial and astrocytic activation were assessed by immunofluorescence, and the spinal concentration of cytokines IL-1β, IL-6, IL-10, and macrophage colony-stimulating factor (M-CSF) were evaluated by multiplex immunoassay. MaR1 treatment reduced SNI-induced mechanical hypersensitivity on days 7 and 11 in both male and female mice, and appeared to ameliorate the affective component of pain in males on day 11. No definitive conclusions could be drawn about the impact of MaR1 on the affective-motivational aspects of pain in female mice, since repeated suprathreshold mechanical stimulation of the affected paw in the dark compartment did not increase the preference of vehicle-treated SNI females for the light side, during the PEAP test session (a fundamental assumption for PAEP's validity). MaR1 treatment also reduced ipsilateral spinal microglial and astrocytic activation in both sexes and marginally increased M-CSF in males, while not affecting cytokines IL-1β, IL-6 and IL-10 in either sex. In summary, our study has shown that oral treatment with MaR1 (i) produces antinociception even in an already installed peripheral NP mouse model, and (ii) this antinociception may extend for several days beyond the treatment time-frame. These therapeutic effects are associated with attenuated microglial and astrocytic activation in both sexes, and possibly involve modulation of M-CSF action in males. [ABSTRACT FROM AUTHOR]

Fatty acids (FA) in follicular fluid (FF) are present in an esterified form [triglycerides, cholesterol esters and phospholipids] or as non-esterified FA, which partly originate from blood. However, a comprehensive comparison of blood vs. FF FA in various lipid classes is missing. The aim of this study was to determine the distribution of the FA composition in each lipid class of serum and FF, and to investigate their mutual correlations. A total of 74 patients undergoing assisted reproductive technology treatment were involved in the study. Both in serum as well as FF, saturated FA and mono-unsaturated FA were predominant in non-esterified FA and triglycerides fractions while poly-unsaturated FA were mainly present in phospholipids and cholesterol esters fractions, although phospholipids also contained high proportions of saturated FA. Irrespective of the lipid class, the FA proportions differed between serum and FF (P < 0.05). Despite these differences, most of the FA in triglycerides, phospholipids and cholesterol esters of FF were well correlated with their proportions in serum. Nevertheless, only weak to moderate associations (r < 0.60) were observed for the majority of the FA in the non-esterified FA fraction. Differences in FA product/precursor-ratios were found between serum and FF, such as higher C20:4n-6 to C18:2n-6 and C20:5n-3 to C18:3n-3 in FF. FA metabolism (e.g. desaturation and elongation) takes place in cells of the intrafollicular micro-environment. Moreover, good correlations between esterified FA in serum and FF suggest esterified FA in blood could be representative of esterified FA in FF. [ABSTRACT FROM AUTHOR]

Background: Lipids and glucose concentrations in the blood rise during pregnancy period. Poor control of these analytes results in cardio metabolic dysfunction. Despite this, there are no documented studies which investigate lipids and glucose among pregnant women in Tigrai, northern Ethiopia. Objective: The objective of this study was to assess lipid and glucose levels and identify their correlates among pregnant women in Tigrai, northern Ethiopia. Method: We conducted a facility-based cross sectional study comprising of systematically selected 200 pregnant women from July to October 2021. Those who were severely ill were excluded from the study. We used a structured questionnaire to collect socio-demographic and clinical characteristics of pregnant women. Lipids such as triglycerides, low density lipoprotein, cholesterol and blood glucose were also measured using Cobas C311 chemistry machine from plasma samples. The data were analyzed using SPSS version 25. Logistic regression was performed and statistical significance was declared at p-value < 0.05. Result: Proportion of pregnant women with cholesterol, triglyceride, low density lipoprotein and blood glucose levels above the upper limit of the normal range used for clinical decision were 26.5%, 43%, 44.5% and 21%, respectively. Pregnant women's income > = 10,000 ETB (AOR = 3.35; 95%CI: 1.46–7.66), age (AOR = 3.16; 95%CI: 1.03–9.68), gestational age 29–37 weeks (AOR = 8.02; 95%CI: 2.69–23.90) and having systolic blood pressure greater than 120 mmHg (AOR = 3.99; 95%CI: 1.64–9.75) demonstrated statistically significant association with raised levels of lipids. Conclusion and recommendation: Proportion of pregnant women with out of normal range values of lipids, particularly triglycerides and low density lipoprotein, is high. Gestational age is a strong predictor of increase in blood levels for both lipids. Provision of life style related health education and dietary intake to pregnant mothers matters. Moreover, monitoring lipid profile and glucose level during antenatal care period is essential. [ABSTRACT FROM AUTHOR]

The regulation of lipid stores is a central process for the physiology and ecology of fishes. Seasonal variation in lipid stores has been directly linked to survival of fishes across periods of food deprivation. We assessed whether a seasonally changing photoperiod was correlated to seasonal changes in energetic status to help better understand these important processes. Groups of first feeding Chinook salmon fry were introduced to a seasonal photoperiod cycle, but the point of entrance into the seasonal cycle varied from near the winter solstice (December), to either side of the spring equinox (February & May). Temperature and feeding rate were similar for all treatments. Subsequently, condition factor and whole body lipid content were assessed through a seasonal progression. Throughout most of the experiment, length and weight did not differ between the different photoperiod treatments, however whole body lipid and Fulton's condition factor did. Furthermore, changes in both whole body lipid and Fulton's condition factor in all treatment groups followed a similar seasonal pattern that was inversely related to day length (highest K and lipid levels found during days with the least light). These results suggest that regardless of age or size, there is a correlation between seasonal changes in photoperiod and changes in body composition in juvenile Chinook salmonids. [ABSTRACT FROM AUTHOR]

Objective: The risk of ischemic stroke with intracranial stenosis is associated with various serum lipid levels. However, the effects of changes in the lipid profile on the risk of in-stent restenosis have not been verified. Therefore, we investigated the association between the occurrence of in-stent restenosis at 12-month follow-up and changes in various lipid profiles. Methods: In this retrospective cohort study, we included ischemic stroke patients who had undergone intracranial stenting for symptomatic intracranial stenosis between February 2010 and May 2020. We collected data about serum low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), and triglyceride (TG) levels, and calculated the TC/HDL-C and LDL-C/HDL-C ratios at baseline and after 12 months. We conducted multivariable logistic regression analyses to verify the association between various lipid profile changes and in-stent restenosis at 12 months. Results: Among the 100 patients included in the study (mean age, 60.8 ± 10.0 years; male: 80 [80.0%]), in-stent restenosis was found in 13 (13.0%) patients. The risk of in-stent restenosis of more than 50% was significantly decreased when TC/HDL-C ratio (odds ratio [OR] 0.22, [95% confidence interval (CI) 0.05–0.87]) and LDL-C/HDL-C ratio (OR 0.23, [95% CI 0.06–0.93]) decreased or when HDL-C levels (OR 0.10, [95% CI 0.02–0.63]) were increased at 12 months compared with baseline measurements. Conclusions: Improvement of HDL-C levels, TC/HDL-C ratio, and LDL-C/HDL-C ratio were associated with decreased risk of in-stent restenosis at 12-month follow-up. Management and careful monitoring of various lipid profiles including HDL-C levels, TC/HDL-C ratio, and LDL-C/HDL-C ratio may be important to prevent in-stent restenosis in patients with intracranial stenting. [ABSTRACT FROM AUTHOR]

Algal extracts are sources of bioactive substances with applications in the development of novel alternative drugs against several diseases, including trichomoniasis sexually transmitted infection caused by Trichomonas vaginalis. Factors such as clinical failures and resistant strains limit the success of the existing drugs available for treating this disease. Therefore, searching for viable alternatives to these drugs is essential for the treatment of this disease. The present study was conducted for, in vitro and in silico characterization of extracts obtained from marine macroalgae Gigartina skottsbergii at stages gametophidic, cystocarpic, and tetrasporophidic. In addition, antiparasitic activity of these extracts against the ATCC 30236 isolate of T. vaginalis, their cytotoxicity, and gene expression of trophozoites after treatment were evaluated. The minimum inhibitory concentration and 50% inhibition concentration were determined for each extract. Results: In vitro analysis of the extracts' anti-T. vaginalis activity revealed an inhibitory effect of 100%, 89.61%, and 86.95% for Gigartina skottsbergii at stages gametophidic, cystocarpic, and tetrasporophidic, respectively, at 100 μg/mL. In silico analysis revealed the interactions between constituents of the extracts and enzymes from T. vaginalis, with significant free energy values obtained for the binding. None of the extract concentrations exhibited cytotoxic effects on VERO cell line compared to control, while cytotoxicity on HMVII vaginal epithelial cells line was observed at 100 μg/mL (30% inhibition). Gene expression analysis revealed differences in the expression profile of T. vaginalis enzymes between the extract-treated and control groups. According to these results, Gigartina skottsbergii extracts exhibited satisfactory antiparasitic activity. [ABSTRACT FROM AUTHOR]

Microalgal domestication is an expanding research field that aims to multiply and accelerate the potential of microalgae for various biotechnological purposes. We investigated the stability of improved lipid traits and genetic changes of a domesticated strain of the haptophyte Tisochrysis lutea, TisoS2M2, previously obtained by a mutation-selection improvement program. After 7 years of maintenance, TisoS2M2 still displayed improved lipid traits compared with the native strain, demonstrating that a mutation-selection improvement program is suitable for obtaining a domesticated strain with stable, improved phenotype over time. We identified specific genetic variations between the native and domesticated strains and focused on the dynamics of transposable elements (TEs). DNA transposons mainly caused specific TE indels of the domesticated strain TisoS2M2, and some specific TE indels may have impacted genes associated to the neutral lipid pathway. We revealed transposition events for TEs in T. lutea and discussed on the potential role of the improvement program on their activity. [ABSTRACT FROM AUTHOR]

Thermogenesis in brown adipose tissue (BAT) uses intracellular triglycerides, circulating free fatty acids and glucose as the main substrates. The objective of the current study was to analyse the role of CD36 fatty acid translocase in regulation of glucose and fatty acid utilisation in BAT. BAT isolated from spontaneously hypertensive rat (SHR) with mutant Cd36 gene and SHR-Cd36 transgenic rats with wild type variant was incubated in media containing labeled glucose and palmitate to measure substrate incorporation and oxidation. SHR-Cd36 versus SHR rats showed significantly increased glucose incorporation into intracellular lipids associated with reduced glycogen synthase kinase 3β (GSK-3β) protein expression and phosphorylation and increased oxidation of exogenous palmitate. It can be concluded that CD36 enhances glucose transport for lipogenesis in BAT by suppressing GSK-3β and promotes direct palmitate oxidation. [ABSTRACT FROM AUTHOR]

Kawasaki Disease (KD) is an acute inflammatory disorder associated with systemic vasculitis. Intravenous immunoglobulin (IVIG) is an effective therapy for KD, yet, about 20% of cases show IVIG resistance with persistent inflammation. The lipid profile in IVIG-resistant KD patients and the relationship between lipid characteristics and IVIG resistance remain unknown. In this study, serum samples from twenty KD patients with different IVIG responses (sensitive, intermediate, or resistant) were collected both before and after treatment, and lipidomic analysis was performed using high-performance liquid chromatography-mass spectrometry. As a result, before treatment, six lipid species were found as the most variant features, in which all the top decreased lipids in the IVIG-resistant group were lysophosphatidylcholine (LPC) and lysophosphatidylethanolamine (LPE), suggesting the potential to be IVIG-resistant markers in pretreatment diagnosis. During treatment, lipidomic changes showed a weaker response in the IVIG-resistant group. After treatment, LPC and LPE species exhibited lower in the IVIG-resistant group and negative correlation with the inflammatory markers, indicating that the unique metabolism may occur among IVIG-responsiveness. These results might contribute to diagnosing IVIG-resistant patients more accurately for alternative therapy and to a better understanding of how lipid metabolism is associated with IVIG sensitiveness/resistance in KD. [ABSTRACT FROM AUTHOR]

Intestinal ischemia-reperfusion injury leads to proinflammatory responses via gut-derived mediators, and accumulating evidence suggests that exosomes secreted by intestinal epithelial cells are involved in the development of systemic inflammation. Studies have reported changes in protein, lipid, and microRNA (miRNA) expression; however, considering the different experimental conditions, information on the relationships among these biomolecules remains insufficient. The aim of this study was to elucidate the multiple changes that simultaneously occur in exosomes after ischemic stimulation. Here, differentiated human intestinal Caco-2 cells were exposed to 95% air (normoxia group) or 5% O2 (hypoxia group) for 6 h. Cells in each group were subsequently incubated for 24 h in an atmosphere of 5% CO2 plus 95% air. The conditioned medium of each group was collected for isolating intestinal epithelial cell-derived exosomes. Together with proteome analyses, lipid analyses, and miRNA quantification, biological functional assays were performed using monocytic NF-κB reporter cells. Lipid metabolism-related protein expression was upregulated, miRNA levels were slightly altered, and unsaturated fatty acid-containing lysophosphatidylcholine concentration increased after hypoxia and reoxygenation injury; this suggested that the changes in exosomal components associated with ischemia-reperfusion injury activates inflammation, including the NF-κB pathway. This study elucidated the multiple changes that co-occur in exosomes after ischemic stimulation and partially clarified the mechanism underlying exosome-mediated inflammation after intestinal ischemic recanalization. [ABSTRACT FROM AUTHOR]

Atherosclerosis and cardiovascular events can be prevented, or treated, using statin therapy, either alone or in combination with ezetimibe. Chronic inflammation, vascular proliferation, and the development of atherosclerosis are also influenced by 25-hydroxycholesterol (25-OHC). The aim of the study was to compare the direct pleiotropic effects of two commonly-used statins (atorvastatin, rosuvastatin), ezetimibe, and their combinations, on the mRNA expression of pro-inflammatory IL1β, IL-18 and IL-23 and anti-inflammatory TGFβ, IL-35 (EBI3, IL-12 subunits), IL-10 and IL-37, in endothelial cells damaged by 25-OHC. It also analyzed IL-35 expression at the protein level. HUVECs were stimulated with atorvastatin (5 μM), rosuvastatin (10 μM), ezetimibe (1.22 μM), atorvastatin-ezetimibe (5 μM + 1.22 μM) or rosuvastatin-ezetimibe (10 μM + 1.22 μM), with or without pre-incubation with 10 μg/mL 25-OHC. mRNA expression was analyzed by real-time PCR. The protein level of IL-35 was analyzed by ELISA. In the pre-stimulated HUVECs, atorvastatin and rosuvastatin decreased mRNA expression of IL1β, IL-18, IL-23, TGFβ, IL35 and increased mRNA expression of IL-10 and IL-37 compared to 25-OHC. Furthermore, only incubation with rosuvastatin and rosuvastatin-ezetimibe decreased IL-35 mRNA and protein levels. Ezetimibe down-regulated only IL1β. Treatment with rosuvastatin-ezetimibe and atorvastatin-ezetimibe reversed the effect of 25-OHC in IL1β, IL-18 and IL-35 mRNA expression. In conclusion, rosuvastatin has the strongest anti-inflammatory effects and is the best at reducing the effect of oxysterols. Both statins exert a greater anti-inflammatory effect than ezetimibe. The anti-inflammatory effect of the combination therapies appears to be based on the effects of the statins alone and not their combination with ezetimibe. [ABSTRACT FROM AUTHOR]

It is well established that patients with Gaucher disease, as well as carriers of the disease have an increased risk for developing Parkinson's disease. A plethora of evidence suggests that disturbed α-Synuclein homeostasis is the link between Gaucher disease and Parkinson's disease. The pathogenic mechanism linking these entities is still a topic of debate and both gain- and loss-of-function theories have been put forward, which however are not mutually exclusive. In the present study we expanded our previous studies to include not only Gaucher disease patients but also Gaucher disease carriers and Gaucher disease patients following Enzyme Replacement Therapy. In these groups we investigated α-Synuclein in red blood cell membranes in association with lipid abnormalities described in Gaucher disease. These included glucosylceramide and its species, glucosylsphingosine, glucosylcholesterol and plasmalogens. Increased oligomerization of α-Synuclein in red blood cell membranes was observed not only in Gaucher disease patients but also in carriers of the disease. There were no qualitative differences in the lipids identified in the groups studied. However, significant quantitative differences compared to controls were observed in Gaucher disease patients but not in Gaucher disease carriers. Enzyme Replacement Therapy reversed the biochemical defects and normalized α-Synuclein homeostasis, providing for the first time evidence in human subjects that such homeostatic dysregulation is reversible. Further studies investigating α-Synuclein status during the differentiation of erythroid progenitors could provide new data on the pathogenic mechanism of α-Synuclein oligomerization in this system. [ABSTRACT FROM AUTHOR]

Purpose: To prospectively assess the effect of a single and regular application of either a cationic nanoemulsion of mineral oil (CN) or perfluorohexyloctane (F6H8) on the lipid layer of the tear film and higher order aberrations (HOA) in patients with Dry Eye Disease (DED). Methods: Fifty-seven patients with a lipid layer thickness (LLT) ≤ 75 interferometric colour units (ICU) were included in the study. In group A (20 patients) the effect of a single drop of F6H8 or CN on HOA and LLT was assessed immediately after application and up to two hours later. For long term effects (Group B) 37 patients applied CN or F6H8 five times a day for 12 weeks. Measurement of LLT, HOA, non-invasive-tear-break-up-time (NIBUT) and meibography were assessed prior to as well as at 4 weeks and 12 weeks after initiation of treatment. Our study is registered in the "German Clinical Trials Register" under the trial number: DRKS00028696. Results: CN led to an increase of the LLT from 46.8 ± 16.9 ICU to 76.3 ± 23.5 ICU (p = 0.021) and to an increase of HOA from 0.43 ± 0.06 μm to 0.48 ± 0.08 μm immediately after application (p = 0.027). There was no correlation between the increase of LLT and HOA (r = -0.04; p = 0.90). In group B an increase of LLT was observed in the F6H8 group from 45.8 ± 8.8 ICU at baseline to 66.7 ± 19.5 ICU at 12 weeks (p = 0.002). No changes of HOA were measured throughout the observation period in group B. After 12 weeks CN increased NIBUT from 9.9 ± 5.3 seconds to 15.5 ± 5.6 seconds (p = 0.04). F6H8 increased NIBUT from 12.4 ± 5.9 seconds to 16.9 ± 4.7 seconds (p = 0.02) after 12 weeks. Conclusion: CN leads to a short-term increase in LLT and HOA, but only immediately after application. In contrast F6H8 does lead to an increase of LLT after regular long-term use but has no effect on HOA. The regular application of lipid-based products does not seem to decrease the quality of vision as measured in HOA. Instead, CN and F6H8, both are able to stabilize the tear film after regular application. [ABSTRACT FROM AUTHOR]

Background and aims: The LDL cholesterol (LDL-C) treatment goals recommended by the 2019 ESC/EAS guidelines are only achieved in a minority of patients. The study objective was to estimate the impact of bempedoic acid treatment on LDL-C target attainment, drug costs, and atherosclerotic cardiovascular disease (ASCVD) events. The simulation used a Monte Carlo approach in a representative cohort of German outpatients at high or very-high cardiovascular risk. Additionally to statins, consecutive treatment with ezetimibe, bempedoic acid, and a PCSK9 inhibitor was simulated in patients not achieving their LDL-C goal. Considered were scenarios without and with bempedoic acid (where bempedoic acid was replaced by a PCSK9 inhibitor when LDL-C was not controlled). Results: The simulation cohort consisted of 105,577 patients, of whom 76,900 had very-high and 28,677 high cardiovascular risk. At baseline, 11.2% of patients achieved their risk-based LDL-C target. Sequential addition of ezetimibe and bempedoic acid resulted in target LDL-C in 33.1% and 61.9%, respectively. Treatment with bempedoic acid reduced the need for a PCSK9 inhibitor from 66.6% to 37.8% and reduced drug costs by 35.9% per year on stable lipid-lowering medication. Compared to using only statins and ezetimibe, this approach is projected to prevent additional 6,148 ASCVD events annually per 1 million patients, whereas PCSK9 inhibition alone would prevent 7,939 additional ASCVD events annually. Conclusions: A considerably larger proportion of cardiovascular high- and very-high-risk patients can achieve guideline-recommended LDL-C goals with escalated lipid-lowering medication. Bempedoic acid is projected to substantially decrease the need for PCSK9 inhibitor treatment to achieve LDL-C targets, associated with reduced drug costs albeit with fewer prevented events. [ABSTRACT FROM AUTHOR]

P5A ATPases are expressed in the endoplasmic reticulum (ER) of all eukaryotic cells, and their disruption results in pleiotropic phenotypes related to severe ER stress. They were recently proposed to function in peptide translocation although their specificity have yet to be confirmed in reconstituted assays using the purified enzyme. A general theme for P-type ATPases is that binding and transport of substrates is coupled to hydrolysis of ATP in a conserved allosteric mechanism, however several independent reports have shown purified Spf1p to display intrinsic spontaneous ATP hydrolytic activity after purification. It has never been determined to what extend this spontaneous activity is caused by uncoupling of the enzyme. In this work we have purified a functional tagged version of the Saccharomyces cerevisiae P5A ATPase Spf1p and have observed that the intrinsic ATP hydrolytic activity of the purified and re-lipidated protein can be stimulated by specific detergents (C12E8, C12E10 and Tween20) in mixed lipid/detergent micelles in the absence of any apparent substrate. We further show that this increase in activity correlate with the reaction temperature and the anisotropic state of the mixed lipid/detergent micelles and further that this correlation relies on three highly conserved phenylalanine residues in M1. This suggests that at least part of the intrinsic ATP hydrolytic activity is allosterically coupled to movements in the TM domain in the purified preparations. It is suggested that free movement of the M1 helix represent an energetic constraint on catalysis and that this constraint likely is lost in the purified preparations resulting in protein with intrinsic spontaneous ATP hydrolytic activity. Removal of the N-terminal part of the protein apparently removes this activity. [ABSTRACT FROM AUTHOR]

Aim: In United Arab Emirates, cardiovascular disease (CVD) is a leading cause of mortality and 22% of CVD deaths are attributable to acute myocardial infarction (MI). Adherence to guidelines for lipid management is incompletely described in the Middle East. This study aimed to characterize lipid lowering therapy (LLT) patterns and the risk of subsequent cardiovascular events (CVEs) in the first year after MI. Methods: This was a retrospective cohort study using the Dubai Real-World Claims Database, including all patients discharged with MI between January 01, 2015 and December 31, 2018, followed-up until December 31, 2019. Results: In the first year after MI, 8.42% of 4,595 patients included experienced at least one recurrent MI (rate 6.77 events/100 person-years [PYs]), 2.94% had one revascularization (cumulative rate 0.55 events/100 PYs) and 2.66% had one hospitalization due to unstable angina (cumulative rate 5.16 new events/100 PYs). The majority (60.40%) of the patients presented with LDL-C levels ≥ 70 mg/dL after MI. In the first year after MI, 93.45% of the patients received LLT, mainly high-intensity statin (67.79%); with a minority of patients receiving statin + ezetimibe (4.55%), PCSK9i (0.20%) or ezetimibe alone (0.07%). Conclusion: Patients hospitalized with MI in Dubai present an increased risk of CVEs in their first-year post-discharge. Majority of the patients presented with LDL-C levels above 70 mg/dL, which indicates suboptimal lipid control with existing LLT, particularly in high-risk patients. [ABSTRACT FROM AUTHOR]

Psychological problems commonly experienced by patients with type 2 diabetes mellitus (T2DM) cause diabetes fatigue conditions that can further worsen the treatment prognosis. We conducted this investigation to determine the effectiveness of a resilience-based Islamic program on diabetes fatigue and health-related quality of life (HRQoL) by measuring the biochemical indicators of T2DM. This was a quasi-experimental study performed from May to August 2021, in which 80 respondents aged 18–64 years diagnosed with T2DM were included through purposive sampling at a male:female sex ratio of 1:1 in the control group and 17:23 in the treatment group. A resilience-based Islamic program (a combination of stress management, mindfulness, prayer, and dhikr (the ritual formula of Sufi brotherhood recited devotionally in praise of Allah and as a means of attaining ecstatic experience)) was implemented in the treatment group for six sessions by blended online and offline interventions. Multidimensional Fatigue Inventory-20 and World Health Organization Quality of Life, Brief Form were used to evaluate diabetes fatigue and HRQoL. Blood tests were performed to measure HbA1c, total antioxidant serum, insulin, cholesterol, triglyceride, high-density lipoprotein cholesterol (HDL-c), and low-density lipoprotein cholesterol (LDL-c) levels from baseline to 3 months. Statistical analyses were conducted using paired t test, Wilcoxon signed-rank test, independent t test, and Mann–Whitney U test. The resilience-based Islamic program had a beneficial impact on the levels of HbA1c (p < 0.001), lipid profile (triglyceride) (p = 0.011), HDL-c (p = 0.01), LDL-c (p < 0.001), total antioxidant serum (p = 0.001), insulin (p < 0.001), diabetes fatigue (p < 0.05), and HRQoL (p < 0.05) in patients of the treatment group. The results of biochemical tests related to T2DM also indicated a reduction in diabetes fatigue and an increase in HRQoL due to the resilience-based Islamic program. Considering that a patient's resilience to diabetes is an important factor in the management of diabetes fatigue, the resilience-based Islamic program can be applied at public health centers and community levels to increase T2DM resilience. [ABSTRACT FROM AUTHOR]

Background: Despite lipid-lowering and antiplatelet therapy, the pattern of residual lipoproteins seems relevant to long-term cardiovascular outcomes. This study aims to evaluate the effects of combined therapies, commonly used in subjects with acute myocardial infarction, in the quality of low-density lipoprotein (LDL) particles. Methods: Prospective, open-label trial, included patients with acute myocardial infarction. Patients were randomized to antiplatelet treatment (ticagrelor or clopidogrel) and subsequently to lipid-lowering therapy (rosuvastatin or simvastatin/ezetimibe) and were followed up for six months. Nonlinear optical properties of LDL samples were examined by Gaussian laser beam (Z-scan) to verify the oxidative state of these lipoproteins, small angle X-ray scattering (SAXS) to analyze structural changes on these particles, dynamic light scattering (DLS) to estimate the particle size distribution, ultra violet (UV)-visible spectroscopy to evaluate the absorbance at wavelength 484 nm (typical from carotenoids), and polyacrylamide gel electrophoresis (Lipoprint) to analyze the LDL subfractions. Results: Simvastatin/ezetimibe with either clopidogrel or ticagrelor was associated with less oxidized LDL, and simvastatin/ezetimibe with ticagrelor to lower cholesterol content in the atherogenic subfractions of LDL, while rosuvastatin with ticagrelor was the only combination associated with increase in LDL size. Conclusions: The quality of LDL particles was influenced by the antiplatelet/lipid-lowering strategy, with ticagrelor being associated with the best performance with both lipid-lowering therapies. Trial registration: NCT02428374. [ABSTRACT FROM AUTHOR]

Pregnant and lactating women have been discouraged from using cannabis by Health Canada. However, the increasing rate of cannabis use among pregnant women has presented an urgent need to investigate its physiological effects during the perinatal period. During pregnancy, the mammary gland (MG) undergoes remodeling, which involves alveolar differentiation of mammary epithelial cells (MECs), which is essential for breast milk production and secretion. Limited evidence has been reported on the impact of cannabis or its components, delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), on MG development or MEC differentiation. In this study, we investigated the effects of THC and CBD on the differentiation of MECs by assessing changes in cellular viability, lipid accumulation, and gene and protein expression of major milk protein and lipid synthesizing markers. using the HC11 cells as a model. We hypothesized that THC and CBD will negatively impact the synthesis of milk proteins and lipids, as well as lipid markers in HC11 cells. Our results demonstrated that THC and CBD reduced cellular viability at concentrations above 30μM and 20μM, respectively. Relative to control, 10μM THC and 10μM CBD reduced mRNA levels of milk proteins (CSN2 and WAP), lipid synthesizing and glucose transport markers (GLUT 1, HK2, FASN, FABP4, PLIN2 and LPL), as well as whey acidic protein and lipid levels. In addition, co-treatment of a CB2 antagonist with THC, and a CB2 agonist with CBD, reversed the impact of THC and CBD on the mRNA levels of key markers, respectively. In conclusion, 10μM THC and CBD altered the differentiation of HC11 cells, in part via the CB2 receptor. [ABSTRACT FROM AUTHOR]

Halocynthia aurantium is a marine organism that has been considered a promising source for bio-functional materials. Total lipids were extracted from H. aurantium tunic, and then they were separated into neutral lipids, glycolipids, and phospholipids. In the present study, fatty acid profiles of three lipids and their anti-inflammatory effects in RAW264.7 cells were investigated. Among the lipid classes, phospholipids showed the diversity of fatty acid constituents, compared with the glycolipids and neutral lipids. Three lipids contain different contents of fatty acids depending on the kinds of lipids. The most contents were saturated fatty acids (SFAs, 53–69% of the fatty acids) and monounsaturated fatty acids (MUFAs, 15–17% of fatty acids) and polyunsaturated fatty acids (PUFAs, 14–32% of fatty acids) are followed. H. aurantium lipids not only dose-dependently inhibited nitric oxide production but also reduced the expression of inflammatory cytokine genes such as TNF-α, IL-1β, and IL-6 in LPS-stimulated macrophages. It was also demonstrated that the expression of COX-2 was dose-dependently suppressed. Moreover, H. aurantium lipids decreased phosphorylation of NF-κB p-65, p38, ERK1/2, and JNK, suggesting that three lipids from H. aurantium tunic provide anti-inflammatory effects through NF-κB and MAPK signaling. These results indicate that H. aurantium is a potential source for anti-inflammation. [ABSTRACT FROM AUTHOR]

Chronic hepatitis B virus (HBV) infection is characterized by the presence of high circulating levels of non-infectious lipoprotein-like HBV surface antigen (HBsAg) particles thought to contribute to chronic immune dysfunction in patients. Lipid and metabolomic analysis of humanized livers from immunodeficient chimeric mice (uPA/SCID) revealed that HBV infection dysregulates several lipid metabolic pathways. Small molecule inhibitors of lipid biosynthetic pathway enzymes acetyl-CoA carboxylase (ACC), fatty acid synthase, and subtilisin kexin isozyme-1/site-1 protease in HBV-infected HepG2-NTCP cells demonstrated potent and selective reduction of extracellular HBsAg. However, a liver-targeted ACC inhibitor did not show antiviral activity in HBV-infected liver chimeric mice, despite evidence of on-target engagement. Our study suggests that while HBsAg production may be dependent on hepatic de novo lipogenesis in vitro, this may be overcome by extrahepatic sources (such as lipolysis or diet) in vivo. Thus, a combination of agents targeting more than one lipid metabolic pathway may be necessary to reduce HBsAg levels in patients with chronic HBV infection. [ABSTRACT FROM AUTHOR]

Lipid ratios and the triglyceride and glucose index (TyG) could be a simple biochemical marker of insulin resistance (IR). The current study was carried out to examine the correlation between triglyceride to high-density lipoprotein-cholesterol (TG/HDL-C), total cholesterol to HDL-C (TC/HDL-C), low-density lipoprotein-cholesterol to HDL-C ratio (LDL-C/HDL-C), as well as TyG index with the severity and mortality of severe coronavirus disease 2019 (COVID-19). A total of 1228 confirmed COVID-19 patients were included in the current research. Regression models were performed to evaluate the correlation between the lipid index and severity and mortality of COVID-19. The TyG index and TG/HDL-C levels were significantly higher in the severe patients (P<0.05). TG/HDL-C, LDL-C/HDL-C, TC/HDL-C ratios, and TyG index were significantly lower in survivor cases (P<0.05). Multivariate logistic regression analysis demonstrated that predictors of the severity adjusted for age, sex and BMI were TyG index, TG/HDL-C ratio (OR = 1.42 CI:1.10–1.82, OR = 1.06 CI: 1.02–1.11, respectively). This analysis showed that TG/HDL-C, TC/HDL-C, LDL-C/HDL-C ratios, and TyG index statistically are correlated with COVID-19 mortality (OR = 1.12 CI:1.06–1.18, OR = 1.24 CI:1.05–1.48, OR = 1.47 CI:1.19–1.80, OR = 1.52 CI:1.01–2.31, respectively). In summary, the TyG index and lipid ratios such as TC/HDL-C, TG/HDL-C, LDL-C/HDL-C could be used as an early indicator of COVID-19 mortality. Furthermore, the study revealed that TyG index and TG/HDL-C indices are biochemical markers of COVID-19 severe prognosis. [ABSTRACT FROM AUTHOR]

Introduction: Information on LDL's dynamic behaviour of LDL (i.e. production rate and fractional catabolic rate) are of interest if pathologies, lipid-lowering strategies or LDL-metabolism itself are investigated. Determination of these rates is costly and elaborate. Here we studied the interrelationship of LDL mass, its composition and other lipoproteins. Based on this data, we deducted information about LDL's dynamic behaviour. Methods: Lipoprotein profiles of n = 236 participants are evaluated. Plasma was separated by sequential ultracentrifugation into VLDL, IDL, LDL and HDL. Additionally, LDL and HDL were separated into subfractions. Stepwise multiple linear regressions were used to study LDL's ApoB mass and lipid composition. Relying on these results and on causation, we constructed a mathematical model to estimate LDL's retention time. Results: The ApoB mass in LDL correlated best among all measured parameters (including corresponding lipid compositions but using no LDL-associated parameters) with the cholesterol ester content in IDL. TG/CE ratios in LDL's subfractions were strongly correlated with the corresponding ratios in IDL and HDL. The constructed mathematical model links the TG/CE ratio of LDL and HDL to LDL's ApoB concentration and enables a good estimate of LDL's retention time in plasma. Discussion: Relying on our statistic evaluations, we assume that i) the production of nascent LDL via IDL as well as ii) LDL's prolonged retention are mapped by the TG/CE ratio in LDL subfractions. HDL's TG/CE ratio is associated with the change in LDL's TG/CE ratio during its retention in plasma. Our mathematical model uses this information and enables–by relying on causation- a good estimation of LDL's retention time. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to evaluate the correlation between tear film lipid layer thickness and transepidermal water loss (TEWL) from the ocular area in patients with short tear break-up time (TBUT)-type dry eye and healthy controls. Methods: This prospective study included 25 eyes of patients with short TBUT-type dry eye disease and 25 eyes of healthy controls. Results: Tear film lipid layer thickness was measured using an interferometer, and TEWL from the ocular area was measured using a Tewameter TM300 with custom-made goggles. The correlation between tear film lipid layer thickness and TEWL was evaluated. Additionally, other parameters such as TBUT, Schirmer I score, ocular surface staining, the presence and type of meibomian gland dysfunction (MGD), ocular surface disease index (OSDI), and visual analog scale (VAS) scores were evaluated. Tear film lipid layer thickness did not show a significant correlation with TEWL from the ocular area measured using a Tewameter TM300. However, tear film lipid layer thickness was significantly correlated with tear break-up time (p = 0.004) and ocular surface staining by NEI (National Eye Institute) scheme (p = 0.03). TEWL showed positive correlation with the Schirmer I score (p = 0.004). Conclusions: The tear film lipid layer affected the stability of the tear film more than the amount of TEWL in patients with short TBUT dry eye and healthy controls. [ABSTRACT FROM AUTHOR]

The preventive effects of regular exercise on obesity-related health problems are carried over to the non-exercise detraining period, even when physical activity decreases with aging. However, it remains unknown whether regular childhood exercises can be carried over to adulthood. Therefore, this study aimed to investigate the effects of long-term childhood exercise and detraining on lipid accumulation in organs to prevent obesity in adulthood. Four-week-old male Otsuka Long-Evans Tokushima Fatty (OLETF) rats were used as obese animals. OLETF rats were allocated into sedentary and exercise groups: exercise from 4- to 12-week-old and detraining from 12- to 20-week-old. At 12-week-old immediately after the exercise period, regular exercise completely inhibited hyperphagia, obesity, enlarged pancreatic islets, lipid accumulation and lobular inflammation in the liver, hypertrophied adipocytes in the white adipose tissue (WAT), and brown adipose tissue (BAT) whitening in OLETF rats. Additionally, exercise attenuated the decrease in the ratio of muscle wet weight to body weight associated with obesity. Decreased food consumption was maintained during the detraining period, which inhibited obesity and diabetes at 20-week-old after the detraining period. Histologically, childhood exercise inhibited the enlargement of pancreatic islets after the detraining period. In addition, inhibition of lipid accumulation was completely maintained in the WAT and BAT after the detraining period. However, the effectiveness was only partially successful in lipid accumulation and inflammation in the liver. The ratio of muscle wet weight to body weight was maintained after detraining. In conclusion, early long-term regular exercise effectively prevents obesity and diabetes in childhood, and its effectiveness can be tracked later in life. The present study suggests the importance of exercise during childhood and adolescence to inhibit hyperphagia-induced lipid accumulation in metabolic-related organs in adulthood despite exercise cessation. [ABSTRACT FROM AUTHOR]

In addition to statin therapy, Ezetimibe, a non-statin lipid-modifying agent, is increasingly used to reduce low-density lipoprotein cholesterol and atherosclerotic cardiovascular disease risk. Literature suggests the clinical effectiveness of Ezetimibe plus statin (EPS) therapy; however, primary evidence on its economic effectiveness is inconsistent. Hence, we pooled incremental net benefit to synthesise the cost-effectiveness of EPS therapy. We identified economic evaluation studies reporting outcomes of EPS therapy compared with other lipid-lowering therapeutic agents or placebo by searching PubMed, Embase, Scopus, and Tufts Cost-Effective Analysis registry. Using random-effects meta-analysis, we pooled Incremental Net Benefit (INB) in the US $ with a 95% confidence interval (CI). We used the modified economic evaluations bias checklist and GRADE quality assessment for quality appraisal. The pooled INB from twenty-one eligible studies showed that EPS therapy was significantly cost-effective compared to other lipid-lowering therapeutic agents or placebo. The pooled INB (95% CI) was $4,274 (621 to 7,927), but there was considerable heterogeneity (I2 = 84.21). On subgroup analysis EPS therapy is significantly cost-effective in high-income countries [$4,356 (621 to 8,092)], for primary prevention [$4,814 (2,523 to 7,106)], and for payers' perspective [$3,255 (571 to 5,939)], and from lifetime horizon [$4,571 (746 to 8,395)]. EPS therapy is cost-effective compared to other lipid-lowering therapeutic agents or placebo in high-income countries and for primary prevention. However, there is a dearth of evidence from lower-middle-income countries and the societal perspective. [ABSTRACT FROM AUTHOR]

Dynamic physical examination data can provide both cross-sectional and time-series characteristics of cardiovascular health. However, most physical examination databases containing health and disease information have not been fully utilized in China. Hence, this study aimed to analyze dynamic physical examination indicators for cardiovascular health to provide evidence for precise prevention and control of cardiovascular diseases in the primary prevention domain among healthy population with different demographic characteristics in Shanghai. Three-year continuous data were collected from the physical examination center of a hospital in Shanghai from 2018 to 2020, which included a total of 14,044 participants with an average age of 46.51±15.57 years. The cardiovascular status of overall healthy individuals may have a decreasing trend, which is manifested as a significant year-on-year decrease in high-density lipoprotein cholesterol; a significant year-on-year increase in total cholesterol, low-density lipoprotein cholesterol, and blood glucose levels; and a possible increasing trend of diastolic blood pressure, body mass index, and triglycerides. Healthy population with different sex and age groups have various sensitives to cardiovascular physical examination indicators. To conduct more accurate cardiovascular health management and health promotion for key populations in primary prevention, focusing on the dynamic trends of blood pressure, blood lipids, blood glucose, and body mass index in men and changes in total cholesterol in women over time is especially important. The age group of 50–69 years is key for better prevention and control of cardiovascular health. [ABSTRACT FROM AUTHOR]

Background: Progressive fibrous thickening of peritoneal membrane (PM) is a major complication of long-term peritoneal dialysis. TGF-β/SMAD pathway activation, inflammation and neoangiogenesis have an important role in PM changes induced by peritoneal dialysis. Here, we investigated the effects of paclitaxel (PTX) carried in lipid core nanoparticles (LDE) on the development of peritoneal fibrosis (PF) in rats. Methods: To induce PF, 21 male Wistar rats (300-350g) were injected with chlorhexidine gluconate for 15 consecutive days and randomly assigned to three groups: 1)PF, n = 5: no treatment; 2)LDE, n = 8: treated with LDE only, 3/3 days during 15 days; 3)LDE-PTX, n = 8: treated with PTX (4mg/kg) associated with LDE, 3/3 days during 15 days. A Control group without PF induction (n = 5) was designed, received saline solution, 3/3 days. Peritoneum function tests were performed, and anterior abdominal wall samples of the PM were collected for analyses of peritoneal thickness, immunohistochemitry, and gene expression. Results: LDE-PTX treatment preserved the membrane function, maintaining the ultrafiltration rate and mass transfer of glucose at normal levels. LDE-PTX also prevented PM thickening induced by chlorhexidine gluconate injections. LDE-PTX treatment reduced the number of myofibroblasts infiltrating PM and inhibited the cell proliferation. Gene expression of fibronectin, FSP-1, VEGF, TGF-β, and SMAD3 were reduced by LDE-PTX. Conclusions: LDE-PTX was effective to prevent development of PF and preserve the PM filtration capacity in this rat model, with clear-cut actions on pro-fibrotic mechanisms. Thus, LDE-PTX can be candidate for future clinical trials as adjuvant to peritoneal dialysis to prevent PF development, since this preparation is devoid of toxicity as shown previously. [ABSTRACT FROM AUTHOR]

Cardiolipin is known to interact with bacterial and mitochondrial proteins and protein complexes. Unlike in Escherichia coli and Saccharomyces cerevisiae, the synthesis of cardiolipin is essential for growth of Trypanosoma brucei parasites in culture. Inhibition of cardiolipin production has been shown to result in major changes in the T. brucei proteome and energy metabolism, with CLDP43, a mitochondrial protein containing a StaR-related lipid transfer (START)-like domain, being depleted in a cardiolipin-dependent way. We now show that in T. brucei procyclic forms lacking CLDP43, cardiolipin metabolism and mitochondrial function are affected. Using quantitative and qualitative lipid analyses, we found that while steady-state levels of cardiolipin were elevated in CLDP43 knock-out parasites compared to parental cells, de novo formation of cardiolipin was down-regulated. In addition, depletion of CLDP43 resulted in partial loss of mitochondrial membrane potential and decreased ATP production via substrate level phosphorylation. Recombinant CLDP43 was found to bind cardiolipin and phosphatidic acid in lipid overlay experiments, suggesting that it may be involved in transport or synthesis of cardiolipin or its precursors in T. brucei. [ABSTRACT FROM AUTHOR]

The degree of maintaining nutrient intake patterns, conformed in the family, for offspring into adulthood is unknown. The aim of this study was to investigate the correlation between nutrient intakes in three younger-middle-older generations of Tehranian adults by sex. Of individuals who participated in 2012–15 phase of the Tehran Lipid and Glucose Study, 1286 families (4685 subjects), who had at least two members of the family with complete data in two or three generations were entered in this cross-sectional study. The energy and nutrient intakes of parents and their young or adult offspring or grandparents-grandson/granddaughter dyads were compared. The differences were estimated using pairwise t-test and partial correlation. Data of parents with their offspring were paired based on living arrangement. There were 857 fathers (mean age: 55.4±11.1) and 1394 mothers (mean age: 50.1±11.4). The mean age of grandfathers and grandmothers were 69.4±7.9 and 63.7±8.5 respectively. The significant correlation in fathers-sons and father-daughter (living with their parents) pairs were observed for 9 and 7 nutrients, respectively. Correlations for most nutrients were significant for mother-daughter or sons (living with their parents) dyads. The mean percentage of energy from total fat and trans-fatty acids of sons or daughters (living with their parents) were higher than their parents. For most nutrients, there were no significant adjusted correlations between parents-adult offspring (living independent of their parents) dyads. Also few nutrient intakes of grandparents-grandson or granddaughter dyads were correlated. The nutrient intakes of adult offspring were not associated with their parents; this correlation for younger and older generations disappeared. There were weak to moderate correlation between nutrient intakes of parent-offspring dyads that lived with their parents. The resemblance was higher for mother-offspring than father-offspring. Overall, total fat and trans-fatty acid intakes of young offspring were higher than their parents. [ABSTRACT FROM AUTHOR]

Gestational diabetes mellitus (GDM) is one of the most common complications of pregnancy but the underlying mechanism remains obscure. The aims of this study are to examine if omental adipose tissue (OMAT) and subcutaneous AT (SCAT) differentially express proinflammatory and lipid metabolic adipokines, and if so, whether their regional differences have implications on lipid metabolism in GDM. Paired samples of OMAT and SCAT were excised from pregnant women in scheduled Cesarean sections with non-obese (NOBS), obese (OBS) and GDM. The results showed that the mRNA of monocyte chemoattractant protein (MCP)-1, macrophage marker CD68, and cytokines IL-6, IL-8, and TNF-α are increased in OMAT from GDM women compared to that in NOBS and OBS women (P<0.05). Glucose and TNF-α dose-dependently enhanced ADM and its receptor components CRLR and RAMPs in human adipocytes. Immunofluorescence showed that ADM and its receptor components are higher in OMAT from GDM women compared to non-GDM women. Further, basal lipolysis was greater in OMAT than in SCAT and ADM stimulates further glycerol release in OMAT, but not in SCAT, and these increases are reduced by ADM antagonist, ADM22-52. We therefore conclude that elevated ADM and its receptor expressions by OMAT, but not by SCAT appear to contribute to the lipid dysregulation in GDM women, and manipulation of ADM may represent one of the novel approaches in minimizing the risk of GDM-related fetal overgrowth. [ABSTRACT FROM AUTHOR]

In this work, the Longissimus thoracis pig skeletal muscle was used as a model to investigate the impact of two different diets, supplemented with n-3 polyunsaturated fatty acids from extruded linseed (L) and polyphenols from grape skin and oregano extracts (L+P), on the lipidomic profile of meat. A standard diet for growing-finishing pigs (CTRL) was used as a control. Changes in lipids profile were investigated through an untargeted lipidomics and transcriptomics combined investigation. The lipidomics identified 1507 compounds, with 195 compounds fitting with the MS/MS spectra of LipidBlast database. When compared with the CTRL group, the L+P diet significantly increased 15 glycerophospholipids and 8 sphingolipids, while the L diet determined a marked up-accumulation of glycerolipids. According to the correlations outlined between discriminant lipids and genes, the L diet may act preventing adipogenesis and the related inflammation processes, while the L+P diet promoted the expression of genes involved in lipids' biosynthesis and adipogenic extracellular matrix formation and functioning. [ABSTRACT FROM AUTHOR]

While fatty acid metabolism is altered under physiological conditions, alterations can also be maladaptive in diseases such as diabetes and heart failure. Peroxisome Proliferator Activated Receptor α (PPARα) is a transcription factor that regulates fat metabolism but its role in regulating lipid storage in the heart is unclear. The aim of this study is to improve our understanding of how cardiac PPARα regulates cardiac health and lipid accumulation. To study the role of cardiac PPARα, tamoxifen inducible cardiac-specific PPARα knockout mouse (cPPAR-/-) were treated for 5 days with tamoxifen and then studied after 1–2 months. Under baseline conditions, cPPAR-/- mice appear healthy with normal body weight and mortality is not altered. Importantly, cardiac hypertrophy or reduced cardiac function was also not observed at baseline. Mice were fasted to elevate circulating fatty acids and induce cardiac lipid accumulation. After fasting, cPPAR-/- mice had dramatically lower cardiac triglyceride levels than control mice. Interestingly, cPPAR-/- hearts also had reduced Plin2, a key protein involved in lipid accumulation and lipid droplet regulation, which may contribute to the reduction in cardiac lipid accumulation. Overall, this suggests that a decline in cardiac PPARα may blunt cardiac lipid accumulation by decreasing Plin2 and that independent of differences in systemic metabolism a decline in cardiac PPARα does not seem to drive pathological changes in the heart. [ABSTRACT FROM AUTHOR]