Acids In Adipose Tissue Research Articles

Fatty Acids in Subcutaneous Adipose Tissue of Pregnant Women with and without Polycystic Ovary Syndrome Are Associated with Genes Related to Steroidogenesis: A Case-Control Study.

The qualitative analysis of adipose tissue (AT) is an exciting area for research and clinical applications in several diseases and it is emerging along with the quantitative approach to research on overweight and obese people. While the importance of steroid metabolism in women with polycystic ovary syndrome (PCOS) has been reported, limited data exists on the effective roles of AT in pregnant women suffering from PCOS. The aim of this study was to determine association of fatty acid (FA) profiles with expression of 14 steroid genes in abdominal subcutaneous AT of PCOS vs. non-PCOS pregnant women. In this case-control study, the AT samples of 36 non-PCOS pregnant women and 12 pregnant women with PCOS (3:1 ratio control: case) who underwent cesarean section were collected. Relationship of expressing gene targets and different features were performed using Pearson correlation analysis on the R 3.6.2 software. The ggplot2 package in R tool was used to draw the plots. Age (31.4 and 31.5 years, P=0.99), body mass index (BMI) (prior pregnancy 26 and 26.5 kg.m-2, P=0.62) and at delivery day (30.1 and 31, P=0.94), gestational period (264 and 267 days, P=0.70) and parity (1.4 and 1.4, P=0.42) of non-PCOS and PCOS pregnant women were similar. Expression of steroidogenic acute regulator (STAR) and 11β-Hydroxysteroid dehydrogenase (11BHSD2) in non-PCOS pregnant women showed the highest association with eicosapentaenoic acid (EPA, C20:5 n-3, r=0.59, P=0.001) and (r=0.66, P=0.001), respectively. In the all participants, STAR mRNA level showed the greatest association with the EPA fatty acid concentration (P=0.001, r=0.51). Our results showed a link between the genes involved in steroid metabolism and fatty acids in AT of pregnant women, especially for omega-3 FA and the gene involved in the first step of steroidogenesis in subcutaneous AT. These findings warrant further studies.

Metabolic Action of Metformin

Metformin, a cheap and safe biguanide derivative, due to its ability to influence metabolism, is widely used as a first-line drug for type 2 diabetes (T2DM) treatment. Therefore, the aim of this review was to present the updated biochemical and molecular effects exerted by the drug. It has been well explored that metformin suppresses hepatic glucose production in both AMPK-independent and AMPK-dependent manners. Substantial scientific evidence also revealed that its action is related to decreased secretion of lipids from intestinal epithelial cells, as well as strengthened oxidation of fatty acids in adipose tissue and muscles. It was recognized that metformin’s supra-therapeutic doses suppress mitochondrial respiration in intestinal epithelial cells, whereas its therapeutic doses elevate cellular respiration in the liver. The drug is also suggested to improve systemic insulin sensitivity as a result of alteration in gut microbiota composition, maintenance of intestinal barrier integrity, and alleviation of low-grade inflammation.

Omega-3 fatty acids in adipose tissue and risk of atrial fibrillation.

The aim of the present study was to examine the relation between adipose tissue content of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and the risk of incident atrial fibrillation (AF). In this case-cohort study based on data from the Danish Diet, Cancer and Health cohort, a total of 5255 incident cases of AF was identified during 16.9years of follow-up. Adipose tissue biopsies collected at baseline from all cases and from a randomly drawn subcohort of 3440 participants were determined by gas chromatography. Data were analysed using weighted Cox regression. Data were available for 4741 incident cases of AF (2920 men and 1821 women). Participants in the highest vs. the lowest quintile of EPA experienced a 45% lower risk of AF (men HR 0.55 (95% CI 0.41-0.69); women HR 0.55 (0.41-0.72)). For DHA, no clear association was found in men, whereas in women, participants in the highest quintile of DHA in adipose tissue had a 30% lower risk of incident AF (HR 0.70 (0.54-0.91)) compared to participants in the lowest quintile. A monotonous inverse association was found for the content of EPA in adipose tissue and risk of AF in both men and women. The content of DHA was inversely associated with the risk of AF in women, whereas no clear association was found for men.

Linoleic acid in adipose tissue and the risk of myocardial infarction: a case-cohort study.

We investigated risk of myocardial infarction (MI) associated with the content of linoleic acid (LA) in adipose tissue, a biomarker of long-term dietary intake of LA and a marker of endogenous LA exposure. Between 1993 and 1997, 57,053 middle-aged subjects were included in the Danish Diet, Cancer and Health cohort. We performed a case-cohort study that included a random sample of the full cohort (n = 3167) and all incident MI cases appearing during 16years of follow-up (n = 2819). Information on incident MI cases was obtained by linkage with Danish nationwide registries. Adipose tissue biopsies were taken from the buttocks of the participants, and their fatty acid composition was determined using gas chromatography. HRs (hazard ratios) with 95% confidence intervals (CIs) were used to describe the associations between content of LA in adipose tissue and the risk of MI. HRs were calculated using weighted Cox proportional hazards regression with robust variance. After adjustment for established risk factors of MI, adipose tissue content of LA was not associated with the risk of MI in men and women combined (quintiles 5 versus 1, HR, 1.03 (95% CI, 0.85-1.25), P-trend = 0.970) or in men and women separately (quintiles 5 versus 1, HR, 1.05 (95% CI, 0.83-1.33), P-trend = 0.871 and quintiles 5 versus 1, HR, 0.99 (95% CI 0.72-1.37), P-trend = 0.928, respectively). Investigating the association between LA and MI with a shorter, 5- or 10-year duration of follow-up provided similar results. Content of LA in adipose tissue was not associated with the risk of MI.

Hormone-sensitive lipase: sixty years later

Hormone-sensitive lipase (HSL) was initially characterized as the hormonally regulated neutral lipase activity responsible for the breakdown of triacylglycerols into fatty acids in adipose tissue. This review aims at providing up-to-date information on structural properties, regulation of expression, activity and function as well as therapeutic potential. The lipase is expressed as different isoforms produced from tissue-specific alternative promoters. All isoforms are composed of an N-terminal domain and a C-terminal catalytic domain within which a regulatory domain containing the phosphorylation sites is embedded. Some isoforms possess additional N-terminal regions. The catalytic domain shares similarities with bacteria, fungus and vascular plant proteins but not with other mammalian lipases. HSL singularity is provided by regulatory and N-terminal domains sharing no homology with other proteins. HSL has a broad substrate specificity compared to other neutral lipases. It hydrolyzes acylglycerols, cholesteryl and retinyl esters among other substrates. A novel role of HSL, independent of its enzymatic function, has recently been described in adipocytes. Clinical studies revealed dysregulations of HSL expression and activity in disorders, such as lipodystrophy, obesity, type 2 diabetes and cancer-associated cachexia. Development of specific inhibitors positions HSL as a pharmacological target for the treatment of metabolic complications.

Lipolysis modulates the biosynthesis of inflammatory lipid mediators derived from linoleic acid in adipose tissue of periparturient dairy cows

Oxidized linoleic acid metabolites (OXLAM) are products of adipocyte lipolysis with the potential to modulate adipose tissue (AT) lipid metabolism and inflammation. In periparturient cows, linoleic acid is preferentially mobilized from AT during lipolysis by hormone-sensitive lipase (HSL) compared with other polyunsaturated fatty acids. Enzymatic and nonenzymatic reactions generate OXLAM from linoleic acid. Among OXLAM, 9-, 10-, and 12-hydroxy-octadecadienoic acids (HODE) are associated with pro-inflammatory responses, whereas 9- and 13-oxo-octadecadienoic acids (oxoODE) and 13-HODE can facilitate inflammation resolution and promote lipogenesis. This study evaluated the effect of HSL activity on OXLAM biosynthesis using subcutaneous AT explants collected from multiparous dairy cows at 10 d before and again at 10 and 24 d after calving. Explants were treated for 3 h without or with the β-adrenergic agonist isoproterenol (ISO; 1 µM; MilliporeSigma, Burlington, MA) to induce HSL activity. The contribution of HSL to OXLAM biosynthesis was determined by inhibiting its activity with CAY10499 (2 µM; Cayman Chemical, Ann Arbor, MI). After treatments, media and explants were collected for lipidomic analysis using HPLC-tandem mass spectroscopy. Results indicated that ISO increased the biosynthesis of 9-, 12-, and 13-HODE and 9-oxoODE, and this effect was reduced at 24 d after calving. Inhibiting HSL activity partially reversed ISO effects on HODE and 9-oxoODE. Our ex vivo model demonstrated for the first time a direct effect of HSL activity on the biosynthesis of OXLAM in AT, especially at 10 d before and 10 d after calving. The biosynthesis of anti-inflammatory OXLAM is limited during the first weeks after parturition and may promote AT inflammation and lipolytic responses to negative energy balance. These results indicate that HSL activity releases linoleic acid for OXLAM biosynthesis in concentrations of a magnitude that may bypass the need for the activation of phospholipases linked with the inflammatory cascade and thus supports, in part, lipolysis-driven inflammation within AT of periparturient cows.

Adipocyte ACLY Facilitates Dietary Carbohydrate Handling to Maintain Metabolic Homeostasis in Females

SUMMARYSugars and refined carbohydrates are major components of the modern diet. ATP-citrate lyase (ACLY) is upregulated in adipocytes in response to carbohydrate consumption and generates acetyl-coenzyme A (CoA) for both lipid synthesis and acetylation reactions. Here, we investigate the role of ACLY in the metabolic and transcriptional responses to carbohydrates in adipocytes and unexpectedly uncover a sexually dimorphic function in maintaining systemic metabolic homeostasis. When fed a high-sucrose diet, AclyFAT−/− females exhibit a lipodystrophy-like phenotype, with minimal fat accumulation, insulin resistance, and hepatic lipid accumulation, whereas AclyFAT−/− males have only mild metabolic phenotypes. We find that ACLY is crucial for nutrient-dependent carbohydrate response element-binding protein (ChREBP) activation in adipocytes and plays a key role, particularly in females, in the storage of newly synthesized fatty acids in adipose tissue. The data indicate that adipocyte ACLY is important in females for the systemic handling of dietary carbohydrates and for the preservation of metabolic homeostasis.

TLR2 and TLR4 mediate an activation of adipose tissue renin-angiotensin system induced by uric acid

Both hyperuricemia and adipose tissue renin–angiotensin system (RAS) are closely associated with multiple metabolic and cardiovascular diseases. We previously reported that uric acid could upregulate tissue RAS in adipocytes. In the present study, we aimed to reveal the involvement of toll-like receptors (TLRs) in uric acid-induced RAS activation in adipose tissue. A hyperuricemia rat model fed with a high-fructose diet and rat primary adipocytes were used in this study. Here, we inhibited TLR2 and TLR4 expression in adipose tissue and cultured adipocytes using small interfering RNA (siRNA). We found that high fructose-fed rats had hyperuricemia, higher body weight and greater adipose tissue content. We also found that hyperuricemia rats had raising blood pressure, higher expression levels of inflammatory cytokines and RAS components in adipose tissue, which could be prevented by TLR2/4-siRNA infection. In vitro study, uric acid caused a dose- and time-dependent increase in the mRNA expression of TLR2 and TLR4 in rat adipocytes. Uric acid could increase inflammatory cytokines and upregulate tissue RAS in rat adipocytes, which were both blocked with TLR2/4-siRNA infection. TNF-α and IL-6 could also result in an activation of tissue RAS expression in adipocytes. In conclusion, TLR2/4 mediated adipose inflammation plays a key role in RAS activation induced by uric acid in adipose tissue.

High Fiber Diet Suppression of TLR4 and NFκβ Gene Expression Correlated with TNF-α and IL-6 Levels in Hypertriglyceridemia Rats

Hypertriglyceridemia causes hypoxia and increases the release of free fatty acids in adipose tissue through lipolysis which stimulates an increase in TLR4 and NFκβ levels as well as TNF-α and IL-6 secretion. The high fiber diet had a suppressing effect against TLR4 and NFκβ gene expression and decreased TNF-α and IL-6 levels. This study evaluated the effect of high fiber diet (P1= 1.04 g content of fiber/rat/day, P2= 2.07 g content of fiber /rat/day and P3= 3.11 g content of fiber/rat/day) on TNF-α and IL-6 levels as well as expression of TLR4 and NFκβ in rats induced by high fat and fructose diet for 6 weeks. The findings indicate that the administration of high fiber diet to the hypertriglyceridemia rats could control body weight gain and significantly reduce TNF-α and IL-6 levels (pp<0.05) when compared with the normal and hypertriglyceridemia groups. The suppression of TLR4 and NFκβ were correlated with TNF-α and IL-6 levels. In conclusion, the administration of the high fiber diet to the hypertriglyceridemia rats was able to decrease TNF-α and IL-6 levels possibly by suppression of TLR4 and NFκB gene expression.

Patterns of adipose tissue fatty acids and the risk of atrial fibrillation: A case-cohort study.

Fatty acids in adipose tissue share dietary sources and metabolic pathways and therefore occur in patterns. The aim of the present study was to investigate the association between adipose tissue fatty acid patterns identified by the data-driven dimension-reducing method treelet transform and the risk of atrial fibrillation. A total of 57,053 Danish men and women aged 50–64 years participating in the Diet, Cancer and Health cohort had an adipose tissue biopsy taken at baseline. During a median follow-up of 14.6 years, a total of 4,710 participants developed atrial fibrillation or atrial flutter. Adipose tissue biopsies were analysed for fatty acid content by gas chromatography for all cases of atrial fibrillation and for a randomly drawn subcohort (n = 3,500) representative for the entire cohort. Hazard ratios with 95% confidence intervals for atrial fibrillation according to quintiles of factor scores were determined by weighted Cox proportional hazards regression analyses for men and women separately. From the 32 fatty acids measured, 7 major factors/patterns of fatty acids were identified using treelet transform. We found that a pattern consisting of n-6 polyunsaturated fatty acids (PUFA) (except linoleic acid) was associated with a lower hazard of atrial fibrillation. Patterns consisting of marine n-3 PUFA and containing n-9 fatty acids were associated with a lower hazard of atrial fibrillation in women. In conclusion, patterns of fatty acids in adipose tissue identified by treelet transform may be differentially associated with the risk of atrial fibrillation.

Sociodemographic, Anthropometric, and Dietary Predictors of Polyunsaturated Fatty Acids in Adipose Tissue Among Mesoamerican Children and Their Parents.

Polyunsaturated fatty acid (PUFA) intake is low throughout Latin America. Improving PUFA status could be an effective intervention against chronic disease, but information on sociodemographic and dietary patterning of PUFA status in the region is limited. To characterize sociodemographic, anthropometric, and dietary predictors of PUFA status biomarkers in adipose tissue among children and their parents from Mesoamerica. This was a cross-sectional study of 220 children aged 7 to 12 years and 471 parents from capital cities of Guatemala, El Salvador, the Dominican Republic, Honduras, Nicaragua, Panama, Costa Rica, and Belize, as well as Tuxtla Gutiérrez in Mexico. The PUFA from gluteal adipose tissue was quantified using gas chromatography. Participants reported sociodemographic information and the type of vegetable oil used for cooking. We estimated percent mean differences in linoleic acid (LA), total long-chain n-6 PUFA (n-6 LCPUFA), α-linolenic acid (ALA), and total long-chain n-3 PUFA (n-3 LCPUFA) between levels of predictors using multivariable-adjusted linear regression models. Country was the strongest predictor of any PUFA, whereas body mass index was positively associated with n-6 LCPUFA in children and adults. Cooking primarily with soybean oil was positively associated with LA in children and adults and ALA in adults. Cooking with canola oil was positively related to n-6 LCPUFA in adults and n-3 LCPUFA in children and adults. Cooking with palm oil was associated with low adipose tissue levels of all n-6 and n-3 PUFA. Adipose tissue PUFA status in Mesoamerica is associated with country of origin and the type of oil used for cooking.

Omega-6 vegetable oils as a driver of coronary heart disease: the oxidized linoleic acid hypothesis

The intake of omega-6 vegetable oils, particularly soybean oil, began to increase in the USA starting in the early 1900s at a time when the consumption of butter and lard...

G protein-coupled receptor 120 in mediating the regulation effect of saturated and unsaturated long-chain fatty acid on human adipocytes

ObjectiveTo explore G protein-coupled receptor 120 (GPR120)'s role in mediating saturated and unsaturated long-chain fatty acid on adipocyte inflammation, ER stress and insulin signaling pathway. MethodsOmental adipose tissue from 5 patients undergoing elective gallstone removal surgery was collected and the primary adipocytes were isolated and cultured. In the first experiment, cells were divided into the following four groups: (1) Control group; (2): Docosahexaenoic acid (DHA) group; (3)DHA+10 μmol/L GW9508 group; and (4) DHA+20 μmol/L GW9508 group. In the second experiment, cells were divided into the following four groups:(1) Control group; (2) Palmic acid (PA) group; (3) PA+10 μmol/L GW9508 group; and (4) PA+20 μmol/L GW9508 group. Real time PCR and western blot were used to evaluate the gene and protein expression of GPR120, FABP4, inflammatory factors and ER stress markers. Results(1) Under the stimulation of DHA and PA, the expression of GPR and FABP4 were increased. But with inhibition of GPR120, the expression of GPR120and FABP4 decreased in both DHA and PA treatment groups.(2) DHA treatment could decrease TNF-alpha expression and inflammation factor mRNA levels in primary adipocytes. Production of these factors increased with inhibition of GPR120. PA treatment could increase TNF-alpha expression and inflammation factor mRNA levels in primary adipocytes. They were further increased by inhibition of GPR120. (3) DHA treatment could decrease ER stress in primary adipocytes. GPR120 inhibition could promote ER stress. PA treatment could increase ER stress in primary adipocytes. Again, GPR120 inhibition further increased ER stress. Conclusion GPR120 mediated long-chain fatty acid-related inflammation and ER stress regulation, and balanced the function of saturated and unsaturated long-chain fatty acid in adipose tissue.

Trans fatty acids in adipose tissue and risk of myocardial infarction: A case-cohort study.

BackgroundThe risk of coronary heart disease associated with intake of individual trans fatty acids (TFAs) is not clear. Adipose tissue content of TFAs is a biomarker of TFA intake and metabolism.ObjectiveWe investigated the rate of myocardial infarction (MI) associated with the adipose tissue content of total 18:1t, isomers of 18:1t (18:1 Δ6-10t and 18:1 Δ11t) and 18:2 Δ9c, 11t.MethodsA case-cohort study, nested within the Danish Diet, Cancer and Health cohort (n = 57,053), was conducted, which included a random sample (n = 3156) of the total cohort and all incident MI cases (n = 2148) during follow-up (14 years). Information on MI cases was obtained by linkage with nationwide registers and validated. Adipose tissue was taken from the participants buttocks and the fatty acid composition was determined by gas chromatography.ResultsWomen with higher adipose tissue content of total 18:1t had a 57% higher MI rate (quintiles 5 versus 1, hazard ratio, 1.57; 95% confidence interval, 1.12–2.20; P-trend = 0.011) and women with higher content of 18:1 Δ6-10t had a 76% higher MI rate (quintiles 5 versus 1, hazard ratio, 1.76; 95% confidence interval, 1.23–2.51; P-trend = 0.002). No association between 18:1 Δ11t content and MI rate was observed. In men, no associations between adipose tissue content of total 18:1t and 18:1 Δ6-10t and MI rate were observed. However, men with higher content of 18:1 Δ11t had a 48% higher MI rate (quintiles 5 versus 1, hazard ratio, 1.48; 95% confidence interval, 1.17–1.86; P-trend = 0.003). Adipose tissue content of 18:2 Δ9c, 11t was not associated with MI rate in women or men.ConclusionsAdipose tissue content of 18:2 Δ9c, 11t was not associated with MI rate in women or men, whereas higher contents of isomers of 18:1t were associated with higher MI rates but the associations for individual 18:1t isomers differed, however, in women and men.

Linoleic Acid in Adipose Tissue and Development of Ischemic Stroke: A Danish Case-Cohort Study.

BackgroundWe investigated the association between the content of linoleic acid in adipose tissue, a biomarker of long‐term intake of linoleic acid, and the risk of ischemic stroke and its subtypes.Methods and ResultsThe Danish cohort study Diet, Cancer and Health included 57 053 patients aged 50 to 65 years at enrollment. All participants had an adipose tissue biopsy performed at enrollment, while information on ischemic stroke during follow‐up was obtained from the Danish National Patient Register. Stroke diagnoses were all validated and classified according to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification. Cases and a randomly drawn subcohort of 3500 patients had their fatty acid composition in adipose tissue determined by gas chromatography. Hazard ratios with 95% confidence intervals were calculated using weighted Cox proportional hazard regression. During 13.5 years of follow‐up, 1879 ischemic stroke cases were identified, for which 1755 adipose biopsies were available, while adipose biopsies were available for 3203 participants in the subcohort. When comparing the highest and the lowest quartiles of adipose tissue content of linoleic acid there was a negative association with the rate of total ischemic stroke (hazard ratio, 0.78; 95% confidence interval, 0.65–0.93) and large artery atherosclerosis (hazard ratio, 0.61; 95% confidence interval, 0.43–0.88), while there was an indication of a negative association with small‐vessel occlusion (hazard ratio, 0.87; 95% confidence interval, 0.69–1.11). There was no clear association with the rate of cardioembolism.ConclusionsThe content of linoleic acid in adipose tissue was inversely associated with the risk of total ischemic stroke and stroke caused by large artery atherosclerosis.

Effects of full fat rice bran and defatted rice bran on growth performance and carcass characteristics of growing-finishing pigs.

The objective was to test the hypothesis that increasing inclusion levels of full fat rice bran (FFRB) or defatted rice bran (DFRB) are not detrimental to growth or carcass characteristics, longissimus muscle (LM) quality, or fat quality when fed to growing-finishing pigs. A total of 224 barrows and gilts were randomly allotted to 7 treatments, with 4 pigs per pen and 8 pen replicates per treatment. Pigs had an average initial BW of 28.2 ± 4.1 kg and a 3-phase feeding program was used. A basal diet containing corn and soybean meal, 3 diets containing corn, soybean meal, and 10, 20, or 30% FFRB, and 3 diets containing corn, soybean meal, and 10, 20, or 30% DFRB were formulated within each phase. Daily feed allotments and pig BW at the start of the experiment and at the conclusion of each phase were recorded. On the last day of the experiment, 1 pig per pen was harvested and carcass characteristics, LM quality, and fat quality were determined. For the overall experimental period, no effects of dietary treatments were observed for average daily gain. However, average daily feed intake (ADFI) decreased (linear, P < 0.05) and gain to feed ratio (G:F) increased (linear, P < 0.05) for pigs fed diets with increasing concentrations of FFRB. In contrast, ADFI increased linearly (P < 0.05) and G:F decreased (linear, P < 0.05) as DFRB was included in the diets. There were no effects of dietary treatments on LM quality. The length of the bellies decreased (linear and quadratic, P < 0.05) as the inclusion of FFRB or DFRB increased in the diets. The concentration of crude fat in the adipose tissue of pigs increased linearly (P < 0.05) as the concentration of FFRB or DFRB increased in the diets. The concentration of saturated fatty acids in the adipose tissue of pigs fed diets containing FFRB decreased (linear, P < 0.05), whereas the concentration of polyunsaturated fatty acids (PUFA) increased (linear, P < 0.05). In contrast, addition of DFRB did not affect the concentration of fatty acids in adipose tissues. In conclusion, 30% FFRB included in diets for growing-finishing pigs may improve G:F without affecting carcass characteristics or LM quality with the exception that PUFA in adipose tissues will increase. However, inclusion of DFRB in diets for growing-finishing pigs will reduce G:F without affecting the LM quality or composition of adipose tissues.

WITHDRAWN: G protein-coupled receptor 120 in mediating the regulation effect of saturated and unsaturated long-chain fatty acid on human adipocytes

Abstract Objective To explore G protein-coupled receptor 120 (GPR120)'s role in mediating saturated and unsaturated long-chain fatty acid on adipocyte inflammation, ER stress and insulin signaling pathway. Methods Omental adipose tissue from 5 patients undergoing elective gallstone removal surgery was collected and the primary adipocytes were isolated and cultured. In the first experiment, cells were divided into the following four groups: (1) Control group; (2): Docosahexaenoic acid (DHA) group; (3)DHA+10 μmol/L GW9508 group; and (4) DHA+20 μmol/L GW9508 group. In the second experiment, cells were divided into the following four groups:(1) Control group; (2) Palmic acid (PA) group; (3) PA+10 μmol/L GW9508 group; and (4) PA+20 μmol/L GW9508 group. Real time PCR and western blot were used to evaluate the gene and protein expression of GPR120, FABP4, inflammatory factors and ER stress markers. Results (1) Under the stimulation of DHA and PA, the expression of GPR and FABP4 were increased. But with inhibition of GPR120, the expression of GPR120and FABP4 decreased in both DHA and PA treatment groups.(2) DHA treatment could decrease TNF-alpha expression and inflammation factor mRNA levels in primary adipocytes. Production of these factors increased with inhibition of GPR120. PA treatment could increase TNF-alpha expression and inflammation factor mRNA levels in primary adipocytes. They were further increased by inhibition of GPR120. (3) DHA treatment could decrease ER stress in primary adipocytes. GPR120 inhibition could promote ER stress. PA treatment could increase ER stress in primary adipocytes. Again, GPR120 inhibition further increased ER stress. Conclusion GPR120 mediated long-chain fatty acid-related inflammation and ER stress regulation, and balanced the function of saturated and unsaturated long-chain fatty acid in adipose tissue.

Adipocyte ACLY Facilitates Dietary Carbohydrate Handling and Protects Against Insulin Resistance in Females

Sugars and refined carbohydrates are major components of the modern diet. ATP-citrate lyase (ACLY) is upregulated in adipocytes in response to carbohydrate consumption and generates acetyl-CoA for both lipid synthesis and acetylation reactions. Here we investigated the role of ACLY in the metabolic and transcriptional responses to carbohydrates in adipocytes, and unexpectedly uncovered a sexually dimorphic function in maintaining systemic metabolic homeostasis. When fed a high sucrose diet, AclyFAT-/- females exhibit a lipodystrophy-like phenotype, with minimal fat accumulation, insulin resistance, and hepatic lipid accumulation, while AclyFAT-/- males have only mild metabolic phenotypes. We find that ACLY is crucial for nutrientdependent ChREBP activation in adipocytes and plays a key role particularly in females in the storage of newly synthesized fatty acids in adipose tissue. The data indicate that adipocyte ACLY is important in females for the systemic handling of dietary carbohydrates and for the preservation of metabolic homeostasis.

Oleate ameliorates palmitate-induced reduction of NAMPT activity and NAD levels in primary human hepatocytes and hepatocarcinoma cells

BackgroundNicotinamide phosphoribosyltransferase (NAMPT) and nicotinamide adenine dinucleotide (NAD) levels are crucial for liver function. The saturated fatty acid palmitate and the unsaturated fatty acid oleate are the main free fatty acids in adipose tissue and human diet. We asked how these fatty acids affect cell survival, NAMPT and NAD levels in HepG2 cells and primary human hepatocytes.MethodsHepG2 cells were stimulated with palmitate (0.5mM), oleate (1mM) or a combination of both (0.5mM/1mM) as well as nicotinamide mononucleotide (NMN) (0.5 mM) or the specific NAMPT inhibitor FK866 (10nM). Cell survival was measured by WST-1 assay and Annexin V/propidium iodide staining. NAD levels were determined by NAD/NADH Assay or HPLC. Protein and mRNA levels were analysed by Western blot analyses and qPCR, respectively. NAMPT enzyme activity was measured using radiolabelled 14C–nicotinamide. Lipids were stained by Oil red O staining.ResultsPalmitate significantly reduced cell survival and induced apoptosis at physiological doses. NAMPT activity and NAD levels significantly declined after 48h of palmitate. In addition, NAMPT mRNA expression was enhanced which was associated with increased NAMPT release into the supernatant, while intracellular NAMPT protein levels remained stable. Oleate alone did not influence cell viability and NAMPT activity but ameliorated the negative impact of palmitate on cell survival, NAMPT activity and NAD levels, as well as the increased NAMPT mRNA expression and secretion. NMN was able to normalize intracellular NAD levels but did not ameliorate cell viability after co-stimulation with palmitate. FK866, a specific NAMPT inhibitor did not influence lipid accumulation after oleate-treatment.ConclusionsPalmitate targets NAMPT activity with a consequent cellular depletion of NAD. Oleate protects from palmitate-induced apoptosis and variation of NAMPT and NAD levels. Palmitate-induced cell stress leads to an increase of NAMPT mRNA and accumulation in the supernatant. However, the proapoptotic action of palmitate seems not to be mediated by decreased NAD levels.

P433Linoleic acid in adipose tissue and risk of ischemic stroke

P433Linoleic acid in adipose tissue and risk of ischemic stroke