BACKGROUND: The role of fatty acids (FA) in the pathogenesis of insulin resistance and hyperlipidemia is a subject of intensive research. Several recent works have suggested cis-vaccenic acid (cVA) in plasma lipid compartments, especially in plasma phospholipids (PL) or erythrocyte membranes, could be associated with markers of insulin sensitivity and cardiovascular health. Nevertheless, not all the results of research work testify to these beneficial effects of cVA. Therefore, we decided to investigate the relations of proportion of cVA in plasma PL to markers of insulin resistance in hyperlipidemic men. SUBJECTS: In 231 men (median age 50) with newly diagnosed hyperlipidemia, we analyzed basic clinical parameters together with FA composition of plasma PL and stratified them according to the content of cVA into upper quartile (Q4) and lower quartile (Q1) groups. We examined also small control group of 50 healthy men. RESULTS: The individuals in Q4 differed from Q1 by lower plasma insulin (p < 0.05), HOMA-IR values (p < 0.01), and apolipoprotein B concentrations (p < 0.001), but by the higher total level of nonesterified FA (p < 0.01). Both groups had similar age, anthropometrical, and other lipid parameters. In plasma PL, the Q4 group had lower content of the sum of n-6 polyunsaturated FA, due to decrease of γ-linolenic and dihomo-γ-linolenic acids, whereas the content of monounsaturated FA (mainly oleic and palmitoleic) was in Q4 higher. CONCLUSIONS: Our results support hypothesis that plasma PL cVA could be associated with insulin sensitivity in men with hyperlipidemia.

• MeSH
• apolipoproteiny B krev   MeSH
• biologické markery * krev   MeSH
• dospělí MeSH
• fosfolipidy * krev   MeSH
• hyperlipidemie * krev   MeSH
• inzulin krev   MeSH
• inzulinová rezistence * MeSH
• kyseliny olejové * krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• apolipoproteiny B MeSH
• biologické markery * MeSH
• cis-vaccenic acid MeSH Prohlížeč
• fosfolipidy * MeSH
• inzulin MeSH
• kyseliny olejové * MeSH

In mammals, the white adipocyte is a cell type that is specialized for storage of energy (in the form of triacylglycerols) and for energy mobilization (as fatty acids). White adipocyte metabolism confers an essential role to adipose tissue in whole-body homeostasis. Dysfunction in white adipocyte metabolism is a cardinal event in the development of insulin resistance and associated disorders. This Review focuses on our current understanding of lipid and glucose metabolic pathways in the white adipocyte. We survey recent advances in humans on the importance of adipocyte hypertrophy and on the in vivo turnover of adipocytes and stored lipids. At the molecular level, the identification of novel regulators and of the interplay between metabolic pathways explains the fine-tuning between the anabolic and catabolic fates of fatty acids and glucose in different physiological states. We also examine the metabolic alterations involved in the genesis of obesity-associated metabolic disorders, lipodystrophic states, cancers and cancer-associated cachexia. New challenges include defining the heterogeneity of white adipocytes in different anatomical locations throughout the lifespan and investigating the importance of rhythmic processes. Targeting white fat metabolism offers opportunities for improved patient stratification and a wide, yet unexploited, range of therapeutic opportunities.

• MeSH
• bílé tukové buňky metabolismus   MeSH
• homeostáza MeSH
• lidé MeSH
• management nemoci * MeSH
• metabolismus lipidů fyziologie   MeSH
• obezita metabolismus   terapie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

Branched esters of palmitic acid and hydroxystearic acid (PAHSA) are anti-inflammatory and antidiabetic lipokines that connect glucose and lipid metabolism. We aimed to characterize involvement of the 5-PAHSA regioisomer in the adaptive metabolic response of white adipose tissue (WAT) to cold exposure (CE) in mice, exploring the cross talk between glucose utilization and lipid metabolism. CE promoted local production of 5- and 9-PAHSAs in WAT. Metabolic labeling of de novo lipogenesis (DNL) using 2H2O revealed that 5-PAHSA potentiated the effects of CE and stimulated triacylglycerol (TAG)/fatty acid (FA) cycling in WAT through impacting lipogenesis and lipolysis. Adipocyte lipolytic products were altered by 5-PAHSA through selective FA re-esterification. The impaired lipolysis in global adipose triglyceride lipase (ATGL) knockout mice reduced free PAHSA levels and uncovered a metabolite reservoir of TAG-bound PAHSAs (TAG estolides) in WAT. Utilization of 13C isotope tracers and dynamic metabolomics documented that 5-PAHSA primes adipocytes for glucose metabolism in a different way from insulin, promoting DNL and impeding TAG synthesis. In summary, our data reveal new cellular and physiological mechanisms underlying the beneficial effects of 5-PAHSA and its relation to insulin action in adipocytes and independently confirm a PAHSA metabolite reservoir linked to ATGL-mediated lipolysis.

• MeSH
• bílá tuková tkáň metabolismus   MeSH
• glukosa metabolismus   MeSH
• izotopy uhlíku MeSH
• kyselina palmitová metabolismus   MeSH
• kyseliny stearové metabolismus   MeSH
• lipasa genetika   metabolismus   MeSH
• lipogeneze genetika   MeSH
• lipolýza MeSH
• mastné kyseliny metabolismus   MeSH
• metabolomika MeSH
• myši knockoutované MeSH
• myši MeSH
• nízká teplota MeSH
• oxid deuteria MeSH
• triglyceridy metabolismus   MeSH
• tukové buňky metabolismus   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 5-PAHSA MeSH Prohlížeč
• 9-PAHSA MeSH Prohlížeč
• glukosa MeSH
• izotopy uhlíku MeSH
• kyselina palmitová MeSH
• kyseliny stearové MeSH
• lipasa MeSH
• mastné kyseliny MeSH
• oxid deuteria MeSH
• PNPLA2 protein, mouse MeSH Prohlížeč
• triglyceridy MeSH

Fatty acid esters of hydroxy fatty acids (FAHFAs) are lipid mediators with promising antidiabetic and anti-inflammatory properties that are formed in white adipose tissue (WAT) via de novo lipogenesis, but their biosynthetic enzymes are unknown. Using a combination of lipidomics in WAT, quantitative trait locus mapping, and correlation analyses in rat BXH/HXB recombinant inbred strains, as well as response to oxidative stress in murine models, we elucidated the potential pathway of biosynthesis of several FAHFAs. Comprehensive analysis of WAT samples identified ∼160 regioisomers, documenting the complexity of this lipid class. The linkage analysis highlighted several members of the nuclear factor, erythroid 2 like 2 (Nrf2)-mediated antioxidant defense system (Prdx6, Mgst1, Mgst3), lipid-handling proteins (Cd36, Scd6, Acnat1, Acnat2, Baat), and the family of flavin containing monooxygenases (Fmo) as the positional candidate genes. Transgenic expression of Nrf2 and deletion of Prdx6 genes resulted in reduction of palmitic acid ester of 9-hydroxystearic acid (9-PAHSA) and 11-PAHSA levels, while oxidative stress induced by an inhibitor of glutathione synthesis increased PAHSA levels nonspecifically. Our results indicate that the synthesis of FAHFAs via carbohydrate-responsive element-binding protein-driven de novo lipogenesis depends on the adaptive antioxidant system and suggest that FAHFAs may link activity of this system with insulin sensitivity in peripheral tissues.

• MeSH
• bílá tuková tkáň enzymologie   metabolismus   MeSH
• biologické markery metabolismus   MeSH
• estery chemie   metabolismus   MeSH
• faktor 2 související s NF-E2 genetika   metabolismus   MeSH
• krysa rodu Rattus MeSH
• kyselina palmitová chemie   metabolismus   MeSH
• kyseliny stearové chemie   metabolismus   MeSH
• metabolomika metody   MeSH
• myši inbrední C57BL MeSH
• myši knockoutované MeSH
• náhodné rozdělení MeSH
• oxidační stres * MeSH
• peroxiredoxin VI genetika   metabolismus   MeSH
• potkani inbrední BN MeSH
• potkani inbrední SHR MeSH
• potkani transgenní MeSH
• regulace genové exprese enzymů * MeSH
• stanovení celkové genové exprese MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 9-hydroxystearic acid MeSH Prohlížeč
• biologické markery MeSH
• estery MeSH
• faktor 2 související s NF-E2 MeSH
• kyselina palmitová MeSH
• kyseliny stearové MeSH
• Nfe2l2 protein, mouse MeSH Prohlížeč
• Nfe2l2 protein, rat MeSH Prohlížeč
• peroxiredoxin VI MeSH
• Prdx6 protein, mouse MeSH Prohlížeč

Nutrigenomics investigates relationships between nutrients and all genome-encoded molecular entities. This holistic approach requires systems biology to scrutinize the effects of diet on tissue biology. To decipher the adipose tissue (AT) response to diet induced weight changes we focused on key molecular (lipids and transcripts) AT species during a longitudinal dietary intervention. To obtain a systems model, a network approach was used to combine all sets of variables (bio-clinical, fatty acids and mRNA levels) and get an overview of their interactions. AT fatty acids and mRNA levels were quantified in 135 obese women at baseline, after an 8-week low calorie diet (LCD) and after 6 months of ad libitum weight maintenance diet (WMD). After LCD, individuals were stratified a posteriori according to weight change during WMD. A 3 steps approach was used to infer a global model involving the 3 sets of variables. It consisted in inferring intra-omic networks with sparse partial correlations and inter-omic networks with regularized canonical correlation analysis and finally combining the obtained omic-specific network in a single global model. The resulting networks were analyzed using node clustering, systematic important node extraction and cluster comparisons. Overall, AT showed both constant and phase-specific biological signatures in response to dietary intervention. AT from women regaining weight displayed growth factors, angiogenesis and proliferation signaling signatures, suggesting unfavorable tissue hyperplasia. By contrast, after LCD a strong positive relationship between AT myristoleic acid (a fatty acid with low AT level) content and de novo lipogenesis mRNAs was found. This relationship was also observed, after WMD, in the group of women that continued to lose weight. This original system biology approach provides novel insight in the AT response to weight control by highlighting the central role of myristoleic acid that may account for the beneficial effects of weight loss.

• MeSH
• dospělí MeSH
• genové regulační sítě genetika   MeSH
• hmotnostní úbytek genetika   fyziologie   MeSH
• kalorická restrikce * MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• obezita metabolismus   MeSH
• stanovení celkové genové exprese MeSH
• tuková tkáň metabolismus   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Fatty acid composition of adipose tissue changes with weight loss. Palmitoleic acid as a possible marker of endogenous lipogenesis or its functions as a lipokine are under debate. Objective was to assess the predictive role of adipose triglycerides fatty acids in weight maintenance in participants of the DIOGENES dietary intervention study. After an 8-week low calorie diet (LCD) subjects with > 8 % weight loss were randomized to 5 ad libitum weight maintenance diets for 6 months: low protein (P)/low glycemic index (GI) (LP/LGI), low P/high GI (LP/HGI), high P/low GI (HP/LGI), high P/high GI (HP/HGI), and a control diet. Fatty acid composition in adipose tissue triglycerides was determined by gas chromatography in 195 subjects before the LCD (baseline), after LCD and weight maintenance. Weight change after the maintenance phase was positively correlated with baseline adipose palmitoleic (16:1n-7), myristoleic (14:1n-5) and trans-palmitoleic acid (16:1n-7t). Negative correlation was found with baseline oleic acid (18:1n-9). Lower baseline monounsaturated fatty acids (14:1n-5, 16:1n-7 and trans 16:1n-7) in adipose tissue triglycerides predict better weight maintenance. Lower oleic acid predicts lower weight decrease. These findings suggest a specific role of monounsaturated fatty acids in weight management and as weight change predictors.

• MeSH
• dospělí MeSH
• glykemický index MeSH
• hmotnostní úbytek fyziologie   MeSH
• kyselina olejová chemie   metabolismus   MeSH
• kyseliny mastné mononenasycené chemie   metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mastné kyseliny chemie   metabolismus   MeSH
• tělesná hmotnost MeSH
• triglyceridy analýza   metabolismus   MeSH
• tuková tkáň chemie   metabolismus   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 9-tetradecenoic acid MeSH Prohlížeč
• kyselina olejová MeSH
• kyseliny mastné mononenasycené MeSH
• mastné kyseliny MeSH
• palmitoleic acid MeSH Prohlížeč
• triglyceridy MeSH