Since the 1950s, one of the goals of adipose tissue research has been to determine lipolytic and lipogenic activity as the primary metabolic pathways affecting adipocyte health and size and thus representing potential therapeutic targets for the treatment of obesity and associated diseases. Nowadays, there is a relatively large number of methods to measure the activity of these pathways and involved enzymes, but their applicability to different biological samples is variable. Here, we review the characteristics of mean lipogenic and lipolytic enzymes, their inhibitors, and available methodologies for assessing their activity, and comment on the advantages and disadvantages of these methodologies and their applicability in vivo, ex vivo, and in vitro, i.e., in cells, organs and their respective extracts, with the emphasis on adipocytes and adipose tissue.

• Klíčová slova
• acetyl-CoA carboxylase, activity measurement, adipose triglyceride lipase, fatty-acid synthase, hormone-sensitive lipase, inhibitor,
• MeSH
• lidé MeSH
• lipogeneze * MeSH
• lipolýza * MeSH
• obezita metabolismus   MeSH
• tuková tkáň metabolismus   MeSH
• tukové buňky metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy 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

Objective: Anti-lipolytic drugs and exercise are enhancers of growth hormone (GH) secretion. Decreased circulating free fatty acids (FFA) have been proposed to exert ghrelin-GH feedback loop after administration of an anti-lipolytic longer-acting analog of nicotinic acid, Acipimox (OLB, 5-Methylpyrazine-2-carboxylic acid 4-oxide, molecular weight of 154.1 Da). OLB administration strongly suppresses plasma FFA during exercise. Neuroendocrine perturbations of the adipose tissue (AT), gut, and brain peptides may be involved in the etiopathogenesis of eating disorders including bulimia nervosa (BN) and anorexia nervosa. BN is characterized by binge eating, self-induced vomiting or excessive exercise. Approach: To test the hypothesis that treatment with OLB together with exercise vs. exercise alone would induce feedback action of GH, pancreatic polypeptide (PP), peptide tyrosine tyrosine (PYY), and leptin on ghrelin in Czech women with BN and in healthy-weight Czech women (HW). The lipolysis rate (as glycerol release) in subcutaneous abdominal AT was assessed with microdialysis. At an academic medical center, 12 BN and 12 HW (the control group) were randomized to OLB 500 mg 1 h before a single exercise bout (45 min, 2 W/kg of lean body mass [LBM]) once a week vs. identical placebo over a total of 2 weeks. Blood plasma concentrations of GH, PP, PYY, leptin, ghrelin, FFA, glycerol, and concentrations of AT interstitial glycerol were estimated during the test by RIA utilizing 125I-labeled tracer, the electrochemiluminescence technique (ECLIA) or colorimetric kits. Results: OLB administration together with short-term exercise significantly increased plasma GH (P < 0.0001), PP (P < 0.0001), PYY, and leptin concentrations and significantly decreased plasma ghrelin (P < 0.01) concentrations in both groups, whereas short-term exercise with placebo resulted in plasma ghrelin (P < 0.05) decrease exclusively in BN. OLB administration together with short-term exercise significantly lowered local subcutaneous abdominal AT interstitial glycerol (P < 0.0001) to a greater extent in BN. Conclusion: OLB-induced suppression of plasma ghrelin concentrations together with short-term exercise and after the post-exercise recovering phase suggests a potential negative co-feedback of GH, PP, PYY, and leptin on ghrelin secretion to a greater extent in BN. Simultaneously, the exercise-induced elevation in AT interstitial glycerol leading to a higher inhibition of peripheral lipolysis by OLB in BN. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT03338387.

• Klíčová slova
• eating disorders, exercise, ghrelin, growth hormone, human adipose tissue, microdialysis, olbetam, pancreatic polypeptide family,
• Publikační typ
• časopisecké články MeSH

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

Contribution of individual adiponectin isoforms to lipolysis regulation remains unknown. We investigated the impact of full-length, trimeric and globular adiponectin isoforms on spontaneous lipolysis in subcutaneous abdominal (SCAAT) and visceral adipose tissues (VAT) of obese and non-obese subjects. Furthermore, we explored the role of AMPK (5'-AMP-activated protein kinase) in adiponectin-dependent lipolysis regulation and expression of adiponectin receptors type 1 and 2 (AdipoR1 and AdipoR2) in SCAAT and VAT. Primary adipocytes isolated from SCAAT and VAT of obese and non-obese women were incubated with 20 µg/ml of: A) full-length adiponectin (physiological mixture of all adiponectin isoforms), B) trimeric adiponectin isoform or C) globular adiponectin isoform. Glycerol released into media was used as a marker of lipolysis. While full-length adiponectin inhibited lipolysis by 22% in non-obese SCAAT, globular isoform inhibited lipolysis by 27% in obese SCAAT. No effect of either isoform was detected in non-obese VAT, however trimeric isoform inhibited lipolysis by 21% in obese VAT (all p<0.05). Trimeric isoform induced Thr172 p-AMPK in differentiated preadipocytes from a non-obese donor, while globular isoform induced Ser79 p-ACC by 32% (p<0.05) and Ser565 p-HSL by 52% (p = 0.08) in differentiated preadipocytes from an obese donor. AdipoR2 expression was 17% and 37% higher than AdipoR1 in SCAAT of obese and non-obese groups and by 23% higher in VAT of obese subjects (all p<0.05). In conclusion, the anti-lipolytic effect of adiponectin isoforms is modified with obesity: while full-length adiponectin exerts anti-lipolytic action in non-obese SCAAT, globular and trimeric isoforms show anti-lipolytic activity in obese SCAAT and VAT, respectively.

• MeSH
• adiponektin krev   chemie   metabolismus   MeSH
• aminoimidazolkarboxamid analogy a deriváty   farmakologie   MeSH
• dospělí MeSH
• exprese genu účinky léků   MeSH
• hypoglykemika farmakologie   MeSH
• kultivované buňky MeSH
• kvantitativní polymerázová řetězová reakce MeSH
• lidé středního věku MeSH
• lidé MeSH
• lipolýza účinky léků   MeSH
• multimerizace proteinu účinky léků   MeSH
• nitrobřišní tuk cytologie   MeSH
• obezita patologie   MeSH
• podkožní tuk cytologie   MeSH
• protein - isoformy krev   chemie   metabolismus   MeSH
• proteinkinasy aktivované AMP metabolismus   MeSH
• receptory adiponektinu genetika   metabolismus   MeSH
• ribonukleotidy farmakologie   MeSH
• tukové buňky cytologie   účinky léků   metabolismus   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• adiponektin MeSH
• ADIPOR1 protein, human MeSH Prohlížeč
• ADIPOR2 protein, human MeSH Prohlížeč
• AICA ribonucleotide MeSH Prohlížeč
• aminoimidazolkarboxamid MeSH
• hypoglykemika MeSH
• protein - isoformy MeSH
• proteinkinasy aktivované AMP MeSH
• receptory adiponektinu MeSH
• ribonukleotidy MeSH

BACKGROUND: Neuropeptide Y (NPY) is an important central orexigenic hormone predominantly produced by the hypothalamus, and recently found to be secreted in adipose tissue (AT). Acipimox (Aci) inhibits lipolysis in AT and reduces plasma glycerol and free fatty acid (FFA) levels. Exercise and Aci are enhancers of growth hormone (GH) and NPY secretion and exercise may alter leptin levels. We expect to find abnormal neuropeptidergic response in plasma and AT in patients with bulimia nervosa (BN). We hypothesize that Aci influences these peptides via a FFA-independent mechanism and that Aci inhibits lipolysis through a cyclic adenosine monophosphate (cAMP)-dependent pathway. Dysregulations of the AT-brain axis peptides might be involved in binge eating as is the case in BN. METHODS: The objective of this study was to determine the responses of plasma NPY, GH, leptin, FFA and glycerol levels to exercise in BN patients and healthy women (C) given the anti-lipolytic drug Aci or placebo. The secondary objective of this study was to compare the responses of extracellular glycerol levels and plasma glycerol levels to exercise alone or together with Aci administration in BN patients and C women. Extracellular glycerol was measured in vivo in subcutaneous (sc) abdominal AT using microdialysis. Eight BN and eight C women were recruited for this single-blind, randomized study. Aci or placebo was given 1 hour before the exercise (45 min, 2 W/kg of lean body mass [LBM]). NPY, GH, leptin, FFA, glycerol plasma and AT glycerol levels were measured using commercial kits. RESULTS: The primary outcome of this study was that the exercise with Aci administration resulted in plasma NPY and GH increase (after a 45-minute exercise) and leptin (after a 90-minute post-exercise recovering phase) increased more in BN patients. The secondary outcomes of this study were that the exercise with Aci administration induced a higher decrease of extracellular glycerol in BN patients compared to the C group, while the exercise induced a higher increase of glycerol concentrations in sc abdominal AT of BN patients. Plasma glycerol levels decreased more in BN patients and plasma FFA levels were depressed in both groups after the exercise with Aci administration. The exercise induced similar increases in plasma NPY, GH, FFA and glycerol levels, and a similar decrease in the plasma leptin level in both groups. CONCLUSIONS: We confirm the results of a single-blind, randomized, microdialysis study, i.e. that the Aci-induced elevation in plasma NPY and GH levels during the exercise is higher in BN patients and that Aci increased plasma leptin levels in the post-exercise recovering phase (90-minute) more in BN patients. The post-exercise rise (45-minute) in AT glycerol is much more attenuated by acute Aci treatment in BN patients. Simultaneously, we found facilitated turnover of plasma glycerol after the exercise together with Aci administration in BN. Our results support the hypotheses that Aci exerts an effect on the FFA-independent and cAMP-dependent mechanism. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12611000955910.

• Publikační typ
• časopisecké články MeSH