OBJECTIVE: This study tested the hypothesis that limited subcutaneous adipose tissue (SAT) expansion represents a primary predisposition to the development of type 2 diabetes mellitus (T2DM), independent of obesity, and identified novel markers of SAT dysfunction in the inheritance of T2DM. METHODS: First-degree relatives (FDR) of T2DM patients (n = 19) and control individuals (n = 19) without obesity (fat mass < 25%) were cross-sectionally compared. Body composition (bioimpedance, computed tomography) and insulin sensitivity (IS; oral glucose tolerance test, clamp) were measured. SAT obtained by needle biopsy was used to analyze adipocyte size, lipidome, mRNA expression, and inflammatory markers. Primary cultures of adipose precursors were analyzed for adipogenic capacity and metabolism. RESULTS: Compared with control individuals, FDR individuals had lower IS and a higher amount of visceral fat. However, SAT-derived adipose precursors did not differ in their ability to proliferate and differentiate or in metabolic parameters (lipolysis, mitochondrial oxidation). In SAT of FDR individuals, lipidomic and mRNA expression analysis revealed accumulation of triglycerides containing polyunsaturated fatty acids and increased mRNA expression of lysyl oxidase (LOX). These parameters correlated with IS, visceral fat accumulation, and mRNA expression of inflammatory and cellular stress genes. CONCLUSIONS: The intrinsic adipogenic potential of SAT is not affected by a family history of T2DM. However, alterations in LOX mRNA and polyunsaturated fatty acids in triacylglycerols are likely related to the risk of developing T2DM independent of obesity.

• MeSH
• diabetes mellitus 2. typu * genetika   metabolismus   MeSH
• inzulinová rezistence * genetika   MeSH
• lidé MeSH
• messenger RNA metabolismus   MeSH
• nenasycené mastné kyseliny metabolismus   MeSH
• nitrobřišní tuk metabolismus   MeSH
• obezita genetika   metabolismus   MeSH
• podkožní tuk metabolismus   MeSH
• průřezové studie MeSH
• triglyceridy metabolismus   MeSH
• tuková tkáň metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Exercise improves the insulin sensitivity of glucose uptake in skeletal muscle. Due to that, exercise has become a cornerstone treatment for type 2 diabetes mellitus (T2DM). The mechanisms by which exercise improves skeletal muscle insulin sensitivity are, however, incompletely understood. We conducted a systematic review to identify all genes whose gain or loss of function alters skeletal muscle glucose uptake. We subsequently cross-referenced these genes with recently generated data sets on exercise-induced gene expression and signaling. Our search revealed 176 muscle glucose-uptake genes, meaning that their genetic manipulation altered glucose uptake in skeletal muscle. Notably, exercise regulates the expression or phosphorylation of more than 50% of the glucose-uptake genes or their protein products. This included many genes that previously have not been associated with exercise-induced insulin sensitivity. Interestingly, endurance and resistance exercise triggered some common but mostly unique changes in expression and phosphorylation of glucose-uptake genes or their protein products. Collectively, our work provides a resource of potentially new molecular effectors that play a role in the incompletely understood regulation of muscle insulin sensitivity by exercise.

• MeSH
• diabetes mellitus 2. typu * genetika   metabolismus   MeSH
• fyzická vytrvalost genetika   MeSH
• inzulinová rezistence genetika   MeSH
• kosterní svaly metabolismus   MeSH
• krevní glukóza * genetika   metabolismus   MeSH
• lidé MeSH
• odporový trénink * MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

Background: The MTNR1B gene encodes a receptor for melatonin, a hormone regulating biorhythms. Disruptions in biorhythms contribute to the development of type 2 diabetes mellitus (T2DM). Genetic studies suggest that variability in the MTNR1B gene affects T2DM development. Our aim was to compare the distribution of the genetic variant rs10830963 between persons differing in glucose tolerance in a sample of the Czech population (N=1206). We also evaluated possible associations of the polymorphism with insulin sensitivity, beta cell function, with the shape of glucose, insulin and C-peptide trajectories measured 7 times during a 3-hour oral glucose tolerance test (OGTT) and with glucagon response. In a subgroup of 268 volunteers we also evaluated sleep patterns and biorhythm. Results: 13 persons were diagnosed with T2DM, 119 had impaired fasting blood glucose (IFG) and/or impaired glucose tolerance (IGT). 1074 participants showed normal results and formed a control group. A higher frequency of minor allele G was found in the IFG/IGT group in comparison with controls. The GG constellation was present in 23% of diabetics, in 17% of IFG/IGT probands and in 11% of controls. Compared to CC and CG genotypes, GG homozygotes showed higher stimulated glycemia levels during the OGTT. Homozygous as well as heterozygous carriers of the G allele showed lower very early phase of insulin and C-peptide secretion with unchanged insulin sensitivity. These differences remained significant after excluding diabetics and the IFG/IGT group from the analysis. No associations of the genotype with the shape of OGTT-based trajectories, with glucagon or with chronobiological patterns were observed. However, the shape of the trajectories differed significantly between men and women. Conclusion: In a representative sample of the Czech population, the G allele of the rs10830963 polymorphism is associated with impaired early phase of beta cell function, and this is evident even in healthy individuals.

• MeSH
• C-peptid MeSH
• diabetes mellitus 2. typu * epidemiologie   genetika   MeSH
• glukagon MeSH
• glukosa MeSH
• inzulin MeSH
• inzulinová rezistence * genetika   MeSH
• kinetika MeSH
• krevní glukóza MeSH
• lidé MeSH
• porucha glukózové tolerance * epidemiologie   genetika   MeSH
• prediabetes * MeSH
• receptor melatoninový MT2 * genetika   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

The microbiota-harboring human gut is an exquisitely active ecosystem that has evolved in a constant symbiosis with the human host. It produces numerous compounds depending on its metabolic capacity and substrates availability. Diet is the major source of the substrates that are metabolized to end-products, further serving as signal molecules in the microbiota-host cross-talk. Among these signal molecules, branched-chain amino acids (BCAAs) has gained significant scientific attention. BCAAs are abundant in animal-based dietary sources; they are both produced and degraded by gut microbiota and the host circulating levels are associated with the risk of type 2 diabetes. This review aims to summarize the current knowledge on the complex relationship between gut microbiota and its functional capacity to handle BCAAs as well as the host BCAA metabolism in insulin resistance development. Targeting gut microbiota BCAA metabolism with a dietary modulation could represent a promising approach in the prevention and treatment of insulin resistance related states, such as obesity and diabetes.

• MeSH
• diabetes mellitus 2. typu krev   genetika   MeSH
• inzulinová rezistence genetika   MeSH
• krevní glukóza genetika   MeSH
• lidé MeSH
• obezita krev   genetika   MeSH
• střevní mikroflóra genetika   MeSH
• symbióza genetika   MeSH
• větvené aminokyseliny krev   genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

G-protein-coupled receptor GPR10 is expressed in brain areas regulating energy metabolism. In this study, the effects of GPR10 gene deficiency on energy homeostasis in mice of both sexes fed either standard chow or a high-fat diet (HFD) were studied, with a focus on neuronal activation of PrRP neurons, and adipose tissue and liver metabolism. GPR10 deficiency in males upregulated the phasic and tonic activity of PrRP neurons in the nucleus of the solitary tract. GPR10 knockout (KO) males on a standard diet displayed a higher body weight than their wild-type (WT) littermates due to an increase in adipose tissue mass; however, HFD feeding did not cause weight differences between genotypes. Expression of lipogenesis genes was suppressed in the subcutaneous adipose tissue of GPR10 KO males. In contrast, GPR10 KO females did not differ in body weight from their WT controls, but showed elevated expression of lipid metabolism genes in the liver and subcutaneous adipose tissue compared to WT controls. An attenuated non-esterified fatty acids change after glucose load compared to WT controls suggested a defect in insulin-mediated suppression of lipolysis in GPR10 KO females. Indirect calorimetry did not reveal any differences in energy expenditure among groups. In conclusion, deletion of GPR10 gene resulted in changes in lipid metabolism in mice of both sexes, however in different extent. An increase in adipose tissue mass observed in only GPR10 KO males may have been prevented in GPR10 KO females owing to a compensatory increase in the expression of metabolic genes.

• MeSH
• energetický metabolismus genetika   MeSH
• homeostáza genetika   MeSH
• hormon uvolňující prolaktin metabolismus   MeSH
• inzulinová rezistence genetika   MeSH
• metabolismus lipidů genetika   MeSH
• myši inbrední C57BL MeSH
• myši knockoutované MeSH
• myši MeSH
• obezita genetika   MeSH
• receptory spřažené s G-proteiny genetika   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: The classical functions of the skeleton encompass locomotion, protection and mineral homeostasis. However, cell-specific gene deletions in the mouse and human genetic studies have identified the skeleton as a key endocrine regulator of metabolism. The bone-specific phosphatase, Phosphatase, Orphan 1 (PHOSPHO1), which is indispensable for bone mineralisation, has been recently implicated in the regulation of energy metabolism in humans, but its role in systemic metabolism remains unclear. Here, we probe the mechanism underlying metabolic regulation by analysing Phospho1 mutant mice. RESULTS: Phospho1-/- mice exhibited improved basal glucose homeostasis and resisted high-fat-diet-induced weight gain and diabetes. The metabolic protection in Phospho1-/- mice was manifested in the absence of altered levels of osteocalcin. Osteoblasts isolated from Phospho1-/- mice were enriched for genes associated with energy metabolism and diabetes; Phospho1 both directly and indirectly interacted with genes associated with glucose transport and insulin receptor signalling. Canonical thermogenesis via brown adipose tissue did not underlie the metabolic protection observed in adult Phospho1-/- mice. However, the decreased serum choline levels in Phospho1-/- mice were normalised by feeding a 2% choline rich diet resulting in a normalisation in insulin sensitivity and fat mass. CONCLUSION: We show that mice lacking the bone mineralisation enzyme PHOSPHO1 exhibit improved basal glucose homeostasis and resist high-fat-diet-induced weight gain and diabetes. This study identifies PHOSPHO1 as a potential bone-derived therapeutic target for the treatment of obesity and diabetes.

• MeSH
• cholin metabolismus   MeSH
• energetický metabolismus * MeSH
• fosfatasy genetika   metabolismus   MeSH
• glukosa metabolismus   MeSH
• homeostáza MeSH
• inzulinová rezistence genetika   MeSH
• myši MeSH
• obezita genetika   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

Osteopontin (OPN) is a multifaceted matricellular protein, with well-recognized roles in both the physiological and pathological processes in the body. OPN is expressed in the main organs and cell types, in which it induces different biological actions. During physiological conditioning, OPN acts as both an intracellular protein and soluble excreted cytokine, regulating tissue remodeling and immune-infiltrate in adipose tissue the heart and the kidney. In contrast, the increased expression of OPN has been correlated with the severity of the cardiovascular and renal outcomes associated with obesity. Indeed, OPN expression is at the "cross roads" of visceral fat extension, cardiovascular diseases (CVDs) and renal disorders, in which OPN orchestrates the molecular interactions, leading to chronic low-grade inflammation. The common factor associated with OPN overexpression in adipose, cardiac and renal tissues seems attributable to the concomitant increase in visceral fat size and the increase in infiltrated OPN+ macrophages. This review underlines the current knowledge on the molecular interactions between obesity and the cardiac-renal disorders ruled by OPN.

• MeSH
• inzulinová rezistence genetika   MeSH
• ledviny metabolismus   patologie   MeSH
• lidé MeSH
• myokard metabolismus   patologie   MeSH
• nemoci ledvin genetika   metabolismus   patologie   MeSH
• nemoci srdce genetika   metabolismus   patologie   MeSH
• nitrobřišní tuk metabolismus   MeSH
• obezita genetika   metabolismus   patologie   MeSH
• osteopontin genetika   metabolismus   MeSH
• tuková tkáň metabolismus   MeSH
• zánět genetika   patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Elevated plasma concentration of apolipoprotein B-48 (apoB-48) is an independent risk factor of cardiovascular disease. Stearoyl-CoA desaturase-1 (SCD1) is a rate-limiting lipogenic enzyme and a key regulator of fuel metabolism. The aim of this study was to analyse associations between clinical, biochemical, and genetic factors and different apoB-48 levels in subjects at increased cardiometabolic risk. We examined 220 subjects exhibiting at least one metabolic syndrome (MetS) component. In conjunction with basic clinical, anthropometric and laboratory measurements, we analysed various polymorphisms of stearoyl-CoA desaturase-1 (SCD1). Subjects were divided into two groups according to the median apoB-48 level: (1) high apoB-48 (≥ 7.9 mg/l, N = 112) and (2) low apoB-48 (< 7.9 mg/l, N = 108). Neither group differed significantly in anthropometric measures. High plasma apoB-48 levels were associated with increased systolic blood pressure (+3 %; P < 0.05), MetS prevalence (59.8 vs. 32.4 %; P < 0.001), small-dense LDL frequency (46.4 vs. 20.4 %; P < 0.001), triglycerides (+97 %; P < 0.001), non-HDLcholesterol (+27 %; P < 0.001), and lower concentrations of HDL-cholesterol (-11 %; P < 0.01). This group was further characterized by a higher HOMA-IR index (+54 %; P < 0.001) and increased concentrations of conjugated dienes (+11 %; P < 0.001) and oxidatively modified LDL (+ 38 %; P < 0.05). Lower frequencies of SCD1 minor genotypes (rs2167444, rs508384, P < 0.05) were observed in subjects with elevated plasma concentrations of apoB-48. Elevated plasma concentrations of apoB-48 are associated with an adverse lipid profile, higher systolic blood pressure, insulin resistance, and oxidative stress. Lower proportions of minor SCD1 genotypes (rs2167444, rs508384) implicate the role of genetic factors in the pathogenesis of elevated levels of apoB-48.

• MeSH
• apolipoprotein B-48 krev   metabolismus   MeSH
• dospělí MeSH
• genotyp MeSH
• inzulinová rezistence genetika   MeSH
• jednonukleotidový polymorfismus genetika   MeSH
• kardiovaskulární nemoci krev   genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• oxidační stres genetika   fyziologie   MeSH
• rizikové faktory MeSH
• senioři MeSH
• stearyl-CoA-desaturasa genetika   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

INTRODUCTION: To reduce the risk of insulin resistance in obesity in children with lactase gene genotypes, we studied the factors that stimulate the chronic inflammatory process. MATERIAL AND METHODS: 109 children 6-18 years of age were investigated. The main group (n = 56) was presented by children with signs of insulin-resistant obesity according to the criteria of the European Society of Endocrinology and the Pediatric Endocrine Society. The control group (n = 53) included obese children without insulin resistance. A comprehensive clinical examination, food diary analysis, genotyping of the lactase gene by means of the polymerase chain reaction, the Immunochemical Test Method with Electrochemiluminescent Detection of basal insulinemia, Hydrogen breath test with lactose load, sequential analysis, ROC analysis were carried out. RESULTS: Clinical manifestations of lactose maldigestion in a child increased the risk of possible insulin resistance (prognostic coefficient (PC +2.6), as well as the presence of the lactase C/C 13910 gene genotype (PC +5.8) did. The genotype C/T 13910 in children had a protective effect on the risk of obesity (PC -2.9). The lowest risk of insulin-resistant obesity in observed among children with the genotype T/T 13910 (PC -12). CONCLUSION: The presence of the C/C 13910 genotype of the lactase gene is the main factor formation of insulin resistance in children's obesity. What is known? The genotype C/C 13910 of the lactase gene as a risk factor for the chronic inflammatory process in the body. What is New? Genotype C/C 13910 of the lactase gene as a risk factor for insulin-resistant obesity in children.

• MeSH
• dítě MeSH
• fenotyp MeSH
• genetická predispozice k nemoci * MeSH
• genetické markery MeSH
• genotyp * MeSH
• inzulinová rezistence genetika   MeSH
• jednonukleotidový polymorfismus * MeSH
• laktasa genetika   MeSH
• lidé MeSH
• logistické modely MeSH
• mladiství MeSH
• obezita dětí a dospívajících genetika   MeSH
• rizikové faktory MeSH
• ROC křivka MeSH
• studie případů a kontrol MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Context: Insulin resistance (IR) and obesity differ among ethnic groups in Singapore, with the Malays more obese yet less IR than Asian-Indians. However, the molecular basis underlying these differences is not clear. Objective: As the skeletal muscle (SM) is metabolically relevant to IR, we investigated molecular pathways in SM that are associated with ethnic differences in IR, obesity, and related traits. Design, Setting, and Main Outcome Measures: We integrated transcriptomic, genomic, and phenotypic analyses in 156 healthy subjects representing three major ethnicities in the Singapore Adult Metabolism Study. Patients: This study contains Chinese (n = 63), Malay (n = 51), and Asian-Indian (n = 42) men, aged 21 to 40 years, without systemic diseases. Results: We found remarkable diversity in the SM transcriptome among the three ethnicities, with >8000 differentially expressed genes (40% of all genes expressed in SM). Comparison with blood transcriptome from a separate Singaporean cohort showed that >95% of SM expression differences among ethnicities were unique to SM. We identified a network of 46 genes that were specifically downregulated in Malays, suggesting dysregulation of components of cellular respiration in SM of Malay individuals. We also report 28 differentially expressed gene clusters, four of which were also enriched for genes that were found in genome-wide association studies of metabolic traits and disease and correlated with variation in IR, obesity, and related traits. Conclusion: We identified extensive gene-expression changes in SM among the three Singaporean ethnicities and report specific genes and molecular pathways that might underpin and explain the differences in IR among these ethnic groups.

• MeSH
• celogenomová asociační studie MeSH
• dospělí MeSH
• etnicita genetika   MeSH
• index tělesné hmotnosti MeSH
• inzulinová rezistence etnologie   genetika   MeSH
• kohortové studie MeSH
• kosterní svaly metabolismus   MeSH
• lidé MeSH
• mladý dospělý MeSH
• signální transdukce genetika   MeSH
• stanovení celkové genové exprese MeSH
• transkriptom * MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Geografické názvy
• Singapur MeSH