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

Thyroid dysfunction is associated with several abnormalities in intermediary metabolism, including impairment of lipolytic response to catecholamines in subcutaneous abdominal adipose tissue (SCAAT). Atrial natriuretic peptide (ANP) is a powerful lipolytic peptide; however, the role of ANP-mediated lipolysis in thyroid disease has not been elucidated. The aim of this study was to investigate the role of thyroid hormones in the regulation of ANP-induced lipolysis as well as in the gene expression of hormone-sensitive lipase, phosphodiesterase 3B (PDE3B), uncoupling protein-2 (UCP2), natriuretic peptide receptor type A, and beta(2)-adrenergic receptor in SCAAT of hyperthyroid and hypothyroid patients. Gene expression in SCAAT was studied in 13 hypothyroid and 11 hyperthyroid age-matched women before and 2-4 mo after the normalization of their thyroid status. A microdialysis study was performed on a subset of nine hyperthyroid and 10 hypothyroid subjects. ANP- and isoprenaline-induced lipolyses were higher in hyperthyroid subjects, with no differences between the groups following treatment. Hormone-sensitive lipase gene expression was higher in hyperthyroid compared with hypothyroid subjects before treatment, whereas no difference was observed following treatment. No differences in gene expression of other genes were observed between the two groups. Following treatment, the gene expression of UCP2 decreased in hyperthyroid, whereas the expression of PDE3B decreased in hypothyroid subjects. We conclude that thyroid hormones regulate ANP- and isoprenaline-mediated lipolysis in human SCAAT in vivo. Increased lipolytic subcutaneous adipose tissue response in hyperthyroid patients may involve postreceptor signaling mechanisms.

• MeSH
• financování organizované MeSH
• Publikační typ
• klinické zkoušky kontrolované MeSH
• Geografické názvy
• atriální natriuretický faktor MeSH
• dospělí MeSH
• energetický metabolismus MeSH
• hypertyreóza MeSH
• hypotyreóza MeSH
• isoprenalin MeSH
• katecholaminy MeSH
• lidé středního věku MeSH
• lidé MeSH
• lipolýza MeSH
• podkožní břišní tuk MeSH
• regionální krevní průtok MeSH
• regulace genové exprese MeSH
• senioři MeSH
• tělesná hmotnost MeSH
• ženské pohlaví MeSH