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The role of adipogenic capacity and dysfunctional subcutaneous adipose tissue in the inheritance of type 2 diabetes mellitus: cross-sectional study

M. Šiklová, V. Šrámková, M. Koc, E. Krauzová, T. Čížková, B. Ondrůjová, M. Wilhelm, Z. Varaliová, O. Kuda, J. Neubert, L. Lambert, M. Elkalaf, J. Gojda, L. Rossmeislová

. 2024 ; 32 (3) : 547-559. [pub] 20240114

Jazyk angličtina Země Spojené státy americké

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/bmc24006914

Grantová podpora
NV19-01-00263 Agentura Pro Zdravotnický Výzkum České Republiky
LQ200111901 Akademie Věd České Republiky
LX22NPO5104 European Union - Next Generation EU
16-14048S Grantová Agentura České Republiky
260646/SVV/2023 Univerzita Karlova v Praze
COOPERATIO Univerzita Karlova v Praze
NV19-01-00263 Ministry of Health of the Czech Republic
LQ200111901 Czech Academy of Sciences
16-14048S Grant Agency of the Czech Republic
260646/SVV/2023 Charles University
COOPERATIO Charles University

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.

Citace poskytuje Crossref.org

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