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

0583338 - FGÚ 2025 RIV US eng J - Journal Article
Šiklová, M. - Šrámková, V. - Koc, M. - Krauzová, E. - Čížková, T. - Ondrůjová, B. - Wilhelm, M. - Varaliová, Z. - Kuda, Ondřej - Neubert, J. - Lambert, L. - Elkalaf, M. - Gojda, J. - Rossmeislová, L.
The role of adipogenic capacity and dysfunctional subcutaneous adipose tissue in the inheritance of type 2 diabetes mellitus: cross-sectional study.
Obesity. Roč. 32, č. 3 (2024), s. 547-559. ISSN 1930-7381. E-ISSN 1930-739X
R&D Projects: GA MŠMT(CZ) LX22NPO5104
Grant - others:AV ČR(CZ) LQ200111901
Program: Prémie Lumina quaeruntur
Institutional support: RVO:67985823
Keywords : insulin sensitivity * visceral fat * obesity * adipose tissue
OECD category: Endocrinology and metabolism (including diabetes, hormones)
Impact factor: 6.9, year: 2022
Method of publishing: Open access
https://doi.org/10.1002/oby.23969

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.
Permanent Link: https://hdl.handle.net/11104/0351313