PMID- 38221680 OWN - NLM STAT- MEDLINE DCOM- 20240228 LR - 20240228 IS - 1930-739X (Electronic) IS - 1930-7381 (Linking) VI - 32 IP - 3 DP - 2024 Mar TI - The role of adipogenic capacity and dysfunctional subcutaneous adipose tissue in the inheritance of type 2 diabetes mellitus: cross-sectional study. PG - 547-559 LID - 10.1002/oby.23969 [doi] AB - 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. CI - (c) 2024 The Authors. Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society. FAU - Siklova, Michaela AU - Siklova M AUID- ORCID: 0000-0003-0489-1069 AD - Department of Pathophysiology, Center for Research on Nutrition, Metabolism and Diabetes, Third Faculty of Medicine, Charles University, Prague, Czech Republic. AD - Franco-Czech Laboratory for Clinical Research on Obesity, Third Faculty of Medicine, Charles University, Prague, Czech Republic. FAU - Sramkova, Veronika AU - Sramkova V AD - Department of Pathophysiology, Center for Research on Nutrition, Metabolism and Diabetes, Third Faculty of Medicine, Charles University, Prague, Czech Republic. AD - Franco-Czech Laboratory for Clinical Research on Obesity, Third Faculty of Medicine, Charles University, Prague, Czech Republic. FAU - Koc, Michal AU - Koc M AD - Department of Pathophysiology, Center for Research on Nutrition, Metabolism and Diabetes, Third Faculty of Medicine, Charles University, Prague, Czech Republic. AD - Franco-Czech Laboratory for Clinical Research on Obesity, Third Faculty of Medicine, Charles University, Prague, Czech Republic. FAU - Krauzova, Eva AU - Krauzova E AD - Department of Pathophysiology, Center for Research on Nutrition, Metabolism and Diabetes, Third Faculty of Medicine, Charles University, Prague, Czech Republic. AD - Franco-Czech Laboratory for Clinical Research on Obesity, Third Faculty of Medicine, Charles University, Prague, Czech Republic. AD - Department of Internal Medicine, Kralovske Vinohrady University Hospital, Prague, Czech Republic. FAU - Cizkova, Terezie AU - Cizkova T AUID- ORCID: 0000-0001-7565-2984 AD - Department of Pathophysiology, Center for Research on Nutrition, Metabolism and Diabetes, Third Faculty of Medicine, Charles University, Prague, Czech Republic. FAU - Ondrujova, Barbora AU - Ondrujova B AD - Department of Pathophysiology, Center for Research on Nutrition, Metabolism and Diabetes, Third Faculty of Medicine, Charles University, Prague, Czech Republic. FAU - Wilhelm, Marek AU - Wilhelm M AD - Department of Pathophysiology, Center for Research on Nutrition, Metabolism and Diabetes, Third Faculty of Medicine, Charles University, Prague, Czech Republic. FAU - Varaliova, Zuzana AU - Varaliova Z AD - Department of Pathophysiology, Center for Research on Nutrition, Metabolism and Diabetes, Third Faculty of Medicine, Charles University, Prague, Czech Republic. FAU - Kuda, Ondrej AU - Kuda O AD - Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic. FAU - Neubert, Jana AU - Neubert J AD - Department of Pathophysiology, Center for Research on Nutrition, Metabolism and Diabetes, Third Faculty of Medicine, Charles University, Prague, Czech Republic. FAU - Lambert, Lukas AU - Lambert L AD - Department of Radiology, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic. FAU - Elkalaf, Moustafa AU - Elkalaf M AD - Department of Pathophysiology, Center for Research on Nutrition, Metabolism and Diabetes, Third Faculty of Medicine, Charles University, Prague, Czech Republic. FAU - Gojda, Jan AU - Gojda J AD - Franco-Czech Laboratory for Clinical Research on Obesity, Third Faculty of Medicine, Charles University, Prague, Czech Republic. AD - Department of Internal Medicine, Kralovske Vinohrady University Hospital, Prague, Czech Republic. FAU - Rossmeislova, Lenka AU - Rossmeislova L AD - Department of Pathophysiology, Center for Research on Nutrition, Metabolism and Diabetes, Third Faculty of Medicine, Charles University, Prague, Czech Republic. AD - Franco-Czech Laboratory for Clinical Research on Obesity, Third Faculty of Medicine, Charles University, Prague, Czech Republic. LA - eng GR - NV19-01-00263/Agentura Pro Zdravotnicky Vyzkum Ceske Republiky/ GR - LQ200111901/Akademie Ved Ceske Republiky/ GR - LX22NPO5104/European Union - Next Generation EU/ GR - 16-14048S/Grantova Agentura Ceske Republiky/ GR - 260646/SVV/2023/Univerzita Karlova v Praze/ GR - COOPERATIO/Univerzita Karlova v Praze/ GR - NV19-01-00263/Ministry of Health of the Czech Republic/ GR - LQ200111901/Czech Academy of Sciences/ GR - 16-14048S/Grant Agency of the Czech Republic/ GR - 260646/SVV/2023/Charles University/ GR - COOPERATIO/Charles University/ PT - Journal Article DEP - 20240114 PL - United States TA - Obesity (Silver Spring) JT - Obesity (Silver Spring, Md.) JID - 101264860 RN - 0 (Triglycerides) RN - 0 (Fatty Acids, Unsaturated) RN - 0 (RNA, Messenger) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/genetics/metabolism MH - Cross-Sectional Studies MH - Subcutaneous Fat/metabolism MH - *Insulin Resistance/genetics MH - Obesity/genetics/metabolism MH - Intra-Abdominal Fat/metabolism MH - Triglycerides/metabolism MH - Fatty Acids, Unsaturated/metabolism MH - RNA, Messenger/metabolism MH - Adipose Tissue/metabolism EDAT- 2024/01/15 06:42 MHDA- 2024/02/28 06:44 CRDT- 2024/01/15 00:23 PHST- 2023/10/13 00:00 [revised] PHST- 2023/04/17 00:00 [received] PHST- 2023/11/09 00:00 [accepted] PHST- 2024/02/28 06:44 [medline] PHST- 2024/01/15 06:42 [pubmed] PHST- 2024/01/15 00:23 [entrez] AID - 10.1002/oby.23969 [doi] PST - ppublish SO - Obesity (Silver Spring). 2024 Mar;32(3):547-559. doi: 10.1002/oby.23969. Epub 2024 Jan 14.