Expression of lipogenic markers is decreased in subcutaneous adipose tissue and adipocytes of older women and is negativ
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ORIGINAL ARTICLE
Expression of lipogenic markers is decreased in subcutaneous adipose tissue and adipocytes of older women and is negatively linked to GDF15 expression Veronika Šrámková 1,2 & Michal Koc 1,2 & Eva Krauzová 1,2,3 & Jana Kračmerová 1,2 & Michaela Šiklová 1,2 & Moustafa Elkalaf 4 & Dominique Langin 2,5,6,7 & Vladimír Štich 1,2,3 & Lenka Rossmeislová 1,2 Received: 16 October 2018 / Accepted: 10 February 2019 # University of Navarra 2019
Abstract In aging, the capacity of subcutaneous adipose tissue (SAT) to store lipids decreases and this results in metabolically unfavorable fat redistribution. Triggers of this age-related SAT dysfunction may include cellular senescence or endoplasmic reticulum (ER) stress. Therefore, we compared lipogenic capacity of SAT between young and older women and investigated its relation to senescence and ER stress markers. Samples of SAT and corresponding SAT-derived primary preadipocytes were obtained from two groups of women differing in age (36 vs. 72 years, n = 15 each) but matched for fat mass. mRNA levels of selected genes (lipogenesis: ACACA, FASN, SCD1, DGAT2, ELOVL6; senescence: p16, p21, NOX4, GDF15; ER stress-ATF4, XBP1s, PERK, HSPA5, GADD34, HYOU1, CHOP, EDEM1, DNAJC3) were assessed by qPCR, protein levels of GDF15 by ELISA, and mitochondrial function by the Seahorse Analyzer. Compared to the young, SAT and in vitro differentiated adipocytes from older women exhibited reduced mRNA expression of lipogenic enzymes. Out of analyzed senescence and ER stress markers, the only gene, whose expression correlated negatively with the expression of lipogenic enzymes in both SAT and adipocytes, was GDF15, a marker of not only senescence but also mitochondrial dysfunction. In line with this, inhibition of mitochondrial ATP synthase in adipocytes strongly upregulated GDF15 while reduced expression of lipogenic enzymes. Moreover, adipocytes from older women had a tendency for diminished mitochondrial capacity. Thus, a reduced lipogenic capacity of adipocytes in aged SAT appears to be linked to mitochondrial dysfunction rather than to ER stress or accumulation of senescent cells. Keywords Subcutaneous adipose tissue . Lipogenesis . Aging . Senescence . Stress of endoplasmic reticulum . Mitochondrial dysfunction
Introduction Subcutaneous adipose tissue (SAT) is an organ specialized for the synthesis and metabolically safe storage of
lipids through process of lipogenesis and thus it is indispensable for the maintenance of whole-body energy homeostasis [24]. For lipogenesis, AT utilizes mainly dietary lipids (in a process referred to as reesterification
* Lenka Rossmeislová [email protected] 1
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Department of Pathophysiology, Third Faculty of Medicine, Charles University, Prague, Czech Republic
Department of Biochemistry, Cell and Molecular Biology, Third Faculty of Medicine, Charles University, Prague, Czech Republic
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Franco-Czech Laboratory for Clinical Research on Obesity, Third Faculty of Medicine, Prague, Czech Republic
INSERM, UMR1048, Institute
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