BACKGROUND: Adipocytes are cells specialized for storage of neutral lipids. This storage capacity is dependent on lipogenesis and is diminished in obesity. The reason for the decline in lipogenic activity of adipocytes in obesity remains unknown. Recent data show that lipogenesis in liver is regulated by pathways initiated by endoplasmic reticulum stress (ERS). Thus, we aimed at investigating the effect of ERS on lipogenesis in adipose cells. METHODS: Preadipocytes were isolated from subcutaneous abdominal adipose tissue from obese volunteers and in vitro differentiated into adipocytes. ERS was induced pharmacologically by thapsigargin (TG) or tunicamycin (TM). Activation of Unfolded Protein Response pathway (UPR) was monitored on the level of eIF2α phosphorylation and mRNA expression of downstream targets of UPR sensors. Adipogenic and lipogenic capacity was evaluated by Oil Red O staining, measurement of incorporation of radio-labelled glucose or acetic acid into lipids and mRNA analysis of adipogenic/lipogenic markers. RESULTS: Exposition of adipocytes to high doses of TG (100 nM) and TM (1 μg/ml) for 1-24 h enhanced expression of several UPR markers (HSPA5, EDEM1, ATF4, XBP1s) and phosphorylation of eIF2α. This acute ERS substantially inhibited expression of lipogenic genes (DGAT2, FASN, SCD1) and glucose incorporation into lipids. Moreover, chronic exposure of preadipocytes to low dose of TG (2.5 nM) during the early phases of adipogenic conversion of preadipocytes impaired both, lipogenesis and adipogenesis. On the other hand, chronic low ERS had no apparent effect on lipogenesis in mature adipocytes. CONCLUSIONS: Acute ERS weakened a capacity of mature adipocytes to store lipids and chronic ERS diminished adipogenic potential of preadipocytes.

Franco Czech Laboratory for Clinical Research on Obesity 3rd Faculty of Medicine Prague Czech Republic; Department of Sport Medicine 3rd Faculty of Medicine Charles University Prague CZ 100 00 Czech Republic

Franco Czech Laboratory for Clinical Research on Obesity 3rd Faculty of Medicine Prague Czech Republic; Inserm UMR1048 Obesity Research Laboratory Institute of Metabolic and Cardiovascular Diseases 31432 Toulouse Cedex 4 France

Franco Czech Laboratory for Clinical Research on Obesity 3rd Faculty of Medicine Prague Czech Republic; Inserm UMR1048 Obesity Research Laboratory Institute of Metabolic and Cardiovascular Diseases 31432 Toulouse Cedex 4 France; University of Toulouse UMR1048 Paul Sabatier University 31432 Toulouse Cedex 4 France; Toulouse University Hospitals Department of Clinical Biochemistry 31059 Toulouse Cedex 9 France

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Expression of lipogenic markers is decreased in subcutaneous adipose tissue and adipocytes of older women and is negatively linked to GDF15 expression