PMID- 25813485 OWN - NLM STAT- MEDLINE DCOM- 20150821 LR - 20211203 IS - 1090-2104 (Electronic) IS - 0006-291X (Linking) VI - 460 IP - 3 DP - 2015 May 8 TI - Stress of endoplasmic reticulum modulates differentiation and lipogenesis of human adipocytes. PG - 684-90 LID - S0006-291X(15)00546-X [pii] LID - 10.1016/j.bbrc.2015.03.090 [doi] AB - 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 eIF2alpha 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 mug/ml) for 1-24 h enhanced expression of several UPR markers (HSPA5, EDEM1, ATF4, XBP1s) and phosphorylation of eIF2alpha. 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. CI - Copyright (c) 2015 Elsevier Inc. All rights reserved. FAU - Koc, Michal AU - Koc M AD - Franco-Czech Laboratory for Clinical Research on Obesity, Third Faculty of Medicine, Prague, Czech Republic; Department of Sport Medicine, Third Faculty of Medicine, Charles University in Prague, CZ-100 00, Czech Republic. FAU - Mayerova, Veronika AU - Mayerova V AD - Franco-Czech Laboratory for Clinical Research on Obesity, Third Faculty of Medicine, Prague, Czech Republic; Department of Sport Medicine, Third Faculty of Medicine, Charles University in Prague, CZ-100 00, Czech Republic. FAU - Kracmerova, Jana AU - Kracmerova J AD - Franco-Czech Laboratory for Clinical Research on Obesity, Third Faculty of Medicine, Prague, Czech Republic; Department of Sport Medicine, Third Faculty of Medicine, Charles University in Prague, CZ-100 00, Czech Republic. FAU - Mairal, Aline AU - Mairal A AD - Franco-Czech Laboratory for Clinical Research on Obesity, Third Faculty of Medicine, Prague, Czech Republic; Inserm, UMR1048, Obesity Research Laboratory, Institute of Metabolic and Cardiovascular Diseases, 31432 Toulouse, Cedex 4, France. FAU - Malisova, Lucia AU - Malisova L AD - Franco-Czech Laboratory for Clinical Research on Obesity, Third Faculty of Medicine, Prague, Czech Republic; Department of Sport Medicine, Third Faculty of Medicine, Charles University in Prague, CZ-100 00, Czech Republic. FAU - Stich, Vladimir AU - Stich V AD - Franco-Czech Laboratory for Clinical Research on Obesity, Third Faculty of Medicine, Prague, Czech Republic; Department of Sport Medicine, Third Faculty of Medicine, Charles University in Prague, CZ-100 00, Czech Republic. FAU - Langin, Dominique AU - Langin D AD - Franco-Czech Laboratory for Clinical Research on Obesity, Third 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. FAU - Rossmeislova, Lenka AU - Rossmeislova L AD - Franco-Czech Laboratory for Clinical Research on Obesity, Third Faculty of Medicine, Prague, Czech Republic; Department of Sport Medicine, Third Faculty of Medicine, Charles University in Prague, CZ-100 00, Czech Republic. Electronic address: Lenka.Rossmeislova@lf3.cuni.cz. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150324 PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (Endoplasmic Reticulum Chaperone BiP) RN - 0 (HSPA5 protein, human) RN - 0 (Lipids) RN - 11089-65-9 (Tunicamycin) RN - 67526-95-8 (Thapsigargin) SB - IM MH - Adipocytes/*cytology MH - *Cell Differentiation MH - Endoplasmic Reticulum/drug effects/*metabolism MH - Endoplasmic Reticulum Chaperone BiP MH - Humans MH - Lipids/*biosynthesis MH - Phosphorylation MH - *Stress, Physiological MH - Thapsigargin/pharmacology MH - Tunicamycin/pharmacology MH - Unfolded Protein Response OTO - NOTNLM OT - Adipocytes OT - Adipogenesis OT - Endoplasmic reticulum stress OT - Lipogenesis OT - Thapsigargin OT - Tunicamycin EDAT- 2015/03/31 06:00 MHDA- 2015/08/22 06:00 CRDT- 2015/03/28 06:00 PHST- 2015/03/04 00:00 [received] PHST- 2015/03/12 00:00 [accepted] PHST- 2015/03/28 06:00 [entrez] PHST- 2015/03/31 06:00 [pubmed] PHST- 2015/08/22 06:00 [medline] AID - S0006-291X(15)00546-X [pii] AID - 10.1016/j.bbrc.2015.03.090 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2015 May 8;460(3):684-90. doi: 10.1016/j.bbrc.2015.03.090. Epub 2015 Mar 24.