title: Stress of endoplasmic reticulum modulates differentiation and lipogenesis of human adipocytes.
abstract: 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.
authors: 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.
authors: Michal
authors: M
authors: Koc
authors: 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.
authors: Veronika
authors: V
authors: Mayerová
authors: 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.
authors: Jana
authors: J
authors: Kračmerová
authors: 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.
authors: Aline
authors: A
authors: Mairal
authors: 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.
authors: Lucia
authors: L
authors: Mališová
authors: 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.
authors: Vladimír
authors: V
authors: Štich
authors: 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.
authors: Dominique
authors: D
authors: Langin
authors: 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.
authors: Lenka
authors: L
authors: Rossmeislová
mesh_terms: D017667:Adipocytes / Q000166:cytology*; D002454:Cell Differentiation; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism*; D000091342:Endoplasmic Reticulum Chaperone BiP; D006801:Humans; D008055:Lipids / Q000096:biosynthesis*; D010766:Phosphorylation; D013312:Stress, Physiological; D019284:Thapsigargin / Q000494:pharmacology; D014415:Tunicamycin / Q000494:pharmacology; D056811:Unfolded Protein Response
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D008055:Lipids; D014415:Tunicamycin; D019284:Thapsigargin
keywords: Adipocytes; Adipogenesis; Endoplasmic reticulum stress; Lipogenesis; Thapsigargin; Tunicamycin