skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

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 dosemore » 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. - Highlights: • High intensity ERS inhibits lipogenic capacity of adipocytes. • ERS impairs adipogenesis when present in early stages of adipogenesis. • Lipogenesis in mature adipocytes is not influenced by chronic low intensity ERS.« less

Authors:
; ;  [1];  [2];  [1];  [3]; ;  [1];  [2];  [1];  [3];  [3];  [3];  [1];  [2]
  1. Franco-Czech Laboratory for Clinical Research on Obesity, Third Faculty of Medicine, Prague (Czech Republic)
  2. (Czech Republic)
  3. (France)
Publication Date:
OSTI Identifier:
22462038
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 460; Journal Issue: 3; Other Information: Copyright (c) 2015 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ACETIC ACID; ADIPOSE TISSUE; CHRONIC EXPOSURE; ENDOPLASMIC RETICULUM; ERBIUM SULFIDES; GENES; GLUCOSE; HUMAN POPULATIONS; IN VITRO; LIPIDS; LIVER; MESSENGER-RNA; METABOLIC DISEASES; PHOSPHORYLATION; PROTEINS; SENSORS; STORAGE; STRESSES

Citation Formats

Koc, Michal, Mayerová, Veronika, Kračmerová, Jana, Department of Sport Medicine, Third Faculty of Medicine, Charles University in Prague, CZ-100 00, Mairal, Aline, Inserm, UMR1048, Obesity Research Laboratory, Institute of Metabolic and Cardiovascular Diseases, 31432 Toulouse, Cedex 4, Mališová, Lucia, Štich, Vladimír, Department of Sport Medicine, Third Faculty of Medicine, Charles University in Prague, CZ-100 00, Langin, Dominique, Inserm, UMR1048, Obesity Research Laboratory, Institute of Metabolic and Cardiovascular Diseases, 31432 Toulouse, Cedex 4, University of Toulouse, UMR1048, Paul Sabatier University, 31432 Toulouse, Cedex 4, Toulouse University Hospitals, Department of Clinical Biochemistry, 31059 Toulouse, Cedex 9, Rossmeislová, Lenka, E-mail: Lenka.Rossmeislova@lf3.cuni.cz, and Department of Sport Medicine, Third Faculty of Medicine, Charles University in Prague, CZ-100 00. Stress of endoplasmic reticulum modulates differentiation and lipogenesis of human adipocytes. United States: N. p., 2015. Web. doi:10.1016/J.BBRC.2015.03.090.
Koc, Michal, Mayerová, Veronika, Kračmerová, Jana, Department of Sport Medicine, Third Faculty of Medicine, Charles University in Prague, CZ-100 00, Mairal, Aline, Inserm, UMR1048, Obesity Research Laboratory, Institute of Metabolic and Cardiovascular Diseases, 31432 Toulouse, Cedex 4, Mališová, Lucia, Štich, Vladimír, Department of Sport Medicine, Third Faculty of Medicine, Charles University in Prague, CZ-100 00, Langin, Dominique, Inserm, UMR1048, Obesity Research Laboratory, Institute of Metabolic and Cardiovascular Diseases, 31432 Toulouse, Cedex 4, University of Toulouse, UMR1048, Paul Sabatier University, 31432 Toulouse, Cedex 4, Toulouse University Hospitals, Department of Clinical Biochemistry, 31059 Toulouse, Cedex 9, Rossmeislová, Lenka, E-mail: Lenka.Rossmeislova@lf3.cuni.cz, & Department of Sport Medicine, Third Faculty of Medicine, Charles University in Prague, CZ-100 00. Stress of endoplasmic reticulum modulates differentiation and lipogenesis of human adipocytes. United States. doi:10.1016/J.BBRC.2015.03.090.
Koc, Michal, Mayerová, Veronika, Kračmerová, Jana, Department of Sport Medicine, Third Faculty of Medicine, Charles University in Prague, CZ-100 00, Mairal, Aline, Inserm, UMR1048, Obesity Research Laboratory, Institute of Metabolic and Cardiovascular Diseases, 31432 Toulouse, Cedex 4, Mališová, Lucia, Štich, Vladimír, Department of Sport Medicine, Third Faculty of Medicine, Charles University in Prague, CZ-100 00, Langin, Dominique, Inserm, UMR1048, Obesity Research Laboratory, Institute of Metabolic and Cardiovascular Diseases, 31432 Toulouse, Cedex 4, University of Toulouse, UMR1048, Paul Sabatier University, 31432 Toulouse, Cedex 4, Toulouse University Hospitals, Department of Clinical Biochemistry, 31059 Toulouse, Cedex 9, Rossmeislová, Lenka, E-mail: Lenka.Rossmeislova@lf3.cuni.cz, and Department of Sport Medicine, Third Faculty of Medicine, Charles University in Prague, CZ-100 00. Fri . "Stress of endoplasmic reticulum modulates differentiation and lipogenesis of human adipocytes". United States. doi:10.1016/J.BBRC.2015.03.090.
@article{osti_22462038,
title = {Stress of endoplasmic reticulum modulates differentiation and lipogenesis of human adipocytes},
author = {Koc, Michal and Mayerová, Veronika and Kračmerová, Jana and Department of Sport Medicine, Third Faculty of Medicine, Charles University in Prague, CZ-100 00 and Mairal, Aline and Inserm, UMR1048, Obesity Research Laboratory, Institute of Metabolic and Cardiovascular Diseases, 31432 Toulouse, Cedex 4 and Mališová, Lucia and Štich, Vladimír and Department of Sport Medicine, Third Faculty of Medicine, Charles University in Prague, CZ-100 00 and Langin, Dominique and Inserm, UMR1048, Obesity Research Laboratory, Institute of Metabolic and Cardiovascular Diseases, 31432 Toulouse, Cedex 4 and University of Toulouse, UMR1048, Paul Sabatier University, 31432 Toulouse, Cedex 4 and Toulouse University Hospitals, Department of Clinical Biochemistry, 31059 Toulouse, Cedex 9 and Rossmeislová, Lenka, E-mail: Lenka.Rossmeislova@lf3.cuni.cz and Department of Sport Medicine, Third Faculty of Medicine, Charles University in Prague, CZ-100 00},
abstractNote = {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. - Highlights: • High intensity ERS inhibits lipogenic capacity of adipocytes. • ERS impairs adipogenesis when present in early stages of adipogenesis. • Lipogenesis in mature adipocytes is not influenced by chronic low intensity ERS.},
doi = {10.1016/J.BBRC.2015.03.090},
journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 3,
volume = 460,
place = {United States},
year = {2015},
month = {5}
}