Deletion of the gene encoding G0/G1 switch protein 2 (G0s2) alleviates high-fat-diet-induced weight gain and insulin resistance, and promotes browning of white adipose tissue in mice

Wissal El-Assaad, Karim El-Kouhen, Amro H. Mohammad, Jieyi Yang, Masahiro Morita, Isabelle Gamache, Orval Mamer, Daina Avizonis, Nicole Hermance, Sander Kersten, Michel L. Tremblay, Michelle A. Kelliher, Jose G. Teodoro

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Conclusions/interpretation: Our data show that G0s2 is a physiological regulator of adiposity and energy metabolism and is a potential target in the treatment of obesity and insulin resistance.

Results: We report that G0s2 inhibits ATGL and regulates lipolysis and energy metabolism in vivo. G0s2−/− mice are lean, resistant to weight gain induced by a high-fat diet and are glucose tolerant and insulin sensitive. The white adipose tissue of G0s2−/− mice has enhanced lipase activity and adipocytes showed enhanced stimulated lipolysis. Energy metabolism in the G0s2−/− mice is shifted towards enhanced lipid metabolism and increased thermogenesis. G0s2−/− mice showed enhanced cold tolerance and increased expression of thermoregulatory and oxidation genes within white adipose tissue, suggesting enhanced ‘browning’ of the white adipose tissue.

Aims/hypothesis: Obesity is a global epidemic resulting from increased energy intake, which alters energy homeostasis and results in an imbalance in fat storage and breakdown. G0/G1 switch gene 2 (G0s2) has been recently characterised in vitro as an inhibitor of adipose triglyceride lipase (ATGL), the rate-limiting step in fat catabolism. In the current study we aim to functionally characterise G0s2 within the physiological context of a mouse model.

Methods: We generated a mouse model in which G0s2 was deleted. The homozygous G0s2 knockout (G0s2−/−) mice were studied over a period of 22 weeks. Metabolic variables were measured including body weight and body composition, food intake, glucose and insulin tolerance tests, energy metabolism and thermogenesis.

Original languageEnglish (US)
Pages (from-to)149-157
Number of pages9
JournalDiabetologia
Volume58
Issue number1
DOIs
StatePublished - Jan 1 2015
Externally publishedYes

Fingerprint

White Adipose Tissue
Gene Deletion
High Fat Diet
Weight Gain
Insulin Resistance
Energy Metabolism
Lipase
Proteins
Thermogenesis
Lipolysis
Obesity
Fats
Switch Genes
Insulin
Adiposity
Glucose Tolerance Test
Body Composition
Energy Intake
Lipid Metabolism
Adipocytes

Keywords

  • Adipose tissue browning
  • ATGL
  • Energy expenditure
  • G0s2
  • High-fat diet
  • Insulin resistance
  • Lipolysis
  • Obesity
  • Thermogenesis

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Deletion of the gene encoding G0/G1 switch protein 2 (G0s2) alleviates high-fat-diet-induced weight gain and insulin resistance, and promotes browning of white adipose tissue in mice. / El-Assaad, Wissal; El-Kouhen, Karim; Mohammad, Amro H.; Yang, Jieyi; Morita, Masahiro; Gamache, Isabelle; Mamer, Orval; Avizonis, Daina; Hermance, Nicole; Kersten, Sander; Tremblay, Michel L.; Kelliher, Michelle A.; Teodoro, Jose G.

In: Diabetologia, Vol. 58, No. 1, 01.01.2015, p. 149-157.

Research output: Contribution to journalArticle

El-Assaad, W, El-Kouhen, K, Mohammad, AH, Yang, J, Morita, M, Gamache, I, Mamer, O, Avizonis, D, Hermance, N, Kersten, S, Tremblay, ML, Kelliher, MA & Teodoro, JG 2015, 'Deletion of the gene encoding G0/G1 switch protein 2 (G0s2) alleviates high-fat-diet-induced weight gain and insulin resistance, and promotes browning of white adipose tissue in mice', Diabetologia, vol. 58, no. 1, pp. 149-157. https://doi.org/10.1007/s00125-014-3429-z
El-Assaad, Wissal ; El-Kouhen, Karim ; Mohammad, Amro H. ; Yang, Jieyi ; Morita, Masahiro ; Gamache, Isabelle ; Mamer, Orval ; Avizonis, Daina ; Hermance, Nicole ; Kersten, Sander ; Tremblay, Michel L. ; Kelliher, Michelle A. ; Teodoro, Jose G. / Deletion of the gene encoding G0/G1 switch protein 2 (G0s2) alleviates high-fat-diet-induced weight gain and insulin resistance, and promotes browning of white adipose tissue in mice. In: Diabetologia. 2015 ; Vol. 58, No. 1. pp. 149-157.
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AU - El-Kouhen, Karim

AU - Mohammad, Amro H.

AU - Yang, Jieyi

AU - Morita, Masahiro

AU - Gamache, Isabelle

AU - Mamer, Orval

AU - Avizonis, Daina

AU - Hermance, Nicole

AU - Kersten, Sander

AU - Tremblay, Michel L.

AU - Kelliher, Michelle A.

AU - Teodoro, Jose G.

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KW - Thermogenesis

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