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 journalArticlepeer-review

21 Scopus citations

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 - 2015

Keywords

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

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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