Mice lacking G0S2 are lean and cold-tolerant

Ma, Tian; Lopez‐Aguiar, Alexandra G.; Li, Aihua; Lu, Yun; Sekula, David; Nattie, Eugene E.; Freemantle, Sarah J.; Dmitrovsky, Ethan

doi:10.4161/cbt.28251

Cited by 34 publications

(30 citation statements)

References 31 publications

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“…In this model, overexpression of G0S2 in adipocytes rendered the mice unable to maintain their body temperature at 4°C, probably due to the increased fat deposition in these mice. A new report also showed G0S2 regulation of thermogenesis and showed an increase in brown-like and oxidation genes in brown adipose tissue in G0S2 −/− mice [44]. …”

Section: Discussionmentioning

confidence: 99%

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

et al. 2014

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Aims/hypothesis Obesity is a global epidemic resulting from increased energy intake, leading to increased circulating free fatty acids, altering energy homeostasis and resulting in an imbalance in fat storage and breakdown. G0/G1 switch gene 2 (G0S2) has been recently characterized 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 characterize G0S2 within the physiological context of a mouse model. Methods We generated a mouse model in which G0S2 was deleted. G0S2 knockout mice were studied over a period of 22 weeks. Metabolic parameters were measured including body weight and body composition, food intake, glucose and insulin tolerance tests, energy metabolism and thermogenesis. Results We report that G0S2 inhibits ATGL and regulates lipolysis and energy metabolism in vivo. G0S2-knockout mice are lean, resistant to weight gain induced by high fat diet feeding and are glucose tolerant and insulin sensitive. White adipose tissues of G0S2-knockout mice have enhanced lipase activity and adipocytes showed enhanced stimulated lipolysis. Energy metabolism in the knockout mice is shifted toward enhanced lipid metabolism and increased thermogenesis. G0S2 knockout mice showed enhanced cold tolerance and increased expression of thermoregulatory and oxidation genes within white adipose tissue suggesting enhanced “browning” of the knockout-white adipose tissues. 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.

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Section: Discussionmentioning

confidence: 99%

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

et al. 2014

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“…During fasting, G0S2 is upregulated in the liver, where it acts critically to coordinate hepatic substrate utilization by decreasing the amount of available FAs and increasing the rates of glycogen breakdown (17)(18)(19). Specifically, global KO of G0S2 in mice leads to an impaired hepatic fasting response in terms of TG accumulation and glycogen depletion, along with enhanced adipose lipolysis (20)(21)(22). Mice with liver-specific G0S2 ablation exhibit increased hepatic ATGL-mediated TG hydrolysis and FA oxidation, along with decreased TG storage upon fasting (20).…”

Section: Introductionmentioning

confidence: 99%

Liver X receptor α mediates hepatic triglyceride accumulation through upregulation of G0/G1 Switch Gene 2 expression

Heckmann¹,

Zhang²,

Saarinen³

et al. 2017

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“…This was explained by increased β-oxidation and mitochondrial uncoupling, leading to increased energy expenditure and thermogenesis. The work of El-Assaad et al confirms and adds to previous studies showing that mice lacking G0S2 are lean, cold-tolerant and protected against HFD-induced insulin resistance [9,10]. Hence, G0S2 can be considered as key regulator of energy homeostasis, controlling both fatty acid availability and fatty acid oxidation.…”

mentioning

confidence: 58%