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.
HighlightsTranslational landscape in DRG and spinal cord in SNI assay of neuropathic pain was established.ERK is a central hub of both transcriptionally and translationally controlled genes.Changes in translation efficiency and mRNA levels occur in the opposite direction for multiple mRNAs.
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