Mechanisms
A novel anti-adipogenic role for CETP: it boosts brown fat activity and lipolysis to reduce body fat, across three animal models (Metabolism 2021)
Original title: Novel role of cholesteryl ester transfer protein (CETP): attenuation of adiposity by enhancing lipolysis and brown adipose tissue activity
The systemic effect of CETP on lowering HDL cholesterol is well established, but this study asked whether CETP also affects body adiposity directly. Human CETP-expressing transgenic mice had less white adipose tissue mass and lower plasma leptin than non-transgenic littermates, with no differences in physical activity, food intake, faecal fat excretion, lipogenesis or exogenous lipid accumulation in fat depots. Instead, adipose lipolysis and whole-body energy expenditure were elevated, accompanied by increased lipolysis-related gene and protein expression in visceral and brown adipose tissue, and higher brown adipose tissue temperature and oxygen consumption. The findings were confirmed in hamsters treated with a CETP-neutralising antibody and in an independent line of mice expressing simian CETP. The authors conclude CETP has a previously unrecognised anti-adipogenic role, working through enhanced lipolysis and brown fat activation rather than through its established lipid-transfer function.
Original abstract
Objective: The systemic function of CETP has been well characterized. CETP plasma activity reduces HDL cholesterol and thus increases the risk of atherosclerosis. Here, we investigated whether CETP expression modulate adiposity.
Methods: Body adiposity and energy metabolism related assays and gene/protein expression were compared in CETP transgenic and non-transgenic mice and in hamsters treated with CETP neutralizing antibody.
Results: We found that transgenic mice expressing human CETP present less white adipose tissue mass and lower leptinemia than nontransgenic (NTg) littermates. No differences were found in physical activity, food intake, fat fecal excretion, lipogenesis or exogenous lipid accumulation in adipose depots. Nonetheless, adipose lipolysis rates and whole-body energy expenditure were elevated in CETP mice. In accordance, lipolysis-related gene expression and protein content were increased in visceral and brown adipose tissue (BAT). In addition, we verified increased BAT temperature and oxygen consumption. These results were confirmed in two other animal models: 1) hamsters treated with CETP neutralizing antibody and 2) an independent line of transgenic mice expressing simian CETP.
Conclusions: These findings reveal a novel anti-adipogenic role for CETP.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.