载脂蛋白 CETP 的新作用：通过增强脂肪分解和棕色脂肪组织活性来减轻肥胖。

Novel role of cholesteryl ester transfer protein (CETP): attenuation of adiposity by enhancing lipolysis and brown adipose tissue activity.

机构信息

Department of Structural and Functional Biology, Institute of Biology, State University of Campinas, Campinas, SP, Brazil; Obesity and Comorbidities Research Center, Institute of Biology, State University of Campinas, Campinas, SP, Brazil.

Department of Structural and Functional Biology, Institute of Biology, State University of Campinas, Campinas, SP, Brazil.

出版信息

Metabolism. 2021 Jan;114:154429. doi: 10.1016/j.metabol.2020.154429. Epub 2020 Nov 6.

DOI:10.1016/j.metabol.2020.154429

PMID:33166579

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.

摘要

目的

CETP 的全身功能已得到充分表征。CETP 血浆活性降低了 HDL 胆固醇，从而增加了动脉粥样硬化的风险。在这里，我们研究了 CETP 表达是否调节肥胖。

方法

比较了 CETP 转基因和非转基因小鼠以及用 CETP 中和抗体处理的仓鼠的体脂和能量代谢相关测定和基因/蛋白表达。

结果

我们发现表达人 CETP 的转基因小鼠的白色脂肪组织质量和瘦素血症低于非转基因（NTg）同窝仔。在体力活动、食物摄入、脂肪粪便排泄、脂肪生成或脂肪组织中外源脂质积累方面没有差异。然而，CETP 小鼠的脂肪分解率和全身能量消耗增加。相应地，内脏和棕色脂肪组织（BAT）中的脂肪分解相关基因表达和蛋白含量增加。此外，我们还验证了 BAT 温度和耗氧量的增加。这些结果在另外两种动物模型中得到了证实：1）用 CETP 中和抗体处理的仓鼠，2）表达食蟹猴 CETP 的另一个独立转基因小鼠系。