体重是否是“稳态”调控的?——来自Rcan2的启示

Is body weight "homeostatically" regulated?——a clue from Rcan2

体重及脂肪组织被认为受到能量稳态机制的严格调控,即脂肪细胞分泌的、显示机体脂肪含量的信号分子——瘦素通过下丘脑的信号通路对体重进行双向调控.近几十年来肥胖在全球暴发,肥胖个体中过量的瘦素并未抑制体重的增长,该现象被归因于"瘦素抵抗".然而最近有证据显示,肥胖发生过程中瘦素功能没有改变,瘦素抵抗不存在.因此体重是否受稳态调控存有争议.而本研究组发现一种依赖R c a n 2基因且不受瘦素抑制的增加摄食及体重的机制,伴有高脂肪食物时可导致体重快速增加进而产生肥胖,该发现可为肥胖的流行提供新的解释.

Body weight and adipose mass are thought to be tightly regulated by homeostatic mechanisms,in which leptin,an adipocyte secreted hormone,circulates in concentrations proportional to body fat content and thereby regulates body weight through hypothalamic pathways in a bi-directional manner.However,obesity has become global epidemic over the past several decades,despite of high circulating leptin levels among the obese population.This phenomenon was considered as a result of ＂leptin resistance＂ in the central nervous system.Intriguingly,recent evidences show that leptin is still functional under the obese condition,therefore the development of obesity is not due to ＂leptin resistance＂.To date,whether body weight is homeostatically regulated is still controversial.Recently,we found that Rcan2 regulated food intake via a leptin-independent pathway,and could promote a rapid weight gain in mice when fed with a high-fat diet,which provides a novel insight into the mechanisms of obesity epidemic.