产热
过氧化物酶体增殖物激活受体γ
脂肪生成
生物
褐色脂肪组织
自噬
产热素
内分泌学
PRDM16
内科学
细胞生物学
脂肪组织
过氧化物酶体
受体
生物化学
医学
细胞凋亡
作者
Alba Sabaté-Pérez,Montserrat Romero,Paula Sànchez‐Fernàndez‐de‐Landa,Stefania Carobbio,Michail Mouratidis,David Sala,Pablo Engel,Josep A. Villena,Sam Virtue,Antonio Vidal–Puig,Manuel Palacı́n,Xavier Testar,António Zorzano
出处
期刊:Autophagy
[Informa]
日期:2022-08-25
卷期号:19 (3): 904-925
被引量:4
标识
DOI:10.1080/15548627.2022.2111081
摘要
Brown adipose tissue (BAT) thermogenesis affects energy balance, and thereby it has the potential to induce weight loss and to prevent obesity. Here, we document a macroautophagic/autophagic-dependent mechanism of peroxisome proliferator-activated receptor gamma (PPARG) activity regulation that induces brown adipose differentiation and thermogenesis and that is mediated by TP53INP2. Disruption of TP53INP2-dependent autophagy reduced brown adipogenesis in cultured cells. In vivo specific-tp53inp2 ablation in brown precursor cells or in adult mice decreased the expression of thermogenic and mature adipocyte genes in BAT. As a result, TP53INP2-deficient mice had reduced UCP1 content in BAT and impaired maximal thermogenic capacity, leading to lipid accumulation and to positive energy balance. Mechanistically, TP53INP2 stimulates PPARG activity and adipogenesis in brown adipose cells by promoting the autophagic degradation of NCOR1, a PPARG co-repressor. Moreover, the modulation of TP53INP2 expression in BAT and in human brown adipocytes suggests that this protein increases PPARG activity during metabolic activation of brown fat. In all, we have identified a novel molecular explanation for the contribution of autophagy to BAT energy metabolism that could facilitate the design of therapeutic strategies against obesity and its metabolic complications.
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