Proline oxidase-adipose triglyceride lipase pathway restrains adipose cell death and tissue inflammation

被引：61

作者：

Barbato, D. Lettieri ^{[1
]}

Aquilano, K. ^{[1
]}

Baldelli, S. ^{[2
]}

Cannata, S. M. ^{[1
]}

Bernardini, S. ^{[1
]}

Rotilio, G. ^{[2
]}

Ciriolo, M. R. ^{[1
,3
]}

机构：

[1] Univ Roma Tor Vergata, Dept Biol, I-00133 Rome, Italy

[2] Univ Telemat San Raffaele Roma, I-00166 Rome, Italy

[3] IRCCS San Raffaele, I-00166 Rome, Italy

来源：

CELL DEATH AND DIFFERENTIATION | 2014年 / 21卷 / 01期

关键词：

ageing; adipocytes; lipid signalling; mitochondrial metabolism; reactive oxygen species; starvation; FREE FATTY-ACIDS; EXTENDS LIFE-SPAN; PPAR-ALPHA; TRANSCRIPTION FACTOR; REGIONAL DIFFERENCES; INSULIN-RESISTANCE; 3T3-L1; ADIPOCYTES; OXIDATIVE STRESS; NUTRIENT STRESS; LIPOLYSIS;

D O I：

10.1038/cdd.2013.137

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The nutrient-sensing lipolytic enzyme adipose triglyceride lipase (ATGL) has a key role in adipose tissue function, and alterations in its activity have been implicated in many age-related metabolic disorders. In adipose tissue reduced blood vessel density is related to hypoxia state, cell death and inflammation. Here we demonstrate that adipocytes of poorly vascularized enlarged visceral adipose tissue (i.e. adipose tissue of old mice) suffer from limited nutrient delivery. In particular, nutrient starvation elicits increased activity of mitochondrial proline oxidase/dehydrogenase (POX/PRODH) that is causal in triggering a ROS-dependent induction of ATGL. We demonstrate that ATGL promotes the expression of genes related to mitochondrial oxidative metabolism (peroxisome proliferator-activated receptor-alpha, peroxisome proliferator-activated receptor-gamma coactivator-1 alpha), thus setting a metabolic switch towards fat utilization that supplies energy to starved adipocytes and prevents cell death, as well as adipose tissue inflammation. Taken together, these results identify ATGL as a stress resistance mediator in adipocytes, restraining visceral adipose tissue dysfunction typical of age-related metabolic disorders.

引用

页码：113 / 123

页数：11

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