Department of Biology, University of Rome Tor Vergata, via della Ricerca Scientifica, 00133 Rome, Italy.
Cell Death Differ. 2014 Jan;21(1):113-23. doi: 10.1038/cdd.2013.137. Epub 2013 Oct 4.
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-α, peroxisome proliferator-activated receptor-γ coactivator-1α), 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.
营养感应脂肪酶脂肪甘油三酯脂肪酶（ATGL）在脂肪组织功能中具有关键作用，其活性的改变与许多与年龄相关的代谢紊乱有关。在脂肪组织中，血管密度的降低与缺氧状态、细胞死亡和炎症有关。在这里，我们证明了血管化不良的增大内脏脂肪组织（即老年小鼠的脂肪组织）中的脂肪细胞受到有限的营养供应。特别是，营养饥饿会引起线粒体脯氨酸氧化酶/脱氢酶（POX/PRODH）活性的增加，这是触发活性氧依赖的 ATGL 诱导的原因。我们证明 ATGL 促进与线粒体氧化代谢相关的基因的表达（过氧化物酶体增殖物激活受体-α、过氧化物酶体增殖物激活受体-γ 共激活剂-1α），从而使代谢向脂肪利用转变，为饥饿的脂肪细胞提供能量，并防止细胞死亡和脂肪组织炎症。总之，这些结果表明 ATGL 是脂肪细胞中的应激抵抗介质，限制了与年龄相关的代谢紊乱相关的内脏脂肪组织功能障碍。
