Perilipin 5 links mitochondrial uncoupled respiration in brown fat to healthy white fat remodeling and systemic glucose tolerance.
Perilipin 5 links mitochondrial uncoupled respiration in brown fat to healthy white fat remodeling and systemic glucose tolerance.
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DOI：
10.1038/s41467-021-23601-2
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发表时间：
2021-06-03
影响因子：
16.6
通讯作者：
Bickel PE
中科院分区：
文献类型：
--
作者：
Gallardo-Montejano VI;Yang C;Hahner L;McAfee JL;Johnson JA;Holland WL;Fernandez-Valdivia R;Bickel PE
小鼠或人类暴露于寒冷环境会促进棕色脂肪组织（BAT）在组织学、脂质含量、基因表达以及线粒体质量和功能方面发生显着变化。在此，我们报告，在小鼠暴露于寒冷时，BAT 中的脂滴外壳蛋白 Perilipin 5 (PLIN5) 显着增加。为了了解冷诱导 PLIN5 的功能意义，我们创建并表征了功能获得和丧失功能的小鼠模型。在小鼠 BAT 中强制表达 PLIN5 可以模拟寒冷对线粒体嵴堆积和解偶联底物驱动呼吸的影响。 PLIN5 对于冷应激期间维持线粒体嵴结构和呼吸功能是必需的。我们进一步表明，促进 BAT 中的 PLIN5 功能与皮下白色脂肪组织的健康重塑以及全身葡萄糖耐量和饮食诱导的肝脂肪变性的改善有关。这些观察结果将为未来寻求利用产热脂肪组织作为 2 型糖尿病、肥胖症和非酒精性脂肪肝的治疗靶点的策略提供信息。 Perilipin 5 是一种脂滴蛋白，与细胞核中的 PGC1α 相互作用来调节线粒体代谢。在这里，作者使用基因工程小鼠模型来确定 Perilipin 5 的生理作用，并表明它调节线粒体对寒冷的适应以及全身能量代谢。
Exposure of mice or humans to cold promotes significant changes in brown adipose tissue (BAT) with respect to histology, lipid content, gene expression, and mitochondrial mass and function. Herein we report that the lipid droplet coat protein Perilipin 5 (PLIN5) increases markedly in BAT during exposure of mice to cold. To understand the functional significance of cold-induced PLIN5, we created and characterized gain- and loss-of-function mouse models. Enforcing PLIN5 expression in mouse BAT mimics the effects of cold with respect to mitochondrial cristae packing and uncoupled substrate-driven respiration. PLIN5 is necessary for the maintenance of mitochondrial cristae structure and respiratory function during cold stress. We further show that promoting PLIN5 function in BAT is associated with healthy remodeling of subcutaneous white adipose tissue and improvements in systemic glucose tolerance and diet-induced hepatic steatosis. These observations will inform future strategies that seek to exploit thermogenic adipose tissue as a therapeutic target for type 2 diabetes, obesity, and nonalcoholic fatty liver disease. Perilipin 5 is a lipid droplet protein that interacts with PGC1α in the nucleus to regulate mitochondrial metabolism. Here the authors use genetically engineered mouse models to determine the physiologic role of Perilipin 5, and show that it regulates mitochondrial adaptations to cold, as well as systemic energy metabolism.
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影响因子：
29
作者：
Kajimura S;Spiegelman BM;Seale P
通讯作者：
Seale P
DOI：
10.1126/science.1190816
发表时间：
2010-05-28
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Ishibashi J;Seale P
通讯作者：
Seale P
影响因子：
16.6
作者：
Gallardo-Montejano VI;Saxena G;Kusminski CM;Yang C;McAfee JL;Hahner L;Hoch K;Dubinsky W;Narkar VA;Bickel PE
通讯作者：
Bickel PE
影响因子：
64.8
作者：
Enerback, S;Jacobsson, A;Kozak, LP
通讯作者：
Kozak, LP
影响因子：
82.9
作者：
Czech MP
通讯作者：
Czech MP