NT-PGC-1α activation attenuates high-fat diet-induced obesity by enhancing brown fat thermogenesis and adipose tissue oxidative metabolism.
NT-PGC-1α activation attenuates high-fat diet-induced obesity by enhancing brown fat thermogenesis and adipose tissue oxidative metabolism.
复制标题
作者：
Jun HJ;Joshi Y;Patil Y;Noland RC;Chang JS
转录辅激活因子过氧化物酶体增殖物激活受体γ辅激活因子（PGC）-1α及其剪接变体N末端（NT）-PGC-1α通过转录诱导产热基因和线粒体能量代谢相关基因来调节适应性产热。我们之前报道过，全长PGC-1α（FL-PGC-1α）在FL-PGC-1α−/−小鼠中对冷诱导的非颤抖性产热有抑制作用，因为一种稍短但功能等同的NT-PGC-1α（NT-PGC-1α254）完全补偿了棕色和白色脂肪组织中FL-PGC-1α的损失。在当前的研究中，我们用高脂饮食（HFD）挑战FL-PGC-1α-/-小鼠，以研究饮食诱导的产热对HFD诱导的肥胖的影响。尽管运动活动大幅减少，但FL-PGC-1α−/−小鼠表现出令人惊讶的减轻HFD诱导的肥胖的能力。FL-PGC-1α−/−小鼠的脂肪量减少与体温、能量消耗和全身脂肪酸氧化（FAO）的增加密切相关。从机制上讲，FL-PGC-1α−/−棕色脂肪组织氧化脂肪酸和以热量形式耗散能量的能力增加，与产热基因UCP 1和DIO 2的上调一致。此外，FL-PGC-1α-/-白色脂肪组织中FAO和脂解基因表达增强与脂肪组织中脂肪储存减少高度相关。总的来说，我们的数据强调了NT-PGC-1α通过增强饮食诱导的产热和FAO对饮食诱导的肥胖的保护作用。
The transcriptional coactivator peroxisome proliferator–activated receptor γ coactivator (PGC)-1α and its splice variant N terminal (NT)-PGC-1α regulate adaptive thermogenesis by transcriptional induction of thermogenic and mitochondrial genes involved in energy metabolism. We previously reported that full-length PGC-1α (FL-PGC-1α) is dispensable for cold-induced nonshivering thermogenesis in FL-PGC-1α−/− mice, since a slightly shorter but functionally equivalent form of NT-PGC-1α (NT-PGC-1α254) fully compensates for the loss of FL-PGC-1α in brown and white adipose tissue. In the current study, we challenged FL-PGC-1α−/− mice with a high-fat diet (HFD) to investigate the effects of diet-induced thermogenesis on HFD-induced obesity. Despite a large decrease in locomotor activity, FL-PGC-1α−/− mice exhibited the surprising ability to attenuate HFD-induced obesity. Reduced fat mass in FL-PGC-1α−/− mice was closely associated with an increase in body temperature, energy expenditure, and whole-body fatty acid oxidation (FAO). Mechanistically, FL-PGC-1α−/− brown adipose tissue had an increased capacity to oxidize fatty acids and dissipate energy as heat, in accordance with upregulation of thermogenic genes UCP1 and DIO2. Furthermore, augmented expression of FAO and lipolytic genes in FL-PGC-1α−/− white adipose tissue was highly correlated with decreased fat storage in adipose tissue. Collectively, our data highlight a protective effect of NT-PGC-1α on diet-induced obesity by enhancing diet-induced thermogenesis and FAO.
登录
查看更多内容
影响因子：
4.8
作者：
Golozoubova, V;Hohtola, E;Nedergaard, J
通讯作者：
Nedergaard, J
影响因子：
4.8
作者：
Hamann, A;Flier, JS;Lowell, BB
通讯作者：
Lowell, BB
影响因子：
64.5
作者：
Lin, JD;Wu, PH;Spiegelman, BM
通讯作者：
Spiegelman, BM
影响因子：
4.8
作者：
Martinez de Mena, Raquel;Scanlan, Thomas S.;Obregon, Maria-Jesus
通讯作者：
Obregon, Maria-Jesus
影响因子：
15.9
作者：
Kopecky, J;Clarke, G;Kozak, LP
通讯作者：
Kozak, LP