Department of Nutritional Science and Toxicology, University of California-Berkeley, CA 94720, USA.
Cell Metab. 2011 Jun 8;13(6):739-48. doi: 10.1016/j.cmet.2011.05.002.
While fatty acids (FAs) released by white adipose tissue (WAT) provide energy for other organs, lipolysis is also critical in brown adipose tissue (BAT), generating FAs for oxidation and UCP-1 activation for thermogenesis. Here we show that adipose-specific ablation of desnutrin/ATGL in mice converts BAT to a WAT-like tissue. These mice exhibit severely impaired thermogenesis with increased expression of WAT-enriched genes but decreased BAT genes, including UCP-1 with lower PPARα binding to its promoter, revealing the requirement of desnutrin-catalyzed lipolysis for maintaining a BAT phenotype. We also show that desnutrin is phosphorylated by AMPK at S406, increasing TAG hydrolase activity, and provide evidence for increased lipolysis by AMPK phosphorylation of desnutrin in adipocytes and in vivo. Despite adiposity and impaired BAT function, desnutrin-ASKO mice have improved hepatic insulin sensitivity with lower DAG levels. Overall, desnutrin is phosphorylated/activated by AMPK to increase lipolysis and brings FA oxidation and UCP-1 induction for thermogenesis.
虽然白色脂肪组织（WAT）释放的脂肪酸（FAs）为其他器官提供能量，但脂肪分解在棕色脂肪组织（BAT）中也至关重要，它产生 FAs 用于氧化和 UCP-1 激活以产热。在这里，我们表明，脂肪组织特异性敲除小鼠的去脂素/ATGL 将 BAT 转化为类似于 WAT 的组织。这些小鼠表现出严重的产热受损，WAT 丰富基因的表达增加，但 BAT 基因减少，包括 UCP-1 的 PPARα 与其启动子结合减少，这表明去脂素催化的脂肪分解对于维持 BAT 表型是必需的。我们还表明，AMPK 在 S406 处使去脂素磷酸化，增加 TAG 水解酶活性，并提供证据表明 AMPK 磷酸化去脂素可增加脂肪细胞和体内的脂肪分解。尽管肥胖和 BAT 功能受损，去脂素-ASKO 小鼠的肝脏胰岛素敏感性提高，DAG 水平降低。总的来说，AMPK 使去脂素磷酸化/激活以增加脂肪分解，并带来 FA 氧化和 UCP-1 诱导以产热。
