Xu Aimin, Sweeney Gary
a State Key Laboratory of Pharmaceutical Biotechnology; University of Hong Kong ; Hong Hong.
Autophagy. 2015 Apr 3;11(4):723-4. doi: 10.1080/15548627.2015.1034418.
Autophagy can dictate changes in cell metabolism via numerous mechanisms. ADIPOQ/adiponectin has been extensively characterized to have beneficial metabolic effects, both via INS/insulin-sensitizing and INS-independent actions. Our recent work examined the regulation of skeletal muscle autophagy by ADIPOQ and the functional significance. We showed that ADIPOQ directly stimulates autophagic flux in cultured skeletal muscle cells via an AMPK-dependent signaling pathway leading to phosphorylation of ULK1 (Ser555). Pharmacological inhibition of autophagy or overexpressing an inactive mutant of ATG5 to create an autophagy-deficient cell model reduces INS sensitivity. A high-fat diet (HFD) does not induce skeletal muscle autophagy in Adipoq knockout (Ad-KO) mice, whereas it does in wild-type (WT) mice, although ADIPOQ replenishment in Ad-KO mice stimulates autophagy. Changes in skeletal muscle autophagy correlate well with peripheral INS sensitivity and glucose metabolism. Thus, ADIPOQ stimulates autophagic flux in skeletal muscle, which likely represents one important mechanism mediating multiple favorable metabolic effects.
自噬可通过多种机制决定细胞代谢的变化。脂联素（ADIPOQ/adiponectin）已被广泛证实具有有益的代谢作用，这是通过胰岛素（INS/insulin）增敏作用和不依赖胰岛素的作用实现的。我们最近的研究探讨了脂联素对骨骼肌自噬的调节及其功能意义。我们发现，脂联素通过一条依赖于AMPK的信号通路直接刺激培养的骨骼肌细胞中的自噬流，该通路导致ULK1（Ser555）磷酸化。对自噬进行药理抑制或过表达ATG5的无活性突变体以创建自噬缺陷细胞模型会降低胰岛素敏感性。高脂饮食（HFD）不会在脂联素基因敲除（Ad-KO）小鼠中诱导骨骼肌自噬，而在野生型（WT）小鼠中则会诱导，不过在Ad-KO小鼠中补充脂联素会刺激自噬。骨骼肌自噬的变化与外周胰岛素敏感性和葡萄糖代谢密切相关。因此，脂联素刺激骨骼肌中的自噬流，这可能是介导多种有利代谢作用的一个重要机制。
