title: Emerging role of autophagy in mediating widespread actions of ADIPOQ/adiponectin.
abstract: 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.
authors.affiliation: a State Key Laboratory of Pharmaceutical Biotechnology; University of Hong Kong ; Hong Hong.
authors.forename: Aimin
authors.initials: A
authors.lastname: Xu
authors.forename: Gary
authors.initials: G
authors.lastname: Sweeney
mesh_terms: D052242:Adiponectin / Q000378:metabolism*; D000818:Animals; D001343:Autophagy / Q000502:physiology*; D000071187:Autophagy-Related Protein 5; D000071189:Autophagy-Related Protein-1 Homolog; D059305:Diet, High-Fat; D007333:Insulin Resistance / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D018485:Muscle Fibers, Skeletal / Q000378:metabolism*; D010766:Phosphorylation / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D052242:Adiponectin; C499919:Adipoq protein, mouse; C495773:Atg5 protein, mouse; D000071187:Autophagy-Related Protein 5; D008869:Microtubule-Associated Proteins; D000071189:Autophagy-Related Protein-1 Homolog; D017346:Protein Serine-Threonine Kinases; C112444:Ulk1 protein, mouse
keywords: adiponectin; autophagy; insulin sensitivity; metabolism