title: Autophagy: roles in obesity-induced ER stress and adiponectin downregulation in adipocytes.
abstract: Accumulating evidence strongly suggests that autophagy, which is induced by endoplasmic reticulum (ER) stress in adipocytes, may play an important role in obesity-induced insulin resistance and type 2 diabetes. Obesity induces ER stress in mouse adipose tissue, which correlates with reduced adiponectin levels. In 3T3-L1 adipocytes, induction of ER stress is sufficient to promote autophagy-dependent adiponectin degradation. In contrast, suppressing ER stress increases adiponectin levels in 3T3-L1 adipocytes and alleviates high fat diet-induced adiponectin downregulation in mice. The ER stress-induced adiponectin downregulation can also be suppressed by overexpression of DsbA-L, a newly identified protein involved in promoting adiponectin multimerization and stability. Taken together, our results show that ER stress-induced autophagy provides an important mechanism underlying obesity-induced adiponectin downregulation in adipocytes. In addition, increasing the expression levels of DsbA-L could be an effective approach to improve adiponectin biosynthesis and stability, thus improving insulin sensitivity: in cells and in vivo.
authors.affiliation: Department of Pharmacology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
authors.forename: Lijun
authors.initials: L
authors.lastname: Zhou
authors.forename: Feng
authors.initials: F
authors.lastname: Liu
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000378:metabolism*; D052242:Adiponectin / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001343:Autophagy; D002470:Cell Survival; D015536:Down-Regulation / Q000235:genetics*; D004721:Endoplasmic Reticulum / Q000378:metabolism / Q000473:pathology*; D004734:Energy Metabolism; D006801:Humans; D051379:Mice; D008954:Models, Biological; D009765:Obesity / Q000235:genetics* / Q000473:pathology*; D013312:Stress, Physiological
chemical_list: D052242:Adiponectin