title: Roles and tissue source of adiponectin involved in lifestyle modifications.
abstract: BACKGROUND
  Calorie restriction and endurance exercise are known robust lifestyle modifications that delay the onset of type 2 diabetes and metabolic syndrome, however, its protective mechanism needs to be elucidated.
  
  
  METHODS
  To investigate the role of adiponectin in lifestyle modifications, male Sprague-Dawley rats were divided into groups of caloric restriction, exercise, and control for a 6-month intervention. Tissue and serum adiponectin levels, tissue expression of SIRT1, AMP-activated protein kinase (AMPK)α phosphorylation and AdipoR1, and insulin sensitivity were determined. All effects of adiponectin found in vivo were confirmed by L6 myoblast cells cultured with serum from a rat that received an intervention or by L6 cells with an AdipoR1 knockdown.
  
  
  RESULTS
  Circulating adiponectin levels increased twofold to threefold in those rats in the caloric restriction and aerobic exercise groups, and adiponectin expression increased significantly not only in adipose tissue but also in skeletal muscle. The enhancement of SIRT1, AdipoR1 expression, and AMPKα phosphorylation in the skeletal muscle of the rats that underwent an intervention was simulated in the L6 myoblast cells cultured with serum from the intervention rats. The transferable effects of adiponectin in the serum were confirmed by blunting these effects in L6 myoblast cells upon knockdown of AdipoR1 or neutralizing the serum with an anti-adiponectin antibody. Adiponectin also exhibited a dose-dependent induction of its own receptor. The induction of AdipoR1 and SIRT1 expression and AMPKα phosphorylation by adiponectin was blunted when AMPKα, SIRT1, or AdipoR1, respectively, were knocked down.
  
  
  CONCLUSIONS
  An elevated muscle-derived adiponectin can be attributed to lifestyle modifications. Adiponectin, which triggers the adiponectin receptor1 (AdipoR1) and its downstream targets AMPKα and SIRT1, was involved in the lifestyle modifications and control of type 2 diabetes.
authors.affiliation: Graduate School of Peking Union Medical College and Chinese Academy of Medical Science, Beijing, China
authors.forename: Yang
authors.initials: Y
authors.lastname: Dai
authors.forename: Jing
authors.initials: J
authors.lastname: Pang
authors.forename: Huan
authors.initials: H
authors.lastname: Gong
authors.forename: Wei
authors.initials: W
authors.lastname: Fan
authors.forename: Tie-Mei
authors.initials: TM
authors.lastname: Zhang
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D052242:Adiponectin / Q000097:blood / Q000378:metabolism*; D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D031204:Caloric Restriction; D002460:Cell Line; D003924:Diabetes Mellitus, Type 2 / Q000517:prevention & control; D055785:Gene Knockdown Techniques; D007333:Insulin Resistance; D008019:Life Style; D008055:Lipids / Q000097:blood; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism; D032446:Myoblasts / Q000378:metabolism; D005082:Physical Exertion; D051381:Rats; D017207:Rats, Sprague-Dawley; D054419:Receptors, Adiponectin / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D056564:Sirtuin 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D052242:Adiponectin; C499920:Adipoq protein, rat; D008055:Lipids; D054419:Receptors, Adiponectin; C504339:adiponectin receptor 1, rat; D055372:AMP-Activated Protein Kinases; C488368:Sirt1 protein, rat; D056564:Sirtuin 1