title: Adiponectin stimulates Rho-mediated actin cytoskeleton remodeling and glucose uptake via APPL1 in primary cardiomyocytes.
abstract: OBJECTIVE
  Adiponectin is known to confer its cardioprotective effects in obesity and type 2 diabetes, mainly by regulating glucose and fatty acid metabolism in cardiomyocytes. Dynamic actin cytoskeleton remodeling is involved in regulation of multiple biological functions, including glucose uptake. Here we investigated in neonatal cardiomyocytes whether adiponectin induced actin cytoskeleton remodeling and if this played a role in adiponectin-stimulated glucose uptake.
  
  
  METHODS
  Primary cardiomyocytes were treated with full-length and globular adiponectin (fAd and gAd, respectively).
  
  
  RESULTS
  Both fAd and gAd increased RhoA activity, phosphorylation of the Rho/ROCK signaling target cofilin and actin polymerization to form filamentous actin as determined by rhodamine-phallodin immunofluorescence and quantitative analysis of filamentous to globular actin ratio. Scanning electron microscopy also demonstrated structural remodeling. Adiponectin stimulated glucose uptake, was significantly abrogated in the presence of inhibitors of actin cytoskeleton remodeling (cytochalasin D) and Rho/ROCK signaling (C3 transferase, Y27632). We showed that adiponectin increased colocalization of actin and APPL1 and that actin remodeling, phosphorylation of AMPK, p38MAPK and cofilin, glucose uptake and oxidation were all attenuated after siRNA-mediated knockdown of APPL1.
  
  
  CONCLUSIONS
  We show that adiponectin mediates Rho/ROCK-dependent actin cytoskeleton remodeling to increase glucose uptake and metabolism via APPL1 signaling.
authors.affiliation: Department of Biology, York University, Toronto, Canada.
authors.forename: Rengasamy
authors.initials: R
authors.lastname: Palanivel
authors.affiliation: Department of Biology, York University, Toronto, Canada.
authors.forename: Riya
authors.initials: R
authors.lastname: Ganguly
authors.affiliation: Department of Biology, York University, Toronto, Canada.
authors.forename: Subat
authors.initials: S
authors.lastname: Turdi
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, and Department of Medicine, the University of Hong Kong.
authors.forename: Aimin
authors.initials: A
authors.lastname: Xu
authors.affiliation: Department of Biology, York University, Toronto, Canada. Electronic address: gsweeney@yorku.ca.
authors.forename: Gary
authors.initials: G
authors.lastname: Sweeney
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism* / Q000502:physiology; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D052242:Adiponectin / Q000378:metabolism*; D000818:Animals; D005947:Glucose / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010766:Phosphorylation / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology; D054460:rho-Associated Kinases / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D052242:Adiponectin; C515694:Appl1 protein, rat; D009419:Nerve Tissue Proteins; D054460:rho-Associated Kinases; D005947:Glucose
keywords: APPL1; Actin cytoskeleton; Adiponectin; Cardiomyocyte; Glucose uptake