title: Muscle-specific overexpression of AdipoR1 or AdipoR2 gives rise to common and discrete local effects whilst AdipoR2 promotes additional systemic effects.
abstract: Hypoadiponectinemia and adiponectin resistance are implicated in the aetiology of obesity-related cardiometabolic disorders, hence represent a potential therapeutic axis. Here we characterised the effects of in vivo electrotransfer-mediated overexpression of the adiponectin receptors, AdipoR1 or AdipoR2, into tibialis anterior muscle (TAM) of lean or obese mice. In lean mice, TAM-specific overexpression of AdipoR1 (TAMR1) or AdipoR2 (TAMR2) increased phosphorylation of AMPK, AKT and ERK and expression of the insulin responsive glucose transporter glut4. In contrast, onlyTAMR2 increased pparα and a target gene acox1. These effects were decreased in obese mice despite no reduction in circulating adiponectin levels.TAMR2 also increased expression of adipoQ in TAM of lean and obese mice. Furthermore, in obese miceTAMR2 promoted systemic effects including; decreased weight gain; reduced epididymal fat mass and inflammation; increased epididymal adipoQ expression; increased circulating adiponectin. Collectively, these results demonstrate that AdipoR1 and AdipoR2 exhibit overlapping and distinct effects in skeletal muscle consistent with enhanced adiponectin sensitivity but these appear insufficient to ameliorate established obesity-induced adiponectin resistance. We also identify systemic effects uponTAMR2 in obese mice and postulate these are mediated by altered myokine production. Further studies are warranted to investigate this possibility which may reveal novel therapeutic approaches.
authors.affiliation: University of Queensland, Mater Research Institute-UQ, Brisbane, QLD 4102, Australia.
authors.forename: Sahar
authors.initials: S
authors.lastname: Keshvari
authors.affiliation: Cellular and Molecular Metabolism Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, VIC 3004, Australia.
authors.forename: Darren C
authors.initials: DC
authors.lastname: Henstridge
authors.affiliation: University of Queensland, Mater Research Institute-UQ, Brisbane, QLD 4102, Australia.
authors.forename: Choaping
authors.initials: C
authors.lastname: Ng
authors.affiliation: Cellular and Molecular Metabolism Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, VIC 3004, Australia.|Division of Diabetes &Metabolism, Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Febbraio
authors.affiliation: University of Queensland, Mater Research Institute-UQ, Brisbane, QLD 4102, Australia.
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Whitehead
mesh_terms: D052242:Adiponectin / Q000097:blood; D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D059305:Diet, High-Fat; D015870:Gene Expression; D017930:Genes, Reporter; D007249:Inflammation / Q000235:genetics / Q000378:metabolism; D050356:Lipid Metabolism; D051379:Mice; D008820:Mice, Obese; D018482:Muscle, Skeletal / Q000378:metabolism*; D009765:Obesity / Q000209:etiology / Q000378:metabolism; D009928:Organ Specificity; D054419:Receptors, Adiponectin / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D052242:Adiponectin; D054419:Receptors, Adiponectin; C475419:adiponectin receptor 1, mouse; C475421:adiponectin receptor 2, mouse