title: Functional significance of skeletal muscle adiponectin production, changes in animal models of obesity and diabetes, and regulation by rosiglitazone treatment.
abstract: Endocrine effects of adipose-derived adiponectin on skeletal muscle have been shown to account, at least in part, for the anti-diabetic effects of this adipokine. Recently, the concept of myokines has gained credence, and the potential for skeletal muscle to produce adiponectin has been suggested. Here we demonstrated an increased level of adiponectin mRNA and protein expression as well as protein secretion in response to rosiglitazone treatment in L6 muscle cells. This correlated with the ability of rosiglitazone to enhance insulin sensitivity for stimulation of protein kinase B (Akt) phosphorylation and glucose transport; rosiglitazone also corrected high-glucose-induced insulin resistance in L6 cells. Overexpression of adiponectin confirmed the functional significance of local production of adiponectin in muscle cells via elevated glucose uptake and increased insulin sensitivity. In obese diabetic db/db mice, there was a change in the adiponectin expression profile in soleus and extensor digitorum longus (EDL) muscle with less high molecular weight (HMW) and more medium (MMW)/low (LMW) molecular weight species detected. Induction of obesity and insulin resistance in rats by feeding a high-fat high-sucrose diet also led to decreased muscle HMW adiponectin content that could be corrected by rosiglitazone treatment. In summary, we show the ability of skeletal muscle cells to produce adiponectin, which can mediate autocrine metabolic effects, thus establishing adiponectin as a bona fide myokine. We also demonstrate that skeletal muscle adiponectin production is altered in animal models of obesity and diabetes and that these changes can be corrected by rosiglitazone.
authors.affiliation: Dept. of Biology, York University, Toronto, Ontario, Canada M3J 1P3.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.forename: Simon
authors.initials: S
authors.lastname: Chewchuk
authors.forename: Charles
authors.initials: C
authors.lastname: Lavigne
authors.forename: Sophie
authors.initials: S
authors.lastname: Brûlé
authors.forename: Genevieve
authors.initials: G
authors.lastname: Pilon
authors.forename: Vanessa
authors.initials: V
authors.lastname: Houde
authors.forename: Aimin
authors.initials: A
authors.lastname: Xu
authors.forename: Andre
authors.initials: A
authors.lastname: Marette
authors.forename: Gary
authors.initials: G
authors.lastname: Sweeney
mesh_terms: D052242:Adiponectin / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use; D007328:Insulin / Q000097:blood / Q000494:pharmacology; D008297:Male; D051379:Mice; D008820:Mice, Obese; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D009765:Obesity / Q000097:blood / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D052242:Adiponectin; D007004:Hypoglycemic Agents; D007328:Insulin; D045162:Thiazolidinediones; D000077154:Rosiglitazone