title: Skeletal muscle inflammation is not responsible for the rapid impairment in adiponectin response with high-fat feeding in rats.
abstract: Adiponectin (Ad) is an insulin-sensitizing adipokine known to stimulate fatty acid (FA) oxidation in skeletal muscle. Skeletal muscle can become resistant to Ad very rapidly, after only 3 days of high saturated fat feeding in rats. Whether the same occurs following a high polyunsaturated fat diet is unknown. Obesity, insulin resistance, and hyperlipidemia are recognized as low-grade inflammatory diseases; therefore, we hypothesized that high-fat feeding induces inflammation, which interferes with Ad action at skeletal muscle. To this end, rats were placed into one of three dietary groups, control (CON, 10% kcal from fat), high saturated (SAT), or high polyunsaturated (PUFA) fat (60% kcal from fat) for 3 days to determine whether Ad resistance develops. Half of the animals from each group were further supplemented with aspirin, a common anti-inflammatory drug. Ad stimulated FA metabolism, Ad signaling intermediates [AdipoR1, APPL1, LKB1, AMPK, and acetyl-CoA carboxylase (ACC)], and inflammatory proteins [Toll-like receptor (TLR4), IKK alpha/beta, IkappaB alpha, NF-kappaB, suppressor of cytokine signaling-3 (SOCS3), and JNK] were measured in soleus muscle. Three days of SAT feeding induced Ad resistance in soleus muscle, assessed as an inability of Ad to phosphorylate ACC and increase FA oxidation. In PUFA-fed animals, Ad-stimulated FA oxidation and ACC phosphorylation to the same degree as CON animals (FA oxidation: +35%, +41%; pACC +29%, +19%; CON, PUFA, P < 0.05). However, neither SAT nor PUFA feeding for 3 days induced skeletal muscle inflammation. Surprisingly, aspirin prevented Ad-stimulated increases in FA oxidation. In conclusion, FA type is critical in the development of Ad resistance, but this does not appear to be mediated by inflammation.
authors.affiliation: Dept. of Human Health and Nutritional Sciences, Univ. of Guelph, Ontario, Canada, N1G 2W1.
authors.forename: Kerry L
authors.initials: KL
authors.lastname: Mullen
authors.forename: Justine M
authors.initials: JM
authors.lastname: Tishinsky
authors.forename: Lindsay E
authors.initials: LE
authors.lastname: Robinson
authors.forename: David J
authors.initials: DJ
authors.lastname: Dyck
mesh_terms: D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D052242:Adiponectin / Q000378:metabolism*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology; D004041:Dietary Fats / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D005260:Female; D018836:Inflammation Mediators / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D009220:Myositis / Q000209:etiology / Q000378:metabolism* / Q000517:prevention & control; D010084:Oxidation-Reduction; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D052242:Adiponectin; D000894:Anti-Inflammatory Agents, Non-Steroidal; D004041:Dietary Fats; D005227:Fatty Acids; D005231:Fatty Acids, Unsaturated; D018836:Inflammation Mediators; D000103:Acetyl-CoA Carboxylase; D001241:Aspirin