ARS | Publication request: MALADAPTIVE SKELETAL MUSCLE METABOLISM PRECEDES MALADAPTIVE CHANGES IN CARDIAC METABOLISM AND FUNCTION WITH "WESTERN" DIET IN THE WISTAR RAT

Submitted to: Diabetes
Publication Type: Abstract Only
Publication Acceptance Date: February 1, 2006
Publication Date: June 1, 2006
Citation: Wilson, C.R., Tran, M.K., Guthrie, P.H., King, T.M., Young, M.E., Taegtmeyer, H. 2006. Maladaptive skeletal muscle metabolism precedes maladaptive changes in cardiac metabolism and function with "western" diet in the Wistar rat [abstract]. Diabetes. 55(Suppl.1):A393.

Technical Abstract: Obesity and diabetes are associated with increased fatty acid availability in excess of fatty acid oxidation capacity, which is implicated in the pathogenesis of skeletal muscle insulin resistance and cardiac contractile dysfunction. We tested the hypothesis that a "western" diet induces maladaptation in skeletal muscle metabolism prior to maladaptive changes in cardiac metabolism and function. Male Wistar rats (n=12-17/group) were fed either control or western (10% or 45% calories from fat respectively) diets for short (1-2 months), intermediate (4-6 months), or long (8-12 months) term. In a first set of rats, cardiac power and metabolism were assessed in the isolated working heart. In a parallel set of rats, insulin action was assessed in isolated soleus muscle, while hearts were isolated for mRNA transcript analysis. Soleus muscle oleate oxidation increased with western diet (+60%, p<0.001), but only in the short term. Cardiac oleate oxidation increased with western diet in the short (+36%) and intermediate term (+31%) (p<0.01), but not in the long term. Soleus muscle insulin-mediated glucose oxidation was decreased with western diet in the intermediate term (-59%, p<0.01). Cardiac glucose oxidation was decreased with western diet in the short (-31%), intermediate (-41%) and long term (-39%)(p<0.05) which was coincident with an increase in the mRNA level for pyruvate dehydrogenase kinase 4 in the short (+68%), intermediate (+53%) and long term (+57%)(p<0.01). There was a 24% decrease in cardiac power with western diet in the long term (p<0.05), but not in the short and intermediate term. We conclude impaired insulin action in skeletal muscle precedes metabolic and functional changes in heart muscle when rats are fed a western diet. This supports the concept that early systemic metabolic maladaptation contributes to cardiac metabolic and contractile dysfunction.