Diet-induced modulation of mitochondrial activity in rat muscle

Abstract

doi:10.1152/ajpendo.00263.2007.—Growing evidence supports the theory that mitochondrial dysfunction is an underlying cause of intramyocellular lipid (IMCL) accumulation and insulin resistance. Here, we hypothesized that high dietary fat (HF) intake could trigger changes in mitochondrial activity such that fatty acid oxidation is impaired in muscle and contributes to an elevation in intramyocellular lipid (IMCL) levels. Muscle mitochondrial activity was determined in vivo through measurement of the F1F0 ATP synthase flux, the terminal step in the oxidative phosphorylation process. An initial study comparing rats on normal chow diet with rats on an HF diet revealed strong correlations between muscle ATP synthesis rates, IMCL levels and whole body glucose tolerance. Results obtained from two latter studies showed multiphasic responses to dietary interven-tion. Initially, the ATP synthesis rates decreased as much as 50% within 24 h of raising the fat content in the diet to 60 % of the calori