Lipolysis in skeletal muscle is decreased in high-fat-fed rats

The intracellular triglyceride content in skeletal muscle is increased in insulin-resistant states such as obesity or high-fat feeding. It has been hypothesized that increased fatty acid oxidation resulting from increased lipolysis of intramyocellular triglycerides may be responsible for this insulin resistance. This study was undertaken to examine whether insulin resistance is associated with increased lipolysis in skeletal muscle in rats fed a high-fat diet. Sprague-Dawley rats were fed a high-fat diet for 5 weeks. Lipolysis in skeletal muscle and adipose tissue was determined by measuring the interstitial glycerol concentrations using a microdialysis method in basal and hyperinsulinemic-euglycemic clamp conditions. In the basal state, plasma free fatty acid (FFA) levels were higher in high-fat-fed rats than in low fat-fed rats (P <.05). In contrast, plasma glycerol levels (P <.001) and interstitial glycerol concentrations of skeletal muscle (P <.05) and adipose tissue (P <.01) were lower in high fat-fed rats than in low fat-fed rats. Plasma (P <.05) and interstitial glycerol concentrations (P <.05 for skeletal muscle, P <.01 for adipose tissue) during the hyperinsulinemic euglycemic clamps were also lower in the high-fat diet group. These results do not support the idea that increased fatty acid oxidation resulting from increased lipolysis of intramyocellular triglycerides is responsible for the insulin resistance in high fat-fed rats.