Diet-induced obesity and acute hyperlipidemia reduce IαBα levels in rat skeletal muscle in a fiber-type dependent manner

Increased activity of proinflammatory/stress pathways has been implicated in the pathogenesis of insulin resistance in obesity. However, the effects of obesity on the activity of these pathways in skeletal muscle, the major insulin-sensitive tissue by mass, are poorly understood. Furthermore, the mechanisms that activate proinflammatory/stress pathways in obesity are unknown. The present study addressed the effects of diet-induced obesity (DIO; 6 wk of high-fat feeding) and acute (6-h) hyperlipidemia (HL) in rats on activity of IKK/I kappa B/NF-kappa B c-Jun NH2-terminal kinase, and p38 MAPK in three skeletal muscles differing in fiber type [ superficial vastus ( Vas; fast twitch-glycolytic), soleus ( Sol; slow twitch-oxidative), and gastrocnemius ( Gas; mixed)]. DIO decreased the levels of the I kappa B alpha in Vas ( 24 +/- 3%, P = 0.001, n = 8) but not in Sol or Gas compared with standard chow-fed controls. Similar to DIO, HL decreased I kappa B alpha levels in Vas ( 26 +/- 5%, P = 0.006, n = 6) and in Gas ( 15 +/- 4%, P = 0.01, n = 7) but not in Sol compared with saline-infused controls. Importantly, the fiber-type-dependent effects on I kappa B alpha levels could not be explained by differential accumulation of triglyceride in Sol and Vas. HL, but not DIO, decreased phospho-p38 MAPK levels in Vas ( 41 +/- 7% P = 0.004, n = 6) but not in Sol or Gas. Finally, skeletal muscle c-Jun NH2-terminal kinase activity was unchanged by DIO or HL. We conclude that diet-induced obesity and acute HL reduce I kappa B alpha levels in rat skeletal muscle in a fiber-type-dependent manner.