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APPETITE, OBESITY, DIGESTION, AND METABOLISM

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

¹Departments of Medicine and ²Molecular Genetics and Biochemistry, University of Pittsburgh, Pittsburgh, Pennsylvania

Submitted 11 February 2005 ; accepted in final form 1 August 2005

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/IB/NF-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 IB 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 IB 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 IB 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 IB levels in rat skeletal muscle in a fiber-type-dependent manner.

lipids; nuclear factor-B inhibitor kinase; nuclear factor-B inhibitor; nuclear factor-B

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