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Am J Physiol Regul Integr Comp Physiol (August 4, 2005). doi:10.1152/ajpregu.00097.2005
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Submitted on February 11, 2005
Accepted on August 1, 2005

Diet-Induced Obesity and Acute Hyperlipidemia Reduce I{kappa}B{alpha} Levels in Rat Skeletal Muscle in a Fiber-Type Dependent Manner

Bankim A Bhatt1, John J Dube1, Nikolas Dedousis1, Jodie A Reider1, and Robert M O'Doherty2*

1 Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA
2 Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA; Department of Molecular Genetics and Biochemistry, University of Pittsburgh, Pittsburgh, PA, USA

* To whom correspondence should be addressed. E-mail: odohertyr{at}dom.pitt.edu.

Increased activity of pro-inflammatory/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 pro-inflammatory/stress pathways in obesity are unknown. The current study addressed in rats the effects of diet-induced obesity (DIO, 6 weeks of high fat feeding) and acute (6h) hyperlipidemia (HL) on activity of IKK/I{kappa}B/NF{kappa}B, JNK, 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 NF{kappa}B inhibitor, I{kappa}B{alpha}, in VAS (24±3%, P=0.001, n=8) but not in SOL or GAS compared to 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 to 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 JNK activity was unchanged by DIO or HL. We conclude that diet-induced obesity and acute hyperlipidemia reduce I{kappa}B{alpha} levels in rat skeletal muscle in a fiber-type dependent manner.




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