Diet-induced obesity and acute hyperlipidemia reduce IkappaBalpha 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/IkappaB/NF-kappaB c-Jun NH(2)-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 IkappaBalpha 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 IkappaBalpha 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 IkappaBalpha 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 NH(2)-terminal kinase activity was unchanged by DIO or HL. We conclude that diet-induced obesity and acute HL reduce IkappaBalpha levels in rat skeletal muscle in a fiber-type-dependent manner.
Bhatt
Bankim A
BA
University of Pittsburgh Medical Center, E1112 Biomedical Science Tower, Pittsburgh, PA 15261, USA.
Dube
John J
JJ
Dedousis
Nikolas
N
Reider
Jodie A
JA
O'Doherty
Robert M
RM
D000818:Animals; D004032:Diet; D004655:Emulsions; D005217:Fat Emulsions, Intravenous / Q000008:administration & dosage; D006949:Hyperlipidemias / Q000139:chemically induced* / Q000378:metabolism*; D020672:I-kappa B Proteins / Q000378:metabolism*; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D008297:Male; D018485:Muscle Fibers, Skeletal / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D000072000:NF-KappaB Inhibitor alpha; D009765:Obesity / Q000139:chemically induced* / Q000378:metabolism*; D010743:Phospholipids; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D012450:Safflower Oil; D013024:Soybean Oil; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D004655:Emulsions; D005217:Fat Emulsions, Intravenous; D020672:I-kappa B Proteins; C000606206:Nfkbia protein, rat; D010743:Phospholipids; C063336:safflower oil, soybean oil, phospholipid emulsion; D000072000:NF-KappaB Inhibitor alpha; D013024:Soybean Oil; D012450:Safflower Oil; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4