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ARS Home » Northeast Area » Beltsville, Maryland (BHNRC) » Beltsville Human Nutrition Research Center » Diet, Genomics and Immunology Laboratory » Research » Publications at this Location » Publication #207427
Title: Tumor necrosis factor-alpha impairs hepatic insulin signaling and stumlates the overproduction of hepatic apolipoprotein B100-containing very low density lipoproteins

Author
item QIN, BOLIN - INTEGRITY NEUTRCEUTICALS,
item Anderson, Richard
item ADELI, KHOSROW - U OF TORONTO, CANADA

Submitted to: American Diabetes Association Meeting
Publication Type: Abstract Only
Publication Acceptance Date: 4/18/2007
Publication Date: 6/18/2007
Citation: Qin, B., Anderson, R.A., Adeli, K. 2007. Tumor necrosis factor-alpha impairs hepatic insulin signaling and stumlates the overproduction of hepatic apolipoprotein B100-containing very low density lipoproteins. American Diabetes Association Meeting. Publication Number 0216-OR.

Interpretive Summary:

Technical Abstract: Mechanisms underlying hepatic overproduction of apolipoprotein B (apoB) 100-containing very low density lipoproteins (VLDL) in insulin resistance induced by tumor necrosis factor (TNF)-a were investigated. In the present study, we examined the potential role of TNF-a in insulin signaling and lipoprotein metabolism in the liver of Syrian golden hamsters. In vivo TNF-a infusion induced whole-body insulin resistance in chow-fed hamsters. Analysis of liver in TNF-a-treated hamsters indicated decreased phosphorylation of insulin receptor (IR)-b, IR substrate (IRS)-1 (Tyr), Akt (ser473), p38, ERK1/2, and JNK, but increased phosphorylation of ser307 IRS-1 and Shc. TNF-a infusion also significantly increased hepatic production of total serum and VLDL-apoB100 in both fasting and postprandial (fat load) states. Ex vivo experiments, using cultured primary hepatocytes from hamsters, also showed TNF-a-induced VLDL-apoB100 oversecretion, an effect that was blocked by TNF receptor 2 antibody. Moreover, TNF-a decreased the sterol regulatory element binding protein-1c mRNA and increased microsomal triglyceride transfer protein mRNA without altering apoB mRNA levels in primary hepatocytes. In summary, we provide direct evidence that TNF-a impairs hepatic insulin signaling in hamsters accompanied by hepatic overproduction of apoB100-containing VLDL particles, effect likely mediated via TNF receptor 2.