Submitted to: Diabetes
Publication Type: Abstract Only
Publication Acceptance Date: 3/12/2008
Publication Date: 6/10/2008
Citation: Qin, B., Khosrowl, A., Anderson, R.A. 2008. Tumor Necrosis Factor-alpha Stimulates the Overproduction of Intestinal Apolipoprotein B48-containing Very Low Density Lipoproproteins. Diabetes. 888:102. Interpretive Summary:
Technical Abstract: Tumor necrosis factor-alpha(a)(TNFa), a proinflammatory cytokine, is involved in obesity-associated pathologies including type 2 diabetes and atherosclerosis. TNFa enhanced postprandial apoB48-VLDL1 overproduction by about 89% compared with the control after 90 min olive oil loading; TNFa did not significantly affect apoB-48 VLDL2 expression. In addition, acute oral treatment of Cinnulin PF (a water soluble cinnamon extract, 50 mg per kg BW), which has insulin-like metabolic actions, inhibits TNFa-induced postprandial overproduction of apoB48-containing lipoproteins. Fresh isolated primary enterocytes of hamsters were stimulated with TNFa (10 ng per mL for 4hs), to investigate the expression of insulin signaling pathway genes, insulin receptor (IR), IRS1, IRS2, Akt1, and phosphatidylinositol3-kinase (PI3K), and the key regulators of lipid metabolism, microsomal triglyceride transfer protein(MTP), sterol regulatory element-binding protein (SREBP)1c, and phosphatase and tensin homology (PTEN), as well as the inflammatory factor genes, ILa, ILBeta, IL6, and TNFa. Quantitative real-time PCR assays showed that TNFa decreased IR, IRS1, IRS2, PI3K and Akt1 mRNA levels of enterocytes by 45, 59, 60, 59, and 38%, respectively, of controls. In summary, TNFa stimulates the postprandial apoB-48 VLDL1 overproduction via regulation of mRNA levels of proteins in the intestinal insulin signaling pathway, and perturbs the expression of MTP, PTEN, and SREBP1c, as well as enhances the expression of inflammation factors. Taken together with previous studies, the improvement of insulin sensitivity will inhibit the overproduction of apoB48-containing lipoproteins induced by factors and diets that increase TNFa levels.