Submitted to: Hormone and Metabolic Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/27/2009
Publication Date: 4/27/2009
Citation: Qin, B., Dawson, H.D., Polansky, M.M., Anderson, R.A. 2009. Cinnamon extract attenuates TNF-alpha-induced Intestinal lipoprotein ApoB48 overproduction by regulating inflammatory, insulin and lipoprotein pathways in enterocytes. Hormone and Metabolic Research. 41:1-7.
Interpretive Summary: Factors that are associated with inflammation, such as tumor necrosis factor (TNF-a), are present at increased concentrations in individuals who are insulin resistant and obese, and increases in inflammatory biomarkers are associated with the development of type 2 diabetes and cardiovascular disease. In the current study, we evaluated whether a water extract of cinnamon (CE = Cinnulin PF®) improved abnormal blood lipids (dyslipidemia) and reduced inflammatory pathways. CE fed to hamsters inhibited TNF-a-induced overproduction of triglycerides and fat binding proteins that are associated with higher risk of cardiovascular disease. CE also reversed the negative effects of TNF-a on genes involving inflammatory, insulin, and lipoproteins. In conclusion, a water extract of cinnamon improved inflammation markers related to impaired fat metabolism. This study will be of benefit to scientists working on the mechanism of cardiovascular diseases associated with insulin resistance and potentially to the millions of people with diabetes and cardiovascular diseases.
Technical Abstract: We evaluated whether a water extract of cinnamon (CE = Cinnulin PF®) attenuates the dyslipidemia induced by TNF-alpha in Triton WR-1339-treated hamsters, and whether CE inhibited the over-secretion of apoB48-induced by TNF-alpha in enterocytes in a 35S-labelling study. In vivo, oral treatment with CE (50 mg per kg BW), inhibited the postprandial overproduction of apoB48-containing lipoproteins and serum triglyceride levels. In ex vivo 35S-labeling studies, CE (10 and 20 µg/mL) inhibited the oversecretion of apoB48 induced by TNF-alpha-treated enterocytes into the media. To determine the molecular mechanisms, isolated primary enterocytes of hamsters were pre-treated with TNF-alpha and then treated with and without CE (10 µ/mL) for 0.5, 2, and 4h, and the expression of the inflammatory genes, IL1-beta, IL-6, and TNF-alpha; insulin signaling pathways genes insulin receptor (IR), IRS1, IRS2, phosphatidylinositol 3-kinase (PI3-K), and Akt1; and phosphatase and tensin homology (PTEN) as well as the key regulators of lipid metabolism cluster of differentiation (CD)36, microsomal triglyceride transfer protein (MTTP), and sterol regulatory element binding protein (SREBP)-1c were evaluated. Quantitative real-time PCR assays showed that CE treatment decreased the mRNA expression of IL-beta, IL-6, and TNF-alpha; improved the mRNA expression of IR, IRS1, IRS2, PI3K and Akt1; inhibited CD36, MTTP, and PTEN; and enhanced the impaired SREBP-1c expression in TNF-alpha treated enterocytes. These data demonstrate that a water extract of cinnamon reversed TNF-alpha-induced overproduction of intestinal apoB48 by regulating the gene expression involved in inflammatory, insulin, and lipoprotein signaling pathways.