Cinnamon extract attenuates TNF-alpha-induced intestinal lipoprotein ApoB48 overproduction by regulating inflammatory, insulin, and lipoprotein pathways in enterocytes.

We have previously reported that the obesity-associated proinflammatory cytokine, TNF-alpha, stimulates the overproduction of intestinal apolipoprotein (apo) B48 containing lipoproteins. In the current study, we have evaluated whether a water-soluble cinnamon extract [CE (Cinnulin PF)] attenuates the dyslipidemia induced by TNF-alpha in Triton WR-1339 treated hamsters, and whether CE inhibits the oversecrection of apoB48-induced by TNF-alpha in enterocytes in a 35S labeling study. In vivo, oral treatment of Cinnulin PF (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 microg/ml) inhibited the oversecretion of apoB48 induced by TNF-alpha treated enterocytes into the media. To determine the molecular mechanisms, TNF-alpha treated primary enterocytes isolated from chow-fed hamsters, were incubated with CE (10 microg/ml), and the expression of the inflammatory factor genes, IL1-beta, IL-6, and TNF-alpha, insulin signaling pathway genes, insulin receptor (IR), IRS1, IRS2, phosphatidylinositol 3-kinase (PI3-K), 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-1beta, 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 suggest that a water extract of cinnamon reverses TNF-alpha-induced overproduction of intestinal apoB48 by regulating gene expression involving inflammatory, insulin, and lipoprotein signaling pathways. In conclusion, Cinulin PF improves inflammation related intestinal dyslipidemia.