High-fat-induced intestinal permeability dysfunction associated with altered fecal bile acids

作者：Stenman Lotta K^*; Holma Reetta; Korpela Riitta

来源：World Journal of Gastroenterology, 2012, 18(9): 923-929.

DOI：10.3748/wjg.v18.i9.923

• Bile acids
• Bile salts
• Diet-induced obesity
• Farnesoid X-activated receptor
• Intestinal permeability
• Ursodeoxycholic acid

AIM: To investigate whether high-fat-feeding is associated with increased intestinal permeability via alterations in bile acid metabolism. %26lt;br%26gt;METHODS: Male C57BI/63 mice were fed on a high-fat (n = 26) or low-fat diet (n = 24) for 15 wk. Intestinal permeability was measured from duodenum, jejunum, ileum and colon in an Ussing chamber system using 4 kDa FITC-labeled dextran as an indicator. Fecal bile acids were analyzed with gas chromatography. Segments of jejunum and colon were analyzed for the expression of farnesoid X receptor (FXR) and tumor necrosis factor (TNF). %26lt;br%26gt;RESULTS: Intestinal permeability was significantly increased by high-fat feeding in jejunum (median 0.334 for control vs 0.393 for high-fat, P = 0.03) and colon (0.335 for control vs 0.433 for high-fat, P = 0.01), but not in duodenum or ileum. The concentration of nearly all identified bile acids was significantly increased by high-fat feeding (P %26lt; 0.001). The proportion of ursodeoxycholic acid (UDCA) in all bile acids was decreased (1.4% +/- 0.1% in high-fat vs 2.8% +/- 0.3% in controls, P %26lt; 0.01) and correlated inversely with intestinal permeability (r = -0.72, P = 0.01). High-fat feeding also increased jejuna! FXR expression, as well as TNF expression along the intestine, especially in the colon. %26lt;br%26gt;CONCLUSION: High-fat-feeding increased intestinal permeability, perhaps by a mechanism related to bile acid metabolism, namely a decreased proportion of fecal UDCA and increased FXR expression.

• 出版日期2012-3-7