Increased bile acids in enterohepatic circulation by short-term calorie restriction in male mice

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• 作者：Zidong Donna Fu ; Curtis D. Klaassen
• 关键词：AL ; ad libitum ; Asbt ; apical sodium-dependent bile acid transporter ; BA ; bile acid ; BAL ; bile acid-CoA ligase ; BAT ; bile acid-CoA ; amino acid N-acyltransferase ; Bsep ; bile salt export pump ; CA ; cholic acid ; CDCA ; chenodeoxycholic acid ; CR ; calorie restriction ; DCA ; deoxycholic acid ; EHC ; enterohepatic circulation ; Fgf ; fibroblast growth factor ; FXR ; farnesoid X receptor ; GB ; gallbladder ; HDCA ; hyodeoxycholic acid ; Ibabp ; ileal bile acid binding protein ; LCA ; lithocholic acid ; LI ; large intestine
• 刊名：Toxicology and Applied Pharmacology
• 出版年：15 December, 2013
• 年：2013
• 卷：273
• 期：3
• 页码：680-690
• 全文大小：1865 K

文摘

Previous studies showed glucose and insulin signaling can regulate bile acid (BA) metabolism during fasting or feeding. However, limited knowledge is available on the effect of calorie restriction (CR), a well-known anti-aging intervention, on BA homeostasis. To address this, the present study utilized a 鈥渄ose-response鈥?model of CR, where male C57BL/6 mice were fed 0, 15, 30, or 40% CR diets for one month, followed by BA profiling in various compartments of the enterohepatic circulation by UPLC-MS/MS technique. This study showed that 40% CR increased the BA pool size (162%) as well as total BAs in serum, gallbladder, and small intestinal contents. In addition, CR 鈥渄ose-dependently鈥?increased the concentrations of tauro-cholic acid (TCA) and many secondary BAs (produced by intestinal bacteria) in serum, such as tauro-deoxycholic acid (TDCA), DCA, lithocholic acid, 蠅-muricholic acid (蠅MCA), and hyodeoxycholic acid. Notably, 40% CR increased TDCA by over 1000% (serum, liver, and gallbladder). Interestingly, 40% CR increased the proportion of 12伪-hydroxylated BAs (CA and DCA), which correlated with improved glucose tolerance and lipid parameters. The CR-induced increase in BAs correlated with increased expression of BA-synthetic (Cyp7a1) and conjugating enzymes (BAL), and the ileal BA-binding protein (Ibabp). These results suggest that CR increases BAs in male mice possibly through orchestrated increases in BA synthesis and conjugation in liver as well as intracellular transport in ileum.