title: Increased bile acids in enterohepatic circulation by short-term calorie restriction in male mice.
abstract: 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 "dose-response" 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 "dose-dependently" 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, ω-muricholic acid (ωMCA), and hyodeoxycholic acid. Notably, 40% CR increased TDCA by over 1000% (serum, liver, and gallbladder). Interestingly, 40% CR increased the proportion of 12α-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.
authors.affiliation: Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, Kansas City, KS, 66160, USA.
authors.forename: Zidong Donna
authors.initials: ZD
authors.lastname: Fu
authors.forename: Curtis D
authors.initials: CD
authors.lastname: Klaassen
mesh_terms: D000818:Animals; D001647:Bile Acids and Salts / Q000096:biosynthesis / Q000097:blood*; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D031204:Caloric Restriction; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002790:Cholesterol 7-alpha-Hydroxylase / Q000235:genetics / Q000378:metabolism; D002793:Cholic Acids / Q000097:blood; D003840:Deoxycholic Acid / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004764:Enterohepatic Circulation / Q000187:drug effects*; D006706:Homeostasis; D007422:Intestines / Q000187:drug effects / Q000201:enzymology; D008055:Lipids / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D053719:Tandem Mass Spectrometry
chemical_list: D001647:Bile Acids and Salts; D001786:Blood Glucose; D002352:Carrier Proteins; D002793:Cholic Acids; D008055:Lipids; D012333:RNA, Messenger; D003840:Deoxycholic Acid; C004821:muricholic acid; C010471:hyodeoxycholic acid; D002790:Cholesterol 7-alpha-Hydroxylase; C502772:Cyp7a1 protein, mouse
keywords: 12α-hydroxylated BAs; AL; Asbt; BA; BA profiling; BAL; BAT; Bile acids; Bsep; CA; CDCA; CR; Calorie restriction; DCA; EHC; Enterohepatic circulation; FXR; Fgf; GB; HDCA; Ibabp; LCA; LI; MCA; MDCA; Na(+)/taurocholate cotransporting polypeptide; Ntcp; Oatp; Ost; SHP; SI; T-BA; U-BA; UDCA; UPLC-MS/MS; ad libitum; apical sodium-dependent bile acid transporter; bile acid; bile acid-CoA ligase; bile acid-CoA: amino acid N-acyltransferase; bile salt export pump; calorie restriction; chenodeoxycholic acid; cholic acid; deoxycholic acid; enterohepatic circulation; farnesoid X receptor; fibroblast growth factor; gallbladder; hyodeoxycholic acid; ileal bile acid binding protein; large intestine; lithocholic acid; muricholic acid; murideoxycholic acid; organic anion transporting polypeptide; organic solute transporter; small heterodimer partner; small intestine; taurine-conjugated bile acid; ultra-performance liquid chromatography-tandem mass spectrometry; unconjugated bile acid; ursodeoxycholic acid