Serum bile acids are higher in humans with prior gastric bypass: potential contribution to improved glucose and lipid metabolism.
The multifactorial mechanisms promoting weight loss and improved metabolism following Roux-en-Y gastric bypass (GB) surgery remain incompletely understood. Recent rodent studies suggest that bile acids can mediate energy homeostasis by activating the G-protein coupled receptor TGR5 and the type 2 thyroid hormone deiodinase. Altered gastrointestinal anatomy following GB could affect enterohepatic recirculation of bile acids. We assessed whether circulating bile acid concentrations differ in patients who previously underwent GB, which might then contribute to improved metabolic homeostasis. We performed cross-sectional analysis of fasting serum bile acid composition and both fasting and post-meal metabolic variables, in three subject groups: (i) post-GB surgery (n = 9), (ii) without GB matched to preoperative BMI of the index cohort (n = 5), and (iii) without GB matched to current BMI of the index cohort (n = 10). Total serum bile acid concentrations were higher in GB (8.90 +/- 4.84 micromol/l) than in both overweight (3.59 +/- 1.95, P = 0.005, Ov) and severely obese (3.86 +/- 1.51, P = 0.045, MOb). Bile acid subfractions taurochenodeoxycholic, taurodeoxycholic, glycocholic, glycochenodeoxycholic, and glycodeoxycholic acids were all significantly higher in GB compared to Ov (P < 0.05). Total bile acids were inversely correlated with 2-h post-meal glucose (r = -0.59, P < 0.003) and fasting triglycerides (r = -0.40, P = 0.05), and positively correlated with adiponectin (r = -0.48, P < 0.02) and peak glucagon-like peptide-1 (GLP-1) (r = 0.58, P < 0.003). Total bile acids strongly correlated inversely with thyrotropic hormone (TSH) (r = -0.57, P = 0.004). Together, our data suggest that altered bile acid levels and composition may contribute to improved glucose and lipid metabolism in patients who have had GB.
Harvard Medical School, Harvard University, Boston, Massachusetts, USA. mary.elizabeth.patti@joslin.harvard.edu
Mary-Elizabeth
ME
Patti
Sander M
SM
Houten
Antonio C
AC
Bianco
Raquel
R
Bernier
P Reed
PR
Larsen
Jens J
JJ
Holst
Michael K
MK
Badman
Eleftheria
E
Maratos-Flier
Edward C
EC
Mun
Jussi
J
Pihlajamaki
Johan
J
Auwerx
Allison B
AB
Goldfine
D052242:Adiponectin / Q000097:blood; D000328:Adult; D001647:Bile Acids and Salts / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism*; D015992:Body Mass Index; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D005215:Fasting / Q000097:blood; D005260:Female; D015390:Gastric Bypass; D052216:Glucagon-Like Peptide 1 / Q000097:blood; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000601:surgery*; D019518:Postprandial Period; D012720:Severity of Illness Index; D013972:Thyrotropin / Q000097:blood; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood*; D015854:Up-Regulation
C499918:ADIPOQ protein, human; D052242:Adiponectin; D001647:Bile Acids and Salts; D015415:Biomarkers; D001786:Blood Glucose; D014280:Triglycerides; D052216:Glucagon-Like Peptide 1; D013972:Thyrotropin