title: Effect of Roux-en-Y gastric bypass surgery on bile acid metabolism in normal and obese diabetic rats.
abstract: In addition to classic functions of facilitating hepatobiliary secretion and intestinal absorption of lipophilic nutrients, bile acids (BA) are also endocrine factors and regulate glucose and lipid metabolism. Recent data indicate that antiobesity bariatric procedures e.g. Roux-en-Y gastric bypass surgery (RYGB), which also remit diabetes, increase plasma BAs in humans, leading to the hypothesis that BAs may play a role in diabetes resolution following surgery. To investigate the effect of RYGB on BA physiology and its relationship with glucose homeostasis, we undertook RYGB and SHAM surgery in Zucker diabetic fatty (ZDF) and normoglycemic Sprague Dawley (SD) rats and measured plasma and fecal BA levels, as well as plasma glucose, insulin, Glucagon like peptide 1 (GLP-1) and Peptide YY (PYY), 2 days before and 3, 7, 14 and 28 days after surgery. RYGB decreased body weight and increased plasma GLP-1 in both SD and ZDF rats while decreasing plasma insulin and glucose in ZDF rats starting from the first week. Compared to SHAM groups, both SD-RYGB and ZDF-RYGB groups started to have increases in plasma total BAs in the second week, which might not contribute to early post-surgery metabolic changes. While there was no significant difference in fecal BA excretion between SD-RYGB and SD-SHAM groups, the ZDF-RYGB group had a transient 4.2-fold increase (P<0.001) in 24-hour fecal BA excretion on post-operative day 3 compared to ZDF-SHAM, which paralleled a significant increase in plasma PYY. Ratios of plasma and fecal cholic acid/chenodeoxycholic acid derived BAs were decreased in RYGB groups. In addition, tissue mRNA expression analysis suggested early intestinal BA reabsorption and potentially reduced hepatic cholic acid production in RYGB groups. In summary, we present novel data on RYGB-mediated changes in BA metabolism to further understand the role of BAs in RYGB-induced metabolic effects in humans.
authors: Department of Surgery, Brigham and Women's Hospital, Boston, Massachusetts, United States of America; Harvard Medical School, Boston, Massachusetts, United States of America; Department of Investigative Medicine, Imperial College, London, United Kingdom.
authors: Hina Y
authors: HY
authors: Bhutta
authors: Metabolic Drug Discovery, GlaxoSmithKline Inc., Research Triangle Park, North Carolina, United States of America.
authors: Neetu
authors: N
authors: Rajpal
authors: Molecular Discovery Research, GlaxoSmithKline Inc., Research Triangle Park, North Carolina, United States of America.
authors: Wendy
authors: W
authors: White
authors: Quantitative Sciences Division, GlaxoSmithKline Inc., Research Triangle Park, North Carolina, United States of America.
authors: Johannes M
authors: JM
authors: Freudenberg
authors: Metabolic Drug Discovery, GlaxoSmithKline Inc., Research Triangle Park, North Carolina, United States of America.
authors: Yaping
authors: Y
authors: Liu
authors: Metabolic Drug Discovery, GlaxoSmithKline Inc., Research Triangle Park, North Carolina, United States of America.
authors: James
authors: J
authors: Way
authors: Quantitative Sciences Division, GlaxoSmithKline Inc., Research Triangle Park, North Carolina, United States of America.
authors: Deepak
authors: D
authors: Rajpal
authors: Quantitative Sciences Division, GlaxoSmithKline Inc., Research Triangle Park, North Carolina, United States of America.
authors: David C
authors: DC
authors: Cooper
authors: Metabolic Drug Discovery, GlaxoSmithKline Inc., Research Triangle Park, North Carolina, United States of America.
authors: Andrew
authors: A
authors: Young
authors: Department of Surgery, Brigham and Women's Hospital, Boston, Massachusetts, United States of America; Harvard Medical School, Boston, Massachusetts, United States of America.
authors: Ali
authors: A
authors: Tavakkoli
authors: Metabolic Drug Discovery, GlaxoSmithKline Inc., Research Triangle Park, North Carolina, United States of America.
authors: Lihong
authors: L
authors: Chen
mesh_terms: D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism*; D001786:Blood Glucose; D001835:Body Weight; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000378:metabolism* / Q000601:surgery*; D004195:Disease Models, Animal; D015390:Gastric Bypass / Q000379:methods; D005749:Gastric Inhibitory Polypeptide / Q000097:blood; D020869:Gene Expression Profiling; D052216:Glucagon-Like Peptide 1 / Q000097:blood; D007328:Insulin / Q000097:blood; D009928:Organ Specificity / Q000235:genetics; D019894:Peptide YY / Q000097:blood; D051381:Rats
chemical_list: D001647:Bile Acids and Salts; D001786:Blood Glucose; D007328:Insulin; D019894:Peptide YY; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1