Role of Bile Acids and GLP-1 in Mediating the Metabolic Improvements of Bariatric Surgery

Nov 17, 2018Gastroenterology

How Bile Acids and GLP-1 May Help Improve Metabolism After Weight-Loss Surgery

AI simplified

Circadian Biology on OpenScience ↗PubMed ↗DOI ↗

Abstract

Bile diversion to the ileum improves glucose homeostasis by enhancing the intestinal Fxr-GLP-1 axis.

GB-IL led to weight loss and improved glucose tolerance in Tgr5 mice on a high-fat diet, indicating a role for intestinal Fxr.
In wild-type mice on a chow diet, GB-IL resulted in better glycemia and glucose tolerance, independent of weight loss.
Increased lymphatic GLP-1 levels and higher amounts of intestinal Akkermansia muciniphila were observed after GB-IL.
The benefits on fasting glycemia from GB-IL were reduced when a GLP-1 receptor antagonist or a bile acid sequestrant was administered.
The glucoregulatory effects of GB-IL were absent in whole-body Glp-1r mice, highlighting the importance of the GLP-1 pathway.

AI simplified

BACKGROUND & AIMS: Bile diversion to the ileum (GB-IL) has strikingly similar metabolic and satiating effects to Roux-en-Y gastric bypass (RYGB) in rodent obesity models. The metabolic benefits of these procedures are thought to be mediated by increased bile acids, although parallel changes in body weight and other confounding variables limit this interpretation.

METHODS: Global G protein-coupled bile acid receptor-1 null (Tgr5) and intestinal-specific farnesoid X receptor null (Fxr) mice on high-fat diet as well as wild-type C57BL/6 and glucagon-like polypeptide 1 receptor deficient (Glp-1r) mice on chow diet were characterized following GB-IL. -/-Δ/E -/-

RESULTS: GB-IL induced weight loss and improved oral glucose tolerance in Tgr5, but not Fxrmice fed a high-fat diet, suggesting a role for intestinal Fxr. GB-IL in wild-type, chow-fed mice prompted weight-independent improvements in glycemia and glucose tolerance secondary to augmented insulin responsiveness. Improvements were concomitant with increased levels of lymphatic GLP-1 in the fasted state and increased levels of intestinal Akkermansia muciniphila. Improvements in fasting glycemia after GB-IL were mitigated with exendin-9, a GLP-1 receptor antagonist, or cholestyramine, a bile acid sequestrant. The glucoregulatory effects of GB-IL were lost in whole-body Glp-1rmice. -/-Δ/E -/-

CONCLUSIONS: Bile diversion to the ileum improves glucose homeostasis via an intestinal Fxr-Glp-1 axis. Altered intestinal bile acid availability, independent of weight loss, and intestinal Akkermansia muciniphila appear to mediate the metabolic changes observed after bariatric surgery and might be manipulated for treatment of obesity and diabetes.

Full Text

Full text is available at the source.

View full text (XML) ↗View full text ↗

Role of Bile Acids and GLP-1 in Mediating the Metabolic Improvements of Bariatric Surgery

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the circadian biology brief

Abstract

Full Text

Related papers

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the circadian biology brief