| Authors |
McGavigan AK, Garibay D, Henseler ZM, Chen J, Bettaieb A, Haj FG, Ley RE,
Chouinard ML, Cummings BP
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| Submitted By |
Ruth Ley on 11/9/2015 |
| Status |
Published |
| Journal |
Gut |
| Year |
2015 |
| Date Published |
10/1/2015 |
| Volume : Pages |
Not Specified : Not Specified |
| PubMed Reference |
26511794 |
| Abstract |
Vertical sleeve gastrectomy (VSG) produces high rates of type 2 diabetes
remission; however, the mechanisms responsible remain incompletely defined. VSG
increases circulating bile acid concentrations and bile acid signalling through
TGR5 improves glucose homeostasis. Therefore, we investigated the role of TGR5
signalling in mediating the glucoregulatory benefits of VSG., VSG or sham
surgery was performed in high-fat-fed male Tgr5(+/+) (wild type) and Tgr5(-/-)
(knockout) littermates. Sham-operated mice were fed ad libitum or food
restricted to match their body weight to VSG-operated mice. Body weight, food
intake, energy expenditure, insulin signalling and circulating bile acid
profiles were measured and oral glucose tolerance testing, islet
immunohistochemistry and gut microbial profiling were performed., VSG decreased
food intake and body weight, increased energy expenditure and circulating bile
acid concentrations, improved fasting glycaemia, glucose tolerance and
glucose-stimulated insulin secretion, enhanced nutrient-stimulated glucagon-like
peptide 1 secretion and produced favourable shifts in gut microbial populations
in both genotypes. However, the body weight-independent improvements in fasting
glycaemia, glucose tolerance, hepatic insulin signalling, hepatic inflammation
and islet morphology after VSG were attenuated in Tgr5(-/-) relative to
Tgr5(+/+) mice. Furthermore, VSG produced metabolically favourable alterations
in circulating bile acid profiles that were blunted in Tgr5(-/-) relative to
Tgr5(+/+) mice. TGR5-dependent regulation of hepatic Cyp8b1 expression may have
contributed to TGR5-mediated shifts in the circulating bile acid pool after
VSG., These results suggest that TGR5 contributes to the glucoregulatory
benefits of VSG surgery by promoting metabolically favourable shifts in the
circulating bile acid pool.
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