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FGF19 as a Surgical Factor Contributing to the Metabolic Effects of Gastric Bypass Surgery

ABSTRACT: Gastric bypass surgery has proven to be the most effective treatment in controlling hyperglycemia in severely obese patients with diabetes. Here we show that FGF19, a gut hormone, is rapidly induced by bypass surgery in rodents and humans. Administration of FGF19 achieves remission of diabetes through mechanisms beyond weight loss in animal models of diabetes, supporting a role of FGF19 as part of hormonal changes that influence metabolism following surgery. Through an unbiased phenotypic screen in diabetic mice, we identified selective, safe and effective FGF19 analogues. Unexpectedly, FGF19 analogue failed to correct hyperglycemia in patients with type 2 diabetes. In contrast, administration of FGF19 analogue resulted in rapid, robust and sustained improvement in liver fat content and histology in patients with non-alcoholic steatohepatitis, faithfully replicating effect of the surgery. Thus, our work identifies a strategy of replacing gastric bypass surgery by equally effective, but less invasive, treatment for non-alcoholic steatohepatitis. We used microarrays to detail the global programme of gene expression affected by gastric bypass surgery in rats. Overall design: Rat ileum were selected for RNA extraction and hybridization on Affymetrix microarrays. RNA was isolated from ileum of Zucker fa/fa rats 2 weeks after duodenum-jejunum bypass or sham surgery. RNA integrity and purity were confirmed by Bioanalyzer with RIN numbers > 9.0. Affymetrix rat gene 1.0 ST whole-transcript arrays were used for hybridization.

INSTRUMENT(S): [RaGene-1_0-st] Affymetrix Rat Gene 1.0 ST Array [transcript (gene) version]

ORGANISM(S): Rattus norvegicus  


PROVIDER: GSE120530 | GEO | 2021-09-25


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