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Metabolic Surgery FaFa rats

ABSTRACT: Gut microbiota contributes to improved glucose tolerance after gastric bypass surgery

PROVIDER: PRJEB58153 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	ERR11144738_1.fastq.gz	Fastqsanger.gz
	ERR11144738_2.fastq.gz	Fastqsanger.gz
	ERR11144739_1.fastq.gz	Fastqsanger.gz
	ERR11144739_2.fastq.gz	Fastqsanger.gz
	ERR11144740_1.fastq.gz	Fastqsanger.gz

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Project description:Gut microbiota contributes to improved glucose tolerance after gastric bypass surgery

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Project description: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.

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Project description:Roux-en-Y gastric bypass (RYGB) is highly effective in reversing obesity and associated diabetes. Recent observations in humans suggest a contributing role of increased circulating bile acids in mediating such effects. Here we use a diet-induced obesity mouse model and compared metabolic remission when bile flow was diverted through a gallbladder anastomosis to jejunum, ileum or duodenum (sham control). We found that only bile diversion to the ileum results in physiologic changes similar to RYGB including sustained improvements in weight, glucose tolerance and hepatic steatosis despite differential effects on hepatic gene expression. Circulating free fatty acids and triglycerides decrease while bile acids increase, particularly conjugated tauro-b-muricholic acid, an FXR antagonist. Activity of the hepatic FXR/FGF15 axis was reduced and associated with altered gut microbiota. Thus bile diversion, independent of surgical rearrangement of the gastrointestinal tract, imparts significant weight loss accompanied by improved glucose and lipid homeostasis that are hallmarks of RYGB. Total RNA from n = 5 DIO, n = 4 GB-IL, n = 5 RYGB mice livers was extracted of total RNA and submitted fro RNAseq

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