RNA-Seq Analysis of Enteroendocrine Cells Reveals a Role for FABP5 in the Control of GIP Secretion

In response to fat intake, enteroendocrine K cells release the hormone glucose-dependent insulinotropic polypeptide (GIP). GIP acts on adipocytes to increase lipid uptake and enhance adipokine secretion, promoting weight gain and insulin resistance. Modulation of intestinal GIP release could therefore represent a therapeutic strategy for the treatment and prevention of obesity and diabetes. However, the prospects of using drugs to effectively target specific enteroendocrine cell types have been tempered by the realization that these cells share similar transcriptional programs and frequently employ common mechanisms of hormone secretion. To gain novel insights into the regulation of GIP release, we generated knock-in mice expressing green fluorescent protein (GFP) under the control of the endogenous GIP promoter that enable the isolation of a purified population of small intestine K cells. Using RNA sequencing, we comprehensively characterized the transcriptomes of GIPGFP cells as well as the entire enter...