Overstreet, Anne-Marie C.Grayson, Bernadette E.Boger, AntoniaBakke, DanikaCarmody, Erin M.Bales, Cayla E.Paski, Shirley C.Murphy, Stephen F.Dethlefs, Christopher R.Shannon, Kara J.Adlaka, Katie R.Wolford, Claire E.Campiti, Vincent J.Raghunandan, Christina V.Seeley, Randy J.Boone, David L.2022-10-252022-10-252021-05-04Overstreet AC, Grayson BE, Boger A, et al. Gastrokine-1, an anti-amyloidogenic protein secreted by the stomach, regulates diet-induced obesity. Sci Rep. 2021;11(1):9477. Published 2021 May 4. doi:10.1038/s41598-021-88928-8https://hdl.handle.net/1805/30404Obesity and its sequelae have a major impact on human health. The stomach contributes to obesity in ways that extend beyond its role in digestion, including through effects on the microbiome. Gastrokine-1 (GKN1) is an anti-amyloidogenic protein abundantly and specifically secreted into the stomach lumen. We examined whether GKN1 plays a role in the development of obesity and regulation of the gut microbiome. Gkn1−/− mice were resistant to diet-induced obesity and hepatic steatosis (high fat diet (HFD) fat mass (g) = 10.4 ± 3.0 (WT) versus 2.9 ± 2.3 (Gkn1−/−) p < 0.005; HFD liver mass (g) = 1.3 ± 0.11 (WT) versus 1.1 ± 0.07 (Gkn1−/−) p < 0.05). Gkn1−/− mice also exhibited increased expression of the lipid-regulating hormone ANGPTL4 in the small bowel. The microbiome of Gkn1−/− mice exhibited reduced populations of microbes implicated in obesity, namely Firmicutes of the class Erysipelotrichia. Altered metabolism consistent with use of fat as an energy source was evident in Gkn1−/− mice during the sleep period. GKN1 may contribute to the effects of the stomach on the microbiome and obesity. Inhibition of GKN1 may be a means to prevent obesity.en-USAttribution 4.0 InternationalStomachObesityMicrobiomeArticle