First Author | Overstreet AC | Year | 2021 |
Journal | Sci Rep | Volume | 11 |
Issue | 1 | Pages | 9477 |
PubMed ID | 33947892 | Mgi Jnum | J:314413 |
Mgi Id | MGI:6713034 | Doi | 10.1038/s41598-021-88928-8 |
Citation | Overstreet AC, et al. (2021) Gastrokine-1, an anti-amyloidogenic protein secreted by the stomach, regulates diet-induced obesity. Sci Rep 11(1):9477 |
abstractText | Obesity 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. |