Gastrokine-1, an anti-amyloidogenic protein secreted by the stomach, regulates diet-induced obesity

Abstract 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...

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Autores principales:	Anne-Marie C. Overstreet, Bernadette E. Grayson, Antonia Boger, Danika Bakke, Erin M. Carmody, Cayla E. Bales, Shirley C. Paski, Stephen F. Murphy, Christopher R. Dethlefs, Kara J. Shannon, Katie R. Adlaka, Claire E. Wolford, Vincent J. Campiti, Christina V. Raghunandan, Randy J. Seeley, David L. Boone
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e0898e43e9d842fda58154164588cbbb
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spelling	oai:doaj.org-article:e0898e43e9d842fda58154164588cbbb2021-12-02T14:29:09ZGastrokine-1, an anti-amyloidogenic protein secreted by the stomach, regulates diet-induced obesity10.1038/s41598-021-88928-82045-2322https://doaj.org/article/e0898e43e9d842fda58154164588cbbb2021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-88928-8https://doaj.org/toc/2045-2322Abstract 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.Anne-Marie C. OverstreetBernadette E. GraysonAntonia BogerDanika BakkeErin M. CarmodyCayla E. BalesShirley C. PaskiStephen F. MurphyChristopher R. DethlefsKara J. ShannonKatie R. AdlakaClaire E. WolfordVincent J. CampitiChristina V. RaghunandanRandy J. SeeleyDavid L. BooneNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Anne-Marie C. Overstreet Bernadette E. Grayson Antonia Boger Danika Bakke Erin M. Carmody Cayla E. Bales Shirley C. Paski Stephen F. Murphy Christopher R. Dethlefs Kara J. Shannon Katie R. Adlaka Claire E. Wolford Vincent J. Campiti Christina V. Raghunandan Randy J. Seeley David L. Boone Gastrokine-1, an anti-amyloidogenic protein secreted by the stomach, regulates diet-induced obesity
description	Abstract 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.
format	article
author	Anne-Marie C. Overstreet Bernadette E. Grayson Antonia Boger Danika Bakke Erin M. Carmody Cayla E. Bales Shirley C. Paski Stephen F. Murphy Christopher R. Dethlefs Kara J. Shannon Katie R. Adlaka Claire E. Wolford Vincent J. Campiti Christina V. Raghunandan Randy J. Seeley David L. Boone
author_facet	Anne-Marie C. Overstreet Bernadette E. Grayson Antonia Boger Danika Bakke Erin M. Carmody Cayla E. Bales Shirley C. Paski Stephen F. Murphy Christopher R. Dethlefs Kara J. Shannon Katie R. Adlaka Claire E. Wolford Vincent J. Campiti Christina V. Raghunandan Randy J. Seeley David L. Boone
author_sort	Anne-Marie C. Overstreet
title	Gastrokine-1, an anti-amyloidogenic protein secreted by the stomach, regulates diet-induced obesity
title_short	Gastrokine-1, an anti-amyloidogenic protein secreted by the stomach, regulates diet-induced obesity
title_full	Gastrokine-1, an anti-amyloidogenic protein secreted by the stomach, regulates diet-induced obesity
title_fullStr	Gastrokine-1, an anti-amyloidogenic protein secreted by the stomach, regulates diet-induced obesity
title_full_unstemmed	Gastrokine-1, an anti-amyloidogenic protein secreted by the stomach, regulates diet-induced obesity
title_sort	gastrokine-1, an anti-amyloidogenic protein secreted by the stomach, regulates diet-induced obesity
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/e0898e43e9d842fda58154164588cbbb
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Gastrokine-1, an anti-amyloidogenic protein secreted by the stomach, regulates diet-induced obesity

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