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...
| Main Authors: | , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2021-05-01
|
| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-88928-8 |
| _version_ | 1818857813636546560 |
|---|---|
| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-19T08:46:22Z |
| format | Article |
| id | doaj.art-e0898e43e9d842fda58154164588cbbb |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-19T08:46:22Z |
| publishDate | 2021-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-e0898e43e9d842fda58154164588cbbb2022-12-21T20:28:50ZengNature PortfolioScientific Reports2045-23222021-05-0111111310.1038/s41598-021-88928-8Gastrokine-1, an anti-amyloidogenic protein secreted by the stomach, regulates diet-induced obesityAnne-Marie C. Overstreet0Bernadette E. Grayson1Antonia Boger2Danika Bakke3Erin M. Carmody4Cayla E. Bales5Shirley C. Paski6Stephen F. Murphy7Christopher R. Dethlefs8Kara J. Shannon9Katie R. Adlaka10Claire E. Wolford11Vincent J. Campiti12Christina V. Raghunandan13Randy J. Seeley14David L. Boone15Department of Microbiology and Immunology, Indiana University School of Medicine-South BendDivision of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, University of CincinnatiDepartment of Microbiology and Immunology, Indiana University School of Medicine-South BendDepartment of Microbiology and Immunology, Indiana University School of Medicine-South BendDepartment of Biology, University of Notre DameDepartment of Biology, University of Notre DameCedars-Sinai Medical CenterDepartment of Urology, Feinberg School of Medicine, Northwestern UniversityDepartment of Biology, University of Notre DameDepartment of Biology, University of Notre DameDepartment of Biology, University of Notre DameDepartment of Biology, University of Notre DameDepartment of Microbiology and Immunology, Indiana University School of Medicine-South BendDepartment of Microbiology and Immunology, Indiana University School of Medicine-South BendDivision of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, University of CincinnatiDepartment of Microbiology and Immunology, Indiana University School of Medicine-South BendAbstract 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.https://doi.org/10.1038/s41598-021-88928-8 |
| spellingShingle | 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 Scientific Reports |
| title | 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_short | 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 |
| url | https://doi.org/10.1038/s41598-021-88928-8 |
| work_keys_str_mv | AT annemariecoverstreet gastrokine1anantiamyloidogenicproteinsecretedbythestomachregulatesdietinducedobesity AT bernadetteegrayson gastrokine1anantiamyloidogenicproteinsecretedbythestomachregulatesdietinducedobesity AT antoniaboger gastrokine1anantiamyloidogenicproteinsecretedbythestomachregulatesdietinducedobesity AT danikabakke gastrokine1anantiamyloidogenicproteinsecretedbythestomachregulatesdietinducedobesity AT erinmcarmody gastrokine1anantiamyloidogenicproteinsecretedbythestomachregulatesdietinducedobesity AT caylaebales gastrokine1anantiamyloidogenicproteinsecretedbythestomachregulatesdietinducedobesity AT shirleycpaski gastrokine1anantiamyloidogenicproteinsecretedbythestomachregulatesdietinducedobesity AT stephenfmurphy gastrokine1anantiamyloidogenicproteinsecretedbythestomachregulatesdietinducedobesity AT christopherrdethlefs gastrokine1anantiamyloidogenicproteinsecretedbythestomachregulatesdietinducedobesity AT karajshannon gastrokine1anantiamyloidogenicproteinsecretedbythestomachregulatesdietinducedobesity AT katieradlaka gastrokine1anantiamyloidogenicproteinsecretedbythestomachregulatesdietinducedobesity AT claireewolford gastrokine1anantiamyloidogenicproteinsecretedbythestomachregulatesdietinducedobesity AT vincentjcampiti gastrokine1anantiamyloidogenicproteinsecretedbythestomachregulatesdietinducedobesity AT christinavraghunandan gastrokine1anantiamyloidogenicproteinsecretedbythestomachregulatesdietinducedobesity AT randyjseeley gastrokine1anantiamyloidogenicproteinsecretedbythestomachregulatesdietinducedobesity AT davidlboone gastrokine1anantiamyloidogenicproteinsecretedbythestomachregulatesdietinducedobesity |