G-protein coupled receptor 19 (GPR19) knockout mice display sex-dependent metabolic dysfunction
Abstract G-protein coupled receptors (GPCRs) mediate signal transduction from the cellular surface to intracellular metabolic pathways. While the function of many GPCRs has been delineated previously, a significant number require further characterization to elucidate their cellular function. G-prote...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-04-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-33308-7 |
| _version_ | 1797845966414413824 |
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| author | Bellina A. S. Mushala Bingxian Xie Ian J. Sipula Michael W. Stoner Dharendra Thapa Janet R. Manning Paramesha Bugga Amber M. Vandevender Michael J. Jurczak Iain Scott |
| author_facet | Bellina A. S. Mushala Bingxian Xie Ian J. Sipula Michael W. Stoner Dharendra Thapa Janet R. Manning Paramesha Bugga Amber M. Vandevender Michael J. Jurczak Iain Scott |
| author_sort | Bellina A. S. Mushala |
| collection | DOAJ |
| description | Abstract G-protein coupled receptors (GPCRs) mediate signal transduction from the cellular surface to intracellular metabolic pathways. While the function of many GPCRs has been delineated previously, a significant number require further characterization to elucidate their cellular function. G-protein coupled receptor 19 (GPR19) is a poorly characterized class A GPCR which has been implicated in the regulation of circadian rhythm, tumor metastasis, and mitochondrial homeostasis. In this report, we use a novel knockout (KO) mouse model to examine the role of GPR19 in whole-body metabolic regulation. We show that loss of GPR19 promotes increased energy expenditure and decreased activity in both male and female mice. However, only male GPR19 KO mice display glucose intolerance in response to a high fat diet. Loss of GPR19 expression in male mice, but not female mice, resulted in diet-induced hepatomegaly, which was associated with decreased expression of key fatty acid oxidation genes in male GPR19 KO livers. Overall, our data suggest that loss of GPR19 impacts whole-body energy metabolism in diet-induced obese mice in a sex-dependent manner. |
| first_indexed | 2024-04-09T17:47:29Z |
| format | Article |
| id | doaj.art-c29485daa80649a8ab8c95d978674e6e |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-09T17:47:29Z |
| publishDate | 2023-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-c29485daa80649a8ab8c95d978674e6e2023-04-16T11:15:09ZengNature PortfolioScientific Reports2045-23222023-04-0113111010.1038/s41598-023-33308-7G-protein coupled receptor 19 (GPR19) knockout mice display sex-dependent metabolic dysfunctionBellina A. S. Mushala0Bingxian Xie1Ian J. Sipula2Michael W. Stoner3Dharendra Thapa4Janet R. Manning5Paramesha Bugga6Amber M. Vandevender7Michael J. Jurczak8Iain Scott9Vascular Medicine Institute, Department of Medicine, University of PittsburghCenter for Metabolism and Mitochondrial Medicine, Department of Medicine, University of PittsburghCenter for Metabolism and Mitochondrial Medicine, Department of Medicine, University of PittsburghVascular Medicine Institute, Department of Medicine, University of PittsburghVascular Medicine Institute, Department of Medicine, University of PittsburghVascular Medicine Institute, Department of Medicine, University of PittsburghVascular Medicine Institute, Department of Medicine, University of PittsburghVascular Medicine Institute, Department of Medicine, University of PittsburghVascular Medicine Institute, Department of Medicine, University of PittsburghVascular Medicine Institute, Department of Medicine, University of PittsburghAbstract G-protein coupled receptors (GPCRs) mediate signal transduction from the cellular surface to intracellular metabolic pathways. While the function of many GPCRs has been delineated previously, a significant number require further characterization to elucidate their cellular function. G-protein coupled receptor 19 (GPR19) is a poorly characterized class A GPCR which has been implicated in the regulation of circadian rhythm, tumor metastasis, and mitochondrial homeostasis. In this report, we use a novel knockout (KO) mouse model to examine the role of GPR19 in whole-body metabolic regulation. We show that loss of GPR19 promotes increased energy expenditure and decreased activity in both male and female mice. However, only male GPR19 KO mice display glucose intolerance in response to a high fat diet. Loss of GPR19 expression in male mice, but not female mice, resulted in diet-induced hepatomegaly, which was associated with decreased expression of key fatty acid oxidation genes in male GPR19 KO livers. Overall, our data suggest that loss of GPR19 impacts whole-body energy metabolism in diet-induced obese mice in a sex-dependent manner.https://doi.org/10.1038/s41598-023-33308-7 |
| spellingShingle | Bellina A. S. Mushala Bingxian Xie Ian J. Sipula Michael W. Stoner Dharendra Thapa Janet R. Manning Paramesha Bugga Amber M. Vandevender Michael J. Jurczak Iain Scott G-protein coupled receptor 19 (GPR19) knockout mice display sex-dependent metabolic dysfunction Scientific Reports |
| title | G-protein coupled receptor 19 (GPR19) knockout mice display sex-dependent metabolic dysfunction |
| title_full | G-protein coupled receptor 19 (GPR19) knockout mice display sex-dependent metabolic dysfunction |
| title_fullStr | G-protein coupled receptor 19 (GPR19) knockout mice display sex-dependent metabolic dysfunction |
| title_full_unstemmed | G-protein coupled receptor 19 (GPR19) knockout mice display sex-dependent metabolic dysfunction |
| title_short | G-protein coupled receptor 19 (GPR19) knockout mice display sex-dependent metabolic dysfunction |
| title_sort | g protein coupled receptor 19 gpr19 knockout mice display sex dependent metabolic dysfunction |
| url | https://doi.org/10.1038/s41598-023-33308-7 |
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