Short‐term dietary methionine restriction with high fat diet counteracts metabolic dysfunction in male mice
Abstract Dietary methionine restriction (MetR) promotes metabolic health, and we tested the impact of short durations of MetR on high fat diet (HFD)‐induced metabolic dysfunction with the maintenance of HFD. Male C57BL/6J mice were fed HFD from 10 to 25 weeks of age, then maintained on HFD or fed HF...
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| Format: | Article |
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Wiley
2025-06-01
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| Series: | Physiological Reports |
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| Online Access: | https://doi.org/10.14814/phy2.70405 |
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| author | Marissa I. McGilvrey Bethany Fortier Diana Cooke Maryam A. Mahdi Benjamin Tero Christian M. Potts Abigail Kaija Larisa Ryzhova Carolina Cora Adam Richardson Douglas Guzior Ilka Pinz Calvin Vary Robert A. Koza Gene Ables Lucy Liaw |
| author_facet | Marissa I. McGilvrey Bethany Fortier Diana Cooke Maryam A. Mahdi Benjamin Tero Christian M. Potts Abigail Kaija Larisa Ryzhova Carolina Cora Adam Richardson Douglas Guzior Ilka Pinz Calvin Vary Robert A. Koza Gene Ables Lucy Liaw |
| author_sort | Marissa I. McGilvrey |
| collection | DOAJ |
| description | Abstract Dietary methionine restriction (MetR) promotes metabolic health, and we tested the impact of short durations of MetR on high fat diet (HFD)‐induced metabolic dysfunction with the maintenance of HFD. Male C57BL/6J mice were fed HFD from 10 to 25 weeks of age, then maintained on HFD or fed HFD with 80% reduced methionine (HFD‐MetR) for 3, 5, or 10 days. Blood, liver, adipose tissue, and aortae underwent phenotypic assessment, proteomics, and metabolomics. HFD‐MetR induced rapid weight loss and robust metabolic improvement within 10 days. Significant reductions in body weight, circulating triglycerides, glucose, insulin, adipokines and hepatokines reflected metabolic health. Proteomics revealed enriched metabolic signatures in perivascular adipose tissue (PVAT) and structural remodeling signatures in aorta. Metabolomics identified a cardioprotective signature in blood plasma, and activated mitochondrial activity and energy production in liver and brown adipose tissue. HFD‐MetR reversed metabolic dysfunction, and novel proteomic and metabolomic signatures were identified. Multi‐organ molecular changes in lipid metabolism, mitochondrial function, and bioenergetics are predicted to impact adipose tissue and liver function and cardiovascular health. Our identification of rapid changes in protein and metabolite signatures with accelerated restoration of metabolic health can be leveraged to evaluate biomarkers of metabolic health and disease in a translational context. |
| format | Article |
| id | doaj-art-c0f90ff32486417c8ea100e2f15ec771 |
| institution | Kabale University |
| issn | 2051-817X |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Wiley |
| record_format | Article |
| series | Physiological Reports |
| spelling | doaj-art-c0f90ff32486417c8ea100e2f15ec7712025-08-20T03:26:48ZengWileyPhysiological Reports2051-817X2025-06-011312n/an/a10.14814/phy2.70405Short‐term dietary methionine restriction with high fat diet counteracts metabolic dysfunction in male miceMarissa I. McGilvrey0Bethany Fortier1Diana Cooke2Maryam A. Mahdi3Benjamin Tero4Christian M. Potts5Abigail Kaija6Larisa Ryzhova7Carolina Cora8Adam Richardson9Douglas Guzior10Ilka Pinz11Calvin Vary12Robert A. Koza13Gene Ables14Lucy Liaw15Center for Molecular Medicine, MaineHealth Institute for Research Scarborough Maine USACenter for Molecular Medicine, MaineHealth Institute for Research Scarborough Maine USAOrentreich Foundation for the Advancement of Science, Inc. Cold Spring New York USACenter for Molecular Medicine, MaineHealth Institute for Research Scarborough Maine USACenter for Molecular Medicine, MaineHealth Institute for Research Scarborough Maine USACenter for Molecular Medicine, MaineHealth Institute for Research Scarborough Maine USACenter for Molecular Medicine, MaineHealth Institute for Research Scarborough Maine USACenter for Molecular Medicine, MaineHealth Institute for Research Scarborough Maine USACenter for Molecular Medicine, MaineHealth Institute for Research Scarborough Maine USAPanome Bio St. Louis Missouri USAPanome Bio St. Louis Missouri USACenter for Molecular Medicine, MaineHealth Institute for Research Scarborough Maine USACenter for Molecular Medicine, MaineHealth Institute for Research Scarborough Maine USACenter for Molecular Medicine, MaineHealth Institute for Research Scarborough Maine USAOrentreich Foundation for the Advancement of Science, Inc. Cold Spring New York USACenter for Molecular Medicine, MaineHealth Institute for Research Scarborough Maine USAAbstract Dietary methionine restriction (MetR) promotes metabolic health, and we tested the impact of short durations of MetR on high fat diet (HFD)‐induced metabolic dysfunction with the maintenance of HFD. Male C57BL/6J mice were fed HFD from 10 to 25 weeks of age, then maintained on HFD or fed HFD with 80% reduced methionine (HFD‐MetR) for 3, 5, or 10 days. Blood, liver, adipose tissue, and aortae underwent phenotypic assessment, proteomics, and metabolomics. HFD‐MetR induced rapid weight loss and robust metabolic improvement within 10 days. Significant reductions in body weight, circulating triglycerides, glucose, insulin, adipokines and hepatokines reflected metabolic health. Proteomics revealed enriched metabolic signatures in perivascular adipose tissue (PVAT) and structural remodeling signatures in aorta. Metabolomics identified a cardioprotective signature in blood plasma, and activated mitochondrial activity and energy production in liver and brown adipose tissue. HFD‐MetR reversed metabolic dysfunction, and novel proteomic and metabolomic signatures were identified. Multi‐organ molecular changes in lipid metabolism, mitochondrial function, and bioenergetics are predicted to impact adipose tissue and liver function and cardiovascular health. Our identification of rapid changes in protein and metabolite signatures with accelerated restoration of metabolic health can be leveraged to evaluate biomarkers of metabolic health and disease in a translational context.https://doi.org/10.14814/phy2.70405adipose tissuehigh fat dietmetabolomicsmethionine restrictionproteomics |
| spellingShingle | Marissa I. McGilvrey Bethany Fortier Diana Cooke Maryam A. Mahdi Benjamin Tero Christian M. Potts Abigail Kaija Larisa Ryzhova Carolina Cora Adam Richardson Douglas Guzior Ilka Pinz Calvin Vary Robert A. Koza Gene Ables Lucy Liaw Short‐term dietary methionine restriction with high fat diet counteracts metabolic dysfunction in male mice Physiological Reports adipose tissue high fat diet metabolomics methionine restriction proteomics |
| title | Short‐term dietary methionine restriction with high fat diet counteracts metabolic dysfunction in male mice |
| title_full | Short‐term dietary methionine restriction with high fat diet counteracts metabolic dysfunction in male mice |
| title_fullStr | Short‐term dietary methionine restriction with high fat diet counteracts metabolic dysfunction in male mice |
| title_full_unstemmed | Short‐term dietary methionine restriction with high fat diet counteracts metabolic dysfunction in male mice |
| title_short | Short‐term dietary methionine restriction with high fat diet counteracts metabolic dysfunction in male mice |
| title_sort | short term dietary methionine restriction with high fat diet counteracts metabolic dysfunction in male mice |
| topic | adipose tissue high fat diet metabolomics methionine restriction proteomics |
| url | https://doi.org/10.14814/phy2.70405 |
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