Reshaping lipid metabolism with long-term alternate day feeding in type 2 diabetes mice
Abstract Strategies to improve metabolic health include calorie restriction, time restricted eating and fasting several days per week or month. These approaches have demonstrated benefits for individuals experiencing obesity, metabolic syndrome, and prediabetes. However, their impact on established...
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Nature Portfolio
2025-02-01
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| Series: | npj Metabolic Health and Disease |
| Online Access: | https://doi.org/10.1038/s44324-024-00039-w |
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| author | Eleni Beli Yuanqing Yan Leni Moldovan Todd A. Lydic Preethi Krishman Sarah A. Tersey Yaqian Duan Tatiana E. Salazar James M. Dominguez Dung V. Nguyen Abigail Cox Sergio Li Calzi Craig Beam Raghavendra G. Mirmira Carmella Evans-Molina Julia V. Busik Maria B. Grant |
| author_facet | Eleni Beli Yuanqing Yan Leni Moldovan Todd A. Lydic Preethi Krishman Sarah A. Tersey Yaqian Duan Tatiana E. Salazar James M. Dominguez Dung V. Nguyen Abigail Cox Sergio Li Calzi Craig Beam Raghavendra G. Mirmira Carmella Evans-Molina Julia V. Busik Maria B. Grant |
| author_sort | Eleni Beli |
| collection | DOAJ |
| description | Abstract Strategies to improve metabolic health include calorie restriction, time restricted eating and fasting several days per week or month. These approaches have demonstrated benefits for individuals experiencing obesity, metabolic syndrome, and prediabetes. However, their impact on established diabetes remains incompletely studied. The chronicity of type 2 diabetes (T2D) requires that interventions must be undertaken for extended periods of time, typically the entire lifetime of the individual. In this study, we examined the impact of intermittent fasting (IF), with an every-other-day protocol for a duration of 6 months in a murine model of T2D, the db/db (D) mouse on metabolism and liver steatosis. We compared D-IF mice with diabetic ad-libitum (AL; D-AL), control-IF (C-IF) and control-AL (C-AL) cohorts. We demonstrated using lipidomic, microbiome, metabolomic and liver transcriptomic studies that chronic IF improved carbohydrate utilization and glucose homeostasis without weight loss and reduced white adipose tissue inflammation and significantly impacted lipid metabolism in the liver. Microbiome studies and predicted functional analysis of gut microbiota showed that IF increased beneficial bacteria involved in sphingolipid (SL) metabolism. The metabolomic studies showed that oxidation of lipid species and ceramide levels were reduced in D-IF compared to D-AL. The liver lipidomic analysis and liver microarray confirmed a reduction in overall lipid content in D-IF mice compared to D-AL mice, especially in the feeding state as well as an overall reduction in oxidized lipids and ceramides. These studies support that long-term IF can improve glucose homeostasis and dramatically altered lipid metabolism in the absence of weight loss. |
| format | Article |
| id | doaj-art-9e9102970ef64165b2b45702069034cd |
| institution | Kabale University |
| issn | 2948-2828 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Metabolic Health and Disease |
| spelling | doaj-art-9e9102970ef64165b2b45702069034cd2025-02-09T12:11:55ZengNature Portfolionpj Metabolic Health and Disease2948-28282025-02-013111410.1038/s44324-024-00039-wReshaping lipid metabolism with long-term alternate day feeding in type 2 diabetes miceEleni Beli0Yuanqing Yan1Leni Moldovan2Todd A. Lydic3Preethi Krishman4Sarah A. Tersey5Yaqian Duan6Tatiana E. Salazar7James M. Dominguez8Dung V. Nguyen9Abigail Cox10Sergio Li Calzi11Craig Beam12Raghavendra G. Mirmira13Carmella Evans-Molina14Julia V. Busik15Maria B. Grant16Department of Ophthalmology, Indiana University School of MedicineDepartment of Surgery, The Feinberg School of Medicine, Northwestern UniversityDepartment of Ophthalmology, Indiana University School of MedicineDepartment of Physiology, Michigan State UniversityCenter for Diabetes and Metabolic Diseases, and the Herman B Wells Center for Pediatric Research, Indiana University School of MedicineCenter for Diabetes and Metabolic Diseases, and the Herman B Wells Center for Pediatric Research, Indiana University School of MedicineDepartment of Ophthalmology, Indiana University School of MedicineDepartment of Ophthalmology, Indiana University School of MedicineDepartment of Ophthalmology, Indiana University School of MedicineDepartment of Ophthalmology, Indiana University School of MedicineDepartment of Comparative Pathobiology, College of Veterinary Medicine, Purdue UniversityDepartment of Ophthalmology, Indiana University School of MedicineDepartment of Biomedical Sciences, Homer Stryker MD School of Medicine, Western Michigan UniversityCenter for Diabetes and Metabolic Diseases, and the Herman B Wells Center for Pediatric Research, Indiana University School of MedicineCenter for Diabetes and Metabolic Diseases, and the Herman B Wells Center for Pediatric Research, Indiana University School of MedicineDepartment of Physiology, Michigan State UniversityDepartment of Ophthalmology, Indiana University School of MedicineAbstract Strategies to improve metabolic health include calorie restriction, time restricted eating and fasting several days per week or month. These approaches have demonstrated benefits for individuals experiencing obesity, metabolic syndrome, and prediabetes. However, their impact on established diabetes remains incompletely studied. The chronicity of type 2 diabetes (T2D) requires that interventions must be undertaken for extended periods of time, typically the entire lifetime of the individual. In this study, we examined the impact of intermittent fasting (IF), with an every-other-day protocol for a duration of 6 months in a murine model of T2D, the db/db (D) mouse on metabolism and liver steatosis. We compared D-IF mice with diabetic ad-libitum (AL; D-AL), control-IF (C-IF) and control-AL (C-AL) cohorts. We demonstrated using lipidomic, microbiome, metabolomic and liver transcriptomic studies that chronic IF improved carbohydrate utilization and glucose homeostasis without weight loss and reduced white adipose tissue inflammation and significantly impacted lipid metabolism in the liver. Microbiome studies and predicted functional analysis of gut microbiota showed that IF increased beneficial bacteria involved in sphingolipid (SL) metabolism. The metabolomic studies showed that oxidation of lipid species and ceramide levels were reduced in D-IF compared to D-AL. The liver lipidomic analysis and liver microarray confirmed a reduction in overall lipid content in D-IF mice compared to D-AL mice, especially in the feeding state as well as an overall reduction in oxidized lipids and ceramides. These studies support that long-term IF can improve glucose homeostasis and dramatically altered lipid metabolism in the absence of weight loss.https://doi.org/10.1038/s44324-024-00039-w |
| spellingShingle | Eleni Beli Yuanqing Yan Leni Moldovan Todd A. Lydic Preethi Krishman Sarah A. Tersey Yaqian Duan Tatiana E. Salazar James M. Dominguez Dung V. Nguyen Abigail Cox Sergio Li Calzi Craig Beam Raghavendra G. Mirmira Carmella Evans-Molina Julia V. Busik Maria B. Grant Reshaping lipid metabolism with long-term alternate day feeding in type 2 diabetes mice npj Metabolic Health and Disease |
| title | Reshaping lipid metabolism with long-term alternate day feeding in type 2 diabetes mice |
| title_full | Reshaping lipid metabolism with long-term alternate day feeding in type 2 diabetes mice |
| title_fullStr | Reshaping lipid metabolism with long-term alternate day feeding in type 2 diabetes mice |
| title_full_unstemmed | Reshaping lipid metabolism with long-term alternate day feeding in type 2 diabetes mice |
| title_short | Reshaping lipid metabolism with long-term alternate day feeding in type 2 diabetes mice |
| title_sort | reshaping lipid metabolism with long term alternate day feeding in type 2 diabetes mice |
| url | https://doi.org/10.1038/s44324-024-00039-w |
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