Influence of intermittent fasting on prediabetes-induced neuropathy: Insights on a novel mechanistic pathway
Aims: Peripheral neuropathy (PN) is correlated with obesity and metabolic syndrome. Intermittent fasting (IF) has been described as the cornerstone in the management of obesity; however, its role in prediabetic complications is not well elucidated. Cytochromes P450 Monooxygenases (CYP450) are major...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-06-01
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| Series: | Metabolism Open |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589936822000135 |
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| author | Maya Dannawi Mansour E. Riachi Antony F. Haddad Mohamed El Massry Mary Haddad Pamela Moukarzel Frédéric Harb Hilda E. Ghadieh Assaad A. Eid |
| author_facet | Maya Dannawi Mansour E. Riachi Antony F. Haddad Mohamed El Massry Mary Haddad Pamela Moukarzel Frédéric Harb Hilda E. Ghadieh Assaad A. Eid |
| author_sort | Maya Dannawi |
| collection | DOAJ |
| description | Aims: Peripheral neuropathy (PN) is correlated with obesity and metabolic syndrome. Intermittent fasting (IF) has been described as the cornerstone in the management of obesity; however, its role in prediabetic complications is not well elucidated. Cytochromes P450 Monooxygenases (CYP450) are major sources of Reactive Oxygen Species (ROS) that orchestrate the onset and development of diabetic complications. One of the CYP-metabolites, Expoxyecosatetraenoic Acids (EETs), are considered to be negative regulators of ROS production. In this study, we elucidated the role of IF on ROS production and investigated its influence on prediabetes-induced PN. Methods: C57/BL6 control mice, prediabetic, prediabetic that underwent alternate day fasting with different diet composition, and prediabetic mice treated with EET-metabolizing sEH-inhibitor, AUDA. Body mass composition, metabolic, behavioral, and molecular tests were performed. Results: High-fat diet (HFD) led to an increase in NADPH-induced ROS production; that was due to an alteration in the epoxygenase pathway assessed by the decrease in CYP1a1/1a2 expression. IF reinstated the homeostatic levels of EETs in HFD-fed mice. Moreover, treatment with AUDA mimicked the beneficial effect observed with IF. Conclusion: IF and EETs bioavailability have a protective role in prediabetes-induced PN, suggesting a novel interventional strategy in the management of prediabetes and its associated complications. |
| first_indexed | 2024-04-12T16:20:44Z |
| format | Article |
| id | doaj.art-3266c5b54bc54665b7a9bbc3390e59b2 |
| institution | Directory Open Access Journal |
| issn | 2589-9368 |
| language | English |
| last_indexed | 2024-04-12T16:20:44Z |
| publishDate | 2022-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Metabolism Open |
| spelling | doaj.art-3266c5b54bc54665b7a9bbc3390e59b22022-12-22T03:25:33ZengElsevierMetabolism Open2589-93682022-06-0114100175Influence of intermittent fasting on prediabetes-induced neuropathy: Insights on a novel mechanistic pathwayMaya Dannawi0Mansour E. Riachi1Antony F. Haddad2Mohamed El Massry3Mary Haddad4Pamela Moukarzel5Frédéric Harb6Hilda E. Ghadieh7Assaad A. Eid8Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine and Medical Center, American University of Beirut, Beirut, Lebanon; AUB Diabetes, American University of Beirut, Faculty of Medicine, Medical Center, LebanonDepartment of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine and Medical Center, American University of Beirut, Beirut, Lebanon; AUB Diabetes, American University of Beirut, Faculty of Medicine, Medical Center, LebanonDepartment of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine and Medical Center, American University of Beirut, Beirut, Lebanon; AUB Diabetes, American University of Beirut, Faculty of Medicine, Medical Center, LebanonDepartment of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine and Medical Center, American University of Beirut, Beirut, Lebanon; AUB Diabetes, American University of Beirut, Faculty of Medicine, Medical Center, LebanonDepartment of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine and Medical Center, American University of Beirut, Beirut, Lebanon; AUB Diabetes, American University of Beirut, Faculty of Medicine, Medical Center, LebanonDepartment of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine and Medical Center, American University of Beirut, Beirut, Lebanon; AUB Diabetes, American University of Beirut, Faculty of Medicine, Medical Center, LebanonDepartment of Life and Earth Sciences, Faculty of Sciences, Lebanese University, Fanar, LebanonDepartment of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine and Medical Center, American University of Beirut, Beirut, Lebanon; AUB Diabetes, American University of Beirut, Faculty of Medicine, Medical Center, LebanonDepartment of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine and Medical Center, American University of Beirut, Beirut, Lebanon; AUB Diabetes, American University of Beirut, Faculty of Medicine, Medical Center, Lebanon; Corresponding author. Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine and Medical Center, American University of Beirut, Bliss Street, 11-0236, Riad El-Solh, 1107-2020, Lebanon.Aims: Peripheral neuropathy (PN) is correlated with obesity and metabolic syndrome. Intermittent fasting (IF) has been described as the cornerstone in the management of obesity; however, its role in prediabetic complications is not well elucidated. Cytochromes P450 Monooxygenases (CYP450) are major sources of Reactive Oxygen Species (ROS) that orchestrate the onset and development of diabetic complications. One of the CYP-metabolites, Expoxyecosatetraenoic Acids (EETs), are considered to be negative regulators of ROS production. In this study, we elucidated the role of IF on ROS production and investigated its influence on prediabetes-induced PN. Methods: C57/BL6 control mice, prediabetic, prediabetic that underwent alternate day fasting with different diet composition, and prediabetic mice treated with EET-metabolizing sEH-inhibitor, AUDA. Body mass composition, metabolic, behavioral, and molecular tests were performed. Results: High-fat diet (HFD) led to an increase in NADPH-induced ROS production; that was due to an alteration in the epoxygenase pathway assessed by the decrease in CYP1a1/1a2 expression. IF reinstated the homeostatic levels of EETs in HFD-fed mice. Moreover, treatment with AUDA mimicked the beneficial effect observed with IF. Conclusion: IF and EETs bioavailability have a protective role in prediabetes-induced PN, suggesting a novel interventional strategy in the management of prediabetes and its associated complications.http://www.sciencedirect.com/science/article/pii/S2589936822000135Intermittent fastingReactive oxygen speciesDiabetic peripheral neuropathyDiabetesOxidative stress |
| spellingShingle | Maya Dannawi Mansour E. Riachi Antony F. Haddad Mohamed El Massry Mary Haddad Pamela Moukarzel Frédéric Harb Hilda E. Ghadieh Assaad A. Eid Influence of intermittent fasting on prediabetes-induced neuropathy: Insights on a novel mechanistic pathway Metabolism Open Intermittent fasting Reactive oxygen species Diabetic peripheral neuropathy Diabetes Oxidative stress |
| title | Influence of intermittent fasting on prediabetes-induced neuropathy: Insights on a novel mechanistic pathway |
| title_full | Influence of intermittent fasting on prediabetes-induced neuropathy: Insights on a novel mechanistic pathway |
| title_fullStr | Influence of intermittent fasting on prediabetes-induced neuropathy: Insights on a novel mechanistic pathway |
| title_full_unstemmed | Influence of intermittent fasting on prediabetes-induced neuropathy: Insights on a novel mechanistic pathway |
| title_short | Influence of intermittent fasting on prediabetes-induced neuropathy: Insights on a novel mechanistic pathway |
| title_sort | influence of intermittent fasting on prediabetes induced neuropathy insights on a novel mechanistic pathway |
| topic | Intermittent fasting Reactive oxygen species Diabetic peripheral neuropathy Diabetes Oxidative stress |
| url | http://www.sciencedirect.com/science/article/pii/S2589936822000135 |
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