Sodium benzoate induces pancreatic inflammation and β cell apoptosis partially via benzoylation
Epigenetics, specifically histone post-translational modification (HPTM) induced by environmental factors, plays a crucial role in the development of diabetes. Sodium benzoate (NAB) is a widely used additive, however, its potential contribution to diabetes has been largely overlooked. In 2018, a nov...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-01-01
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| Series: | Ecotoxicology and Environmental Safety |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651323013817 |
| _version_ | 1827377941095383040 |
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| author | Dongze Li Li Zhang Ping Yang Yanqiu He Tingting Zhou Xi Cheng Zongzhe Jiang Yang Long Qin Wan Pijun Yan Chenlin Gao Wei Huang Yong Xu |
| author_facet | Dongze Li Li Zhang Ping Yang Yanqiu He Tingting Zhou Xi Cheng Zongzhe Jiang Yang Long Qin Wan Pijun Yan Chenlin Gao Wei Huang Yong Xu |
| author_sort | Dongze Li |
| collection | DOAJ |
| description | Epigenetics, specifically histone post-translational modification (HPTM) induced by environmental factors, plays a crucial role in the development of diabetes. Sodium benzoate (NAB) is a widely used additive, however, its potential contribution to diabetes has been largely overlooked. In 2018, a novel HPTM called benzoylation (Kbz) induced by NAB was discovered. This modification can be catalyzed by ACSS2 (acyl-CoA synthetase short-chain member 2) and acyltransferase P300/CBP, and can be reversed by erase enzymes SIRT2. Studies have indicated that Kbz may regulate insulin secretion, although the exact molecular mechanism remains unclear. In our study, C57BL/6J mice were divided into two groups: the NC group and the 1g/kg NAB water feeding group. In vivo experiments were conducted using β-TC-6 cells, with 6 mM NAB or 100 μM benzoyl-CoA as stimuli, and 10 μM A485 (P300 inhibitor), 5 μM ACSS2 inhibitor (inhibiting benzoyl-CoA synthesis), or 5 μM AGK2 (SIRT2 inhibitor) as intervention factors. Our study found that, although the experimental concentration of NAB is below the maximum allowable concentration in food, it still damaged the insulin secretion function of C57BL/6J mice and induced inflammation and apoptosis of islet β cells. We observed significant differences in serum benzoyl-CoA levels between healthy individuals and patients with type 2 diabetes. Furthermore, NAB concentration-dependently increases benzoyl-CoA and Kbz levels. When Kbz is down-regulated using A485 and ACSS2 inhibitor, we observed a reduction in β cell inflammation, apoptosis, and insulin secretion damage. Conversely, up-regulating Kbz using AGK2 resulted in increased levels of β cell inflammation and apoptosis. In conclusion, our data suggest that NAB, despite being within the safe dose range, may be an overlooked environmental risk factor contributing to the pathogenesis of diabetes through its impact on Kbz. |
| first_indexed | 2024-03-08T12:47:41Z |
| format | Article |
| id | doaj.art-c02b044b5a68498fac503991e987213d |
| institution | Directory Open Access Journal |
| issn | 0147-6513 |
| language | English |
| last_indexed | 2024-03-08T12:47:41Z |
| publishDate | 2024-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj.art-c02b044b5a68498fac503991e987213d2024-01-21T05:05:16ZengElsevierEcotoxicology and Environmental Safety0147-65132024-01-01270115877Sodium benzoate induces pancreatic inflammation and β cell apoptosis partially via benzoylationDongze Li0Li Zhang1Ping Yang2Yanqiu He3Tingting Zhou4Xi Cheng5Zongzhe Jiang6Yang Long7Qin Wan8Pijun Yan9Chenlin Gao10Wei Huang11Yong Xu12Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China; Sichuan Clinical Research Center for Diabetes and Metabolic Diseases, Luzhou, Sichuan 646000, China; Metabolic Vascular Disease Key Laboratory of Sichuan Province, Luzhou, Sichuan 646000, China; Sichuan Clinical Research Center for Nephropathy, Luzhou, Sichuan 646000, ChinaSichuan Clinical Research Center for Diabetes and Metabolic Diseases, Luzhou, Sichuan 646000, China; Metabolic Vascular Disease Key Laboratory of Sichuan Province, Luzhou, Sichuan 646000, China; Department of Vascular Surgery, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, ChinaDepartment of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China; Sichuan Clinical Research Center for Diabetes and Metabolic Diseases, Luzhou, Sichuan 646000, China; Sichuan Clinical Research Center for Nephropathy, Luzhou, Sichuan 646000, ChinaDepartment of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China; Sichuan Clinical Research Center for Diabetes and Metabolic Diseases, Luzhou, Sichuan 646000, China; Metabolic Vascular Disease Key Laboratory of Sichuan Province, Luzhou, Sichuan 646000, China; Sichuan Clinical Research Center for Nephropathy, Luzhou, Sichuan 646000, ChinaDepartment of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China; Sichuan Clinical Research Center for Diabetes and Metabolic Diseases, Luzhou, Sichuan 646000, China; Metabolic Vascular Disease Key Laboratory of Sichuan Province, Luzhou, Sichuan 646000, China; Sichuan Clinical Research Center for Nephropathy, Luzhou, Sichuan 646000, ChinaDepartment of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China; Sichuan Clinical Research Center for Diabetes and Metabolic Diseases, Luzhou, Sichuan 646000, China; Metabolic Vascular Disease Key Laboratory of Sichuan Province, Luzhou, Sichuan 646000, China; Sichuan Clinical Research Center for Nephropathy, Luzhou, Sichuan 646000, ChinaDepartment of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China; Sichuan Clinical Research Center for Diabetes and Metabolic Diseases, Luzhou, Sichuan 646000, China; Metabolic Vascular Disease Key Laboratory of Sichuan Province, Luzhou, Sichuan 646000, China; Sichuan Clinical Research Center for Nephropathy, Luzhou, Sichuan 646000, ChinaDepartment of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China; Sichuan Clinical Research Center for Diabetes and Metabolic Diseases, Luzhou, Sichuan 646000, China; Metabolic Vascular Disease Key Laboratory of Sichuan Province, Luzhou, Sichuan 646000, China; Sichuan Clinical Research Center for Nephropathy, Luzhou, Sichuan 646000, ChinaDepartment of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China; Sichuan Clinical Research Center for Diabetes and Metabolic Diseases, Luzhou, Sichuan 646000, China; Metabolic Vascular Disease Key Laboratory of Sichuan Province, Luzhou, Sichuan 646000, China; Sichuan Clinical Research Center for Nephropathy, Luzhou, Sichuan 646000, ChinaDepartment of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China; Sichuan Clinical Research Center for Diabetes and Metabolic Diseases, Luzhou, Sichuan 646000, China; Metabolic Vascular Disease Key Laboratory of Sichuan Province, Luzhou, Sichuan 646000, China; Sichuan Clinical Research Center for Nephropathy, Luzhou, Sichuan 646000, ChinaSichuan Clinical Research Center for Diabetes and Metabolic Diseases, Luzhou, Sichuan 646000, China; Metabolic Vascular Disease Key Laboratory of Sichuan Province, Luzhou, Sichuan 646000, China; Sichuan Clinical Research Center for Nephropathy, Luzhou, Sichuan 646000, ChinaDepartment of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China; Sichuan Clinical Research Center for Diabetes and Metabolic Diseases, Luzhou, Sichuan 646000, China; Metabolic Vascular Disease Key Laboratory of Sichuan Province, Luzhou, Sichuan 646000, China; Sichuan Clinical Research Center for Nephropathy, Luzhou, Sichuan 646000, China; Corresponding authors at: Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, ChinaDepartment of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China; Sichuan Clinical Research Center for Diabetes and Metabolic Diseases, Luzhou, Sichuan 646000, China; Metabolic Vascular Disease Key Laboratory of Sichuan Province, Luzhou, Sichuan 646000, China; Sichuan Clinical Research Center for Nephropathy, Luzhou, Sichuan 646000, China; Corresponding authors at: Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, ChinaEpigenetics, specifically histone post-translational modification (HPTM) induced by environmental factors, plays a crucial role in the development of diabetes. Sodium benzoate (NAB) is a widely used additive, however, its potential contribution to diabetes has been largely overlooked. In 2018, a novel HPTM called benzoylation (Kbz) induced by NAB was discovered. This modification can be catalyzed by ACSS2 (acyl-CoA synthetase short-chain member 2) and acyltransferase P300/CBP, and can be reversed by erase enzymes SIRT2. Studies have indicated that Kbz may regulate insulin secretion, although the exact molecular mechanism remains unclear. In our study, C57BL/6J mice were divided into two groups: the NC group and the 1g/kg NAB water feeding group. In vivo experiments were conducted using β-TC-6 cells, with 6 mM NAB or 100 μM benzoyl-CoA as stimuli, and 10 μM A485 (P300 inhibitor), 5 μM ACSS2 inhibitor (inhibiting benzoyl-CoA synthesis), or 5 μM AGK2 (SIRT2 inhibitor) as intervention factors. Our study found that, although the experimental concentration of NAB is below the maximum allowable concentration in food, it still damaged the insulin secretion function of C57BL/6J mice and induced inflammation and apoptosis of islet β cells. We observed significant differences in serum benzoyl-CoA levels between healthy individuals and patients with type 2 diabetes. Furthermore, NAB concentration-dependently increases benzoyl-CoA and Kbz levels. When Kbz is down-regulated using A485 and ACSS2 inhibitor, we observed a reduction in β cell inflammation, apoptosis, and insulin secretion damage. Conversely, up-regulating Kbz using AGK2 resulted in increased levels of β cell inflammation and apoptosis. In conclusion, our data suggest that NAB, despite being within the safe dose range, may be an overlooked environmental risk factor contributing to the pathogenesis of diabetes through its impact on Kbz.http://www.sciencedirect.com/science/article/pii/S0147651323013817Sodium benzoateBenzoylationInflammationApoptosisDiabetes |
| spellingShingle | Dongze Li Li Zhang Ping Yang Yanqiu He Tingting Zhou Xi Cheng Zongzhe Jiang Yang Long Qin Wan Pijun Yan Chenlin Gao Wei Huang Yong Xu Sodium benzoate induces pancreatic inflammation and β cell apoptosis partially via benzoylation Ecotoxicology and Environmental Safety Sodium benzoate Benzoylation Inflammation Apoptosis Diabetes |
| title | Sodium benzoate induces pancreatic inflammation and β cell apoptosis partially via benzoylation |
| title_full | Sodium benzoate induces pancreatic inflammation and β cell apoptosis partially via benzoylation |
| title_fullStr | Sodium benzoate induces pancreatic inflammation and β cell apoptosis partially via benzoylation |
| title_full_unstemmed | Sodium benzoate induces pancreatic inflammation and β cell apoptosis partially via benzoylation |
| title_short | Sodium benzoate induces pancreatic inflammation and β cell apoptosis partially via benzoylation |
| title_sort | sodium benzoate induces pancreatic inflammation and β cell apoptosis partially via benzoylation |
| topic | Sodium benzoate Benzoylation Inflammation Apoptosis Diabetes |
| url | http://www.sciencedirect.com/science/article/pii/S0147651323013817 |
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