2. Academic Validation
  3. Sodium benzoate induces pancreatic inflammation and β cell apoptosis partially via benzoylation

Sodium benzoate induces pancreatic inflammation and β cell apoptosis partially via benzoylation

  • Ecotoxicol Environ Saf. 2023 Dec 26:270:115877. doi: 10.1016/j.ecoenv.2023.115877.
Dongze Li 1,  Li Zhang 2,  Ping Yang 3,  Yanqiu He 1,  Tingting Zhou 1,  Xi Cheng 1,  Zongzhe Jiang 1,  Yang Long 1,  Qin Wan 1,  Pijun Yan 1,  Chenlin Gao 4,  Wei Huang 5,  Yong Xu 6
Affiliations

Affiliations

  • 1 Department 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.
  • 2 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; Department of Vascular Surgery, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China.
  • 3 Department 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, China.
  • 4 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.
  • 5 Department 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. Electronic address: [email protected].
  • 6 Department 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. Electronic address: [email protected].
PMID: 38150747 DOI: 10.1016/j.ecoenv.2023.115877
Abstract

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.

Keywords

Apoptosis; Benzoylation; Diabetes; Inflammation; Sodium benzoate.

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