1877-LB: The Effects and Mechanisms of Caloric Restriction on Diabetic Peripheral Neuropathy

Introduction and Objective: Diabetic peripheral neuropathy is one of the most common complications of diabetes, which can lead to adverse outcomes such as amputation, and currently, there is a lack of effective treatment methods. Fortunately, Caloric restriction(CR) is recognized as an effective measure for managing diabetic complications. Therefore, this study aims to investigate whether CR can ameliorate peripheral neuropathy in diabetic mice and further analyze its underlying mechanisms. Methods: We divided diabetic mice (db/db) into three groups for dietary intervention: the Ad libitum(AL), the Calorie Restriction(CR), the Alternate-Day Fasting(ADF).And evaluated the effects of dietary intervention on the metabolism and peripheral neuropathy of db/db mice. Furthermore, we performed transcriptomic sequencing on sciatic nerve tissue to screen for potential targets and investigated the mechanisms through in vitro experiments. Concurrently, we identified metabolites significantly altered by CR for validation, exploring the impact of metabolite intervention on diabetic peripheral neuropathy. Results: Both CR and ADF improved glucose and lipid metabolism in diabetic mice. Both CR and ADF ameliorated peripheral neuropathy in diabetic mice, reduced the expression of ANGPTL4 in the sciatic nerve, with similar efficacy between the two dietary intervention modes.High glucose and high fat induced ferroptosis in Schwann cells and promoted ANGPTL4 expression. Knockdown of ANGPTL4 inhibited ferroptosis in Schwann cells, and ANGPTL4 mediated ferroptosis by regulating ACSL4 expression. Palmitoleic acid improved peripheral neuropathy in diabetic mice and reduced the expression of ANGPTL4 in the sciatic nerve. Conclusion: Both CR and ADF ameliorate peripheral neuropathy in diabetic mice, with similar efficacy observed between the two interventions. Disclosure W. Jinli: None. M. Ren: None. W. Wang: None. L. Yan: None.