Lipin1 Alleviates Autophagy Disorder in Sciatic Nerve and Improves Diabetic Peripheral Neuropathy.

Shuyan Yu,Pan Shang,Shihong Chen,Min Xie,Xiaolin Han,Meijian Wang,Xianghua Zhuang,Cong Zhang,Cuiqin Fan,Li Chen

doi:10.1007/s12035-021-02540-5

Abstract

Diabetic peripheral neuropathy (DPN) is a chronic complication of diabetes, and its neural mechanisms underlying the pathogenesis remain unclear. Autophagy plays an important role in neurodegenerative diseases and nerve tissue injury. Lipin1 is a phosphatidic acid phosphatase enzyme that converts phosphatidic acid (PA) into diacylglycerol (DAG), a precursor of triacylglycerol and phospholipids which plays an important role in maintaining normal peripheral nerve conduction function. However, whether Lipin1 involved in the pathogenesis of DPN via regulation of autophagy is not elucidated. Here, we show that the Lipin1 expression was downregulated in streptozotocin (STZ)-induced DPN rat model. Interestingly, STZ prevented DAG synthesis, and resulted in autophagic hyperactivity, effects which may increase the apoptosis of Schwann cells and lead to demyelination in sciatic nerve in DPN rats. More importantly, upregulation of lipin1 in the DPN rats ameliorated autophagy disorders and pathological changes of the sciatic nerve, which associated with the increase of the motor nerve conductive velocity (MNCV) in DPN rats. In contrast, knockdown of lipin1 exacerbates neuronal abnormalities and facilitates the genesis of DPN phenotypes in rats. In addition, overexpression of lipin1 in RSC96 cells also significantly decreased the autophagic hyperactivity and apoptosis induced by hyperglycemia. These results suggest that lipin1 may exert neuroprotection within the sciatic nerve anomalies and may serve as a potential therapeutic target for the treatment of DPN.

Highlights

With the development of economy and the progress of society, the incidence of diabetes is increasing worldwide [1, 2]
Lipin1 expression is decreased in Diabetic peripheral neuropathy (DPN) rats
We intraperitoneally injected STZ (55 mg/kg) to induce DPN in the rat model, and we found that from the third day after STZ injection, body weights were significantly decreased (P

Summary

Introduction

With the development of economy and the progress of society, the incidence of diabetes is increasing worldwide [1, 2]. The incidence of chronic complications of diabetes increases with prolonged human life and improved medical conditions [3, 4]. Diabetic peripheral neuropathy (DPN) is a chronic complication of diabetes that is knotty and ineffective [5]. Patients may have spontaneous pain, hyperalgesia, acupuncture-like pain, and other symptoms, which may lead to diabetic foot ulcer, gangrene, or amputation. This condition severely affects the quality of life of patients [6, 7]. No specific etiology treatment has been established and must be solved in the medical field

Methods

Results

Discussion

Conclusion