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

• Published in: Molecular neurobiology Vol. 58; no. 11; pp. 6049 - 6061
• Main Authors: Wang, Meijian, Xie, Min, Yu, Shuyan, Shang, Pan, Zhang, Cong, Han, Xiaolin, Fan, Cuiqin, Chen, Li, Zhuang, Xianghua, Chen, Shihong
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.11.2021; Springer Nature B.V
• Subjects: Acid phosphatase; Animals; Apoptosis; Autophagy; Autophagy - physiology; Biomedical and Life Sciences; Biomedicine; Cell Biology; Cells, Cultured; Demyelinating Diseases - etiology; Demyelinating Diseases - physiopathology; Demyelinating Diseases - therapy; Demyelination; Diabetes; Diabetes mellitus; Diabetes Mellitus, Experimental - blood; Diabetes Mellitus, Experimental - complications; Diabetic Neuropathies - physiopathology; Diglycerides; Diglycerides - biosynthesis; Down-Regulation; Gene Knockdown Techniques; Genetic Vectors - therapeutic use; Hyperactivity; Hyperalgesia - etiology; Hyperalgesia - therapy; Hyperglycemia; Hyperglycemia - etiology; Hyperglycemia - metabolism; Male; Nerve conduction; Nerve Degeneration - etiology; Nerve Degeneration - physiopathology; Neural Conduction; Neurobiology; Neurodegenerative diseases; Neurology; Neuroprotection; Neurosciences; Nuclear Proteins - biosynthesis; Nuclear Proteins - genetics; Nuclear Proteins - physiology; Nuclear Proteins - therapeutic use; Pathogenesis; Peripheral nerves; Peripheral neuropathy; Phagocytosis; Phenotypes; Phosphatidic acid; Phospholipids; Rats; Rats, Wistar; Recombinant Proteins - metabolism; Schwann cells; Schwann Cells - metabolism; Sciatic nerve; Sciatic Nerve - physiopathology; Streptozocin; RCS96 cell; Diabetic peripheral neuropathy; Lipin1; Autophagy; Sciatic nerve
• ISSN: 0893-7648; 1559-1182; 1559-1182
• DOI: 10.1007/s12035-021-02540-5

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.