The role of oxidative stress and inflammatory response in high-fat diet induced peripheral neuropathy

Earlier studies suggest that high-calorie diet is an important risk factor for neuronal damage resulting from oxidative stress of lipid metabolism. In our experimental study of rats under high-fat diet, oxidative stress markers and axonal degeneration parameters were used to observe the sciatic nerve neuropathy. The aim of this study is to evaluate the pathophysiology of neuropathy induced by high-fat diet.

A total of 14 male rats (Wistar albino) were randomly divided into two experimental groups as follows; control group (n=7) and the model group (n=7); while control group was fed with standard diet; where the model group was fed with a high-fat diet for 12 weeks. At the end of 12 weeks, the lipid profile and blood glucose levels, interleukin-1β (IL-1), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and transforming growth factor-β (TGF-β) levels were studied. Tissue malondialdehyde (MDA), nitric oxide (NO) levels and super-oxide dismutase (SOD), paraoxonase-1 (PON-1) and glutathione peroxidase (GPx) activities were studied. The distal blocks of the left sciatic nerves were evaluated for histomorphological analysis (including mean axon area, axon numbers, nerve fiber diameters, axon diameters, and thickness of myelin sheets).

Body weights, serum glucose and high-density lipoprotein (HDL) levels of rats were found not statistically significantly different compared between the model and the control groups (p>0.05). Serum cholesterol, triglyceride, TGF-β and TNF-α levels were significantly higher in the model group when compared with the control group (p<0.05). IL-1 and IL-6 levels were not statistically significantly different compared between the model group and the control group (p>0.05). The MDA and NO levels and the SOD and GPx activities of the sciatic nerves in model group were statistically significantly higher than the control group (p<0.05). In addition, the activities of PON-1 were statistically significantly lower in the model group when compared with the control group (p<0.05). The difference in the total number of myelinated axons between the control group and the model group was not statistically significant (p>0.05). The nerve fiber diameter and the thickness of the myelin sheet were statistically significantly lower in the model group when compared with the control group (p<0.05). The axon diameter and area were significantly decreased in the model group when compared with the control group (p<0.05).

Our results support that dyslipidemia is an independent risk factor for the development of neuropathy. In addition, we postulated that oxidative stress and inflammatory response may play an important role in the pathogenesis of high-fat diet induced neuropathy.