High Energy Diets-Induced Metabolic and Prediabetic Painful Polyneuropathy in Rats

Abstract

To establish the role of the metabolic state in the pathogenesis of polyneuropathy, an age- and sex-matched, longitudinal study in rats fed high-fat and high-sucrose diets (HFSD) or high-fat, high-sucrose and high-salt diets (HFSSD) relative to controls was performed. Time courses of body weight, systolic blood pressure, fasting plasma glucose (FPG), insulin, free fatty acids (FFA), homeostasis model assessment-insulin resistance index (HOMA-IR), thermal and mechanical sensitivity and motor coordination were measured in parallel. Finally, large and small myelinated fibers (LMF, SMF) as well as unmyelinated fibers (UMF) in the sciatic nerves and ascending fibers in the spinal dorsal column were quantitatively assessed under electron microscopy. The results showed that early metabolic syndrome (hyperinsulinemia, dyslipidemia, and hypertension) and prediabetic conditions (impaired fasting glucose) could be induced by high energy diet, and these animals later developed painful polyneuropathy characterized by myelin breakdown and LMF loss in both peripheral and central nervous system. In contrast SMF and UMF in the sciatic nerves were changed little, in the same animals. Therefore the phenomenon that high energy diets induce bilateral mechanical, but not thermal, pain hypersensitivity is reflected by severe damage to LMF, but mild damage to SMF and UMF. Moreover, dietary sodium (high-salt) deteriorates the neuropathic pathological process induced by high energy diets, but paradoxically high salt consumption, may reduce, at least temporarily, chronic pain perception in these animals.

Behavioural, morphological and electrophysiological assessment of the effects of type 2 diabetes mellitus on large and small nerve fibres in Zucker diabetic fatty, Zucker lean and Wistar rats

“…However, all strains used in our study showed a decreased IENF density at age 35 weeks compared to baseline values. Although there are indications in literature that IENF density could be age‐dependent (Chang et al., ; Jelicic Kadic et al., ), we cannot exclude a concomitant influence of the diet used in our study provoking a pre‐type 2 diabetes status, as other studies have reported (Buettner et al., ; Xie et al., ; Song et al., ).…”

Diet-Induced Rodent Models of Diabetic Peripheral Neuropathy, Retinopathy and Nephropathy

“…), sensory nerve density of the skin and cornea as well as thermal and mechanical sensitivity were more significantly impaired, likely reflecting the progressive nature of DPN evolution [44]. It is worth emphasizing the distinct sensitivity to pain between male and female rodents [47], as well as the effect of dietary salt supplementation on DPN hallmarks [45]. Interestingly, male SD albino rats submitted to a high salt/fat/carbohydrate diet (HFSSD: 48% kcal from fat, 37% kcal from CH and 80 g dietary salt/kg diet) for about 16 weeks displayed an aggravated breakdown of large myelin fibers in sciatic nerves when compared with HFSD-fed animals.…”

Effects of normal aging on myelin sheath ultrastructures in the somatic sensorimotor system of rats

“…Measurements of myelin sheath thickness, axon and fiber diameters and g-ratio (which was determined by dividing the axon diameter by the fiber diameter) were obtained using Image-Pro Plus software (Media Cybernetics, Silver Spring, MD, USA). The age-related pathological alterations in the myelin sheath were quantified through pathological grading and counting of the fibers using a method that was established in a previous study by our group (26). Damaged MFs were classified into three grades according to the severity and extent of deterioration, and the percentage of damaged nerve fibers was assessed.…”