High energy diets-induced metabolic and prediabetic painful polyneuropathy in rats

PLoS One. 2013;8(2):e57427. doi: 10.1371/journal.pone.0057427. Epub 2013 Feb 25.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Glucose / metabolism
  • Body Weight / physiology
  • Diet / adverse effects*
  • Diet, High-Fat / adverse effects
  • Dietary Sucrose / administration & dosage
  • Dietary Sucrose / adverse effects
  • Fasting / metabolism
  • Fasting / physiology
  • Fatty Acids, Nonesterified / metabolism
  • Homeostasis / physiology
  • Insulin / metabolism
  • Insulin Resistance / physiology
  • Longitudinal Studies
  • Male
  • Metabolic Syndrome / metabolism
  • Metabolic Syndrome / pathology*
  • Motor Skills / physiology
  • Nerve Fibers, Myelinated / metabolism
  • Nerve Fibers, Myelinated / physiology
  • Nerve Fibers, Unmyelinated / metabolism
  • Nerve Fibers, Unmyelinated / physiology
  • Pain / etiology
  • Pain / metabolism
  • Pain / pathology*
  • Polyneuropathies / metabolism
  • Polyneuropathies / pathology*
  • Prediabetic State / metabolism*
  • Prediabetic State / pathology*
  • Rats
  • Rats, Sprague-Dawley
  • Sciatic Nerve / metabolism
  • Sciatic Nerve / physiology
  • Sodium, Dietary / adverse effects
  • Spinal Cord / metabolism
  • Spinal Cord / physiology

Substances

  • Blood Glucose
  • Dietary Sucrose
  • Fatty Acids, Nonesterified
  • Insulin
  • Sodium, Dietary