The role of dietary non-heme iron load and peripheral nerve inflammation in the development of peripheral neuropathy (PN) in obese non-diabetic leptin-deficient ob/ob mice

Neurol Res. 2019 Apr;41(4):341-353. doi: 10.1080/01616412.2018.1564191. Epub 2019 Jan 13.


Introduction: Here, we investigated inflammatory signs of peripheral nerves in leptin-deficient obese ob/ob mice and the modulating effects of the exogenous iron load.

Methods: Ob/ob and ob/+ control mice were fed with high, standard, or low iron diet for four months.

Results: We found intraepidermal nerve fiber degeneration in foot skin and low-grade neuropathic abnormalities including mildly slowed motor and compound sensory nerve conduction velocities and low-grade macrophage and T-cell infiltration without overt neuropathology in sciatic nerves of all ob/ob mice. Low dietary iron load caused more pronounced abnormalities than high iron load in ob/ob mice.

Discussion: Our data suggest that dietary non-heme iron deficiency may be a modulating factor in the pathogenesis of peripheral neuropathy in obese ob/ob mice with metabolic syndrome. Once the mechanisms can be further elucidated, how low dietary iron augments peripheral nerve degeneration and dysfunction via pro-inflammatory pathways and new therapeutic strategies could be developed.

Abbreviations: CMAP: compound muscle action potential; cSNCV: compound sensory nerve conduction velocity; IENFD: intraepidermal nerve fiber density; LDL: low-density lipoprotein; MetS: metabolic syndrome; MNCV: motor conduction velocity; NCV: nerve conduction velocity; PN: peripheral neuropathy; PNS: peripheral nervous system; STZ: streptozotocin; T2D: type 2 diabetes mellitus; TNF alpha: tumor necrosis factor alpha; WHO: World Health Organization.

Keywords: mice; Peripheral neuropathy; iron; metabolic syndrome; nerve inflammation.

MeSH terms

  • Animals
  • Calcium-Binding Proteins / metabolism
  • Cytokines / metabolism
  • Diabetic Neuropathies / complications*
  • Diabetic Neuropathies / diet therapy*
  • Disease Models, Animal
  • Iron, Dietary / therapeutic use*
  • Leptin / deficiency*
  • Leptin / genetics
  • Male
  • Mice
  • Mice, Mutant Strains
  • Microfilament Proteins / metabolism
  • Microscopy, Electron, Transmission
  • Nerve Fibers / drug effects
  • Nerve Fibers / physiology
  • Nerve Tissue Proteins / metabolism
  • Neural Conduction / genetics
  • Neurogenic Inflammation / etiology*
  • Sciatic Nerve / pathology
  • Sciatic Nerve / ultrastructure
  • Skin / innervation
  • Skin / pathology


  • Aif1 protein, mouse
  • Calcium-Binding Proteins
  • Cytokines
  • Iron, Dietary
  • Leptin
  • Microfilament Proteins
  • Nerve Tissue Proteins