Effect of enriching the diet with menhaden oil or daily treatment with resolvin D1 on neuropathy in a mouse model of type 2 diabetes

J Neurophysiol. 2015 Jul;114(1):199-208. doi: 10.1152/jn.00224.2015. Epub 2015 Apr 29.


The purpose of this study was to determine the effect of supplementing the diet of a mouse model of type 2 diabetes with menhaden (fish) oil or daily treatment with resolvin D1 on diabetic neuropathy. The end points evaluated included motor and sensory nerve conduction velocity, thermal sensitivity, innervation of sensory nerves in the cornea and skin, and the retinal ganglion cell complex thickness. Menhaden oil is a natural source for n-3 polyunsaturated fatty acids, which have been shown to have beneficial effects in other diseases. Resolvin D1 is a metabolite of docosahexaenoic acid and is known to have anti-inflammatory and neuroprotective properties. To model type 2 diabetes, mice were fed a high-fat diet for 8 wk followed by a low dosage of streptozotocin. After 8 wk of hyperglycemia, mice in experimental groups were treated for 6 wk with menhaden oil in the diet or daily injections of 1 ng/g body wt resolvin D1. Our findings show that menhaden oil or resolvin D1 did not improve elevated blood glucose, HbA1C, or glucose utilization. Untreated diabetic mice were thermal hypoalgesic, had reduced motor and sensory nerve conduction velocities, had decreased innervation of the cornea and skin, and had thinner retinal ganglion cell complex. These end points were significantly improved with menhaden oil or resolvin D1 treatment. Exogenously, resolvin D1 stimulated neurite outgrowth from primary cultures of dorsal root ganglion neurons from normal mice. These studies suggest that n-3 polyunsaturated fatty acids derived from fish oil could be an effective treatment for diabetic neuropathy.

Keywords: corneal nerve fibers; diabetic neuropathy; epidermal nerve fibers; fish oil; resolvin; type 2 diabetes.

Publication types

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

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Cells, Cultured
  • Cornea / innervation
  • Cornea / pathology
  • Diabetes Mellitus, Experimental / diet therapy
  • Diabetes Mellitus, Experimental / drug therapy
  • Diabetes Mellitus, Experimental / pathology
  • Diabetes Mellitus, Experimental / physiopathology*
  • Diabetes Mellitus, Type 2
  • Diabetic Neuropathies / diet therapy*
  • Diabetic Neuropathies / drug therapy*
  • Diabetic Neuropathies / pathology
  • Diabetic Neuropathies / physiopathology
  • Diet, High-Fat
  • Dietary Supplements
  • Docosahexaenoic Acids / pharmacology*
  • Fish Oils / administration & dosage*
  • Ganglia, Spinal / drug effects
  • Ganglia, Spinal / physiology
  • Hot Temperature
  • Hyperalgesia / diet therapy
  • Hyperalgesia / drug therapy
  • Hyperalgesia / physiopathology
  • Mice, Inbred C57BL
  • Neural Conduction / physiology
  • Neurites / drug effects
  • Neurites / physiology
  • Neurons / drug effects
  • Neurons / pathology
  • Neurons / physiology
  • Neuroprotective Agents / pharmacology
  • Retinal Ganglion Cells / pathology
  • Skin / innervation
  • Skin / pathology


  • Anti-Inflammatory Agents
  • Fish Oils
  • Neuroprotective Agents
  • resolvin D1
  • Menhaden oil
  • Docosahexaenoic Acids