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Diabetes-induced myelin abnormalities are associated with an altered lipid pattern: Protective effects of lxr activation

Academic Article
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Overview

authors

  • Cermenati, G.
  • Abbiati, F.
  • Cermenati, S.
  • Brioschi, E.
  • Volonterio, A.
  • Cavaletti, G.
  • Saez, Enrique
  • De Fabiani, E.
  • Crestani, M.
  • Garcia-Segura, L. M.
  • Melcangi, R. C.
  • Caruso, D.
  • Mitro, N.

publication date

  • February 2012

journal

  • Journal of Lipid Research  Journal

abstract

  • Diabetic peripheral neuropathy (DPN) is characterized by myelin abnormalities; however, the molecular mechanisms underlying such deficits remain obscure. To uncover the effects of diabetes on myelin alterations, we have analyzed myelin composition. In a streptozotocin-treated rat model of diabetic neuropathy, analysis of sciatic nerve myelin lipids revealed that diabetes alters myelin's phospholipid, FA, and cholesterol content in a pattern that can modify membrane fluidity. Reduced expression of relevant genes in the FA biosynthetic pathway and decreased levels of the transcriptionally active form of the lipogenic factor sterol-regulatory element binding factor-1c (SREBF-1c) were found in diabetic sciatic nerve. Expression of myelin's major protein, myelin protein zero (P0), was also suppressed by diabetes. In addition, we confirmed that diabetes induces sciatic nerve myelin abnormalities, primarily infoldings that have previously been associated with altered membrane fluidity. In a diabetic setting, synthetic activator of the nuclear receptor liver X receptor (LXR) increased SREBF-1c function and restored myelin lipid species and P0 expression levels to normal. These LXR-modulated improvements were associated with restored myelin structure in sciatic nerve and enhanced performance in functional tests such as thermal nociceptive threshold and nerve conduction velocity. These findings demonstrate an important role for the LXR-SREBF-1c axis in protection from diabetes-induced myelin abnormalities.

subject areas

  • Animals
  • Cholesterol
  • Diabetes Mellitus, Experimental
  • Gene Expression Regulation
  • Lipids
  • Male
  • Myelin P0 Protein
  • Myelin Sheath
  • Orphan Nuclear Receptors
  • Phospholipids
  • Protein Kinases
  • Rats
  • Rats, Sprague-Dawley
  • Sciatic Nerve
  • Stearoyl-CoA Desaturase
  • Sterol Regulatory Element Binding Protein 1
  • Streptozocin
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Research

keywords

  • diabetic neuropathy
  • fatty acid synthesis
  • liver X receptor
  • myelin composition
  • peripheral nerve
  • sterol-regulatory element binding factor-1c
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Identity

PubMed Central ID

  • PMC3269154

International Standard Serial Number (ISSN)

  • 0022-2275

Digital Object Identifier (DOI)

  • 10.1194/jlr.M021188

PubMed ID

  • 22158827
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Additional Document Info

start page

  • 300

end page

  • 310

volume

  • 53

issue

  • 2

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