Diabetic peripheral neuropathy represents a considerable medical problem in humans especially because the molecular mechanism of this disease is still obscure. This pathology induces neurological complications on both nerve function and structure. Myelin is a biological membrane characterized by high lipid content and it is one of the main structures that contribute to a correct function of the nervous system. The particular characteristics of the lipids present in the myelin sheath provide the electrically insulating property required for the salutatory propagation of the nervous influx. Liver X Receptors (LXRs) belong to nuclear receptors family and they are ligand-activated transcription factors. The physiological role of LXRs is to avoid harmful concentrations of cholesterol within the cells by activating a battery of genes involved in cholesterol efflux. Besides regulating homeostasis, LXRs directly activate the expression of the lipogenic transcription factor Sterol Regulatory Element Binding Protein-1c (SREBP-1c), a gene involved in fatty acid synthesis. Recently, it has been highlighted the role of SREBP-1c in the regulation of lipid metabolism during peripheral nerve myelination. Using streptozotocin (STZ)-treated rats, an experimental model of diabetic neuropathy, we observed that LXRs activation by GW3965 (a synthetic ligand) counteracts alterations in myelin caused by diabetes by improving myelin lipid content and restoring the expression levels of all major enzymes involved in fatty acid synthesis. We also found that diabetes decreased thermal sensitivity and nerve conduction velocity in STZ-treated rats, parameters restored at the level of non-diabetic animals by the treatment with the LXR ligand GW3965. These results suggest that increased lipogenesis in sciatic nerve of diabetic rats may protect peripheral nerves from neuropathy.
Liver X receptor activation protects from diabetic neuropathy by restoring fatty acid biosynthesis / N. Mitro, G. Cermenati, F. Abbiati, E. Brioschi, S. Giatti, S. Cermenati, R. Bianchi, A. Volonterio, G. Cavaletti, L.M. Garcia Segura, R.C. Melcangi, E. De Fabiani, M. Crestani, D. Caruso. - In: THE FEBS JOURNAL. - ISSN 1742-464X. - 278:Suppl. 1(2011 Jun), pp. 269-269. ((Intervento presentato al 36. convegno FEBS Congress tenutosi a Torino nel 2011 [10.1111/j.1742-4658.2011.08259.x].
|Titolo:||Liver X receptor activation protects from diabetic neuropathy by restoring fatty acid biosynthesis|
MITRO, NICO (Primo)
CERMENATI, GAIA (Secondo)
CRESTANI, MAURIZIO (Penultimo)
CARUSO, DONATELLA MARIA (Ultimo)
|Settore Scientifico Disciplinare:||Settore BIO/10 - Biochimica|
Settore MED/13 - Endocrinologia
|Data di pubblicazione:||giu-2011|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1111/j.1742-4658.2011.08259.x|
|Appare nelle tipologie:||01 - Articolo su periodico|