- Lecture presentation
- Open Access
The lipogenic regulator Sterol Regulatory Element Binding Factor-1c is required to maintain peripheral nerve structure and function
© Mitro et al. 2015
- Published: 12 June 2015
- Peripheral neuropathy
- Schwann cells
Myelin is a membrane characterized by high lipid content to facilitate impulse propagation. Changes in myelin fatty acid (FA) composition have been associated with peripheral neuropathy , but the specific role of peripheral nerve FA synthesis in myelin formation and function is poorly understood. We explored the extent to which lack of the key regulator of FA synthesis as Sterol Regulatory Element Binding Factor-1c (Srebf-1c) could result in the development of peripheral neuropathy. We found that Srebf-1c null mice display a neuropathic phenotype consisting in hypermyelinated small caliber fibers, the result of changes in myelin periodicity. Unexpectedly, transcriptomics and metabolomics revealed activation of peroxisome proliferator activated receptor α (Pparα) signaling in Srebf-1c null peripheral nerve as a result of increased levels of two distinct phosphatidylcholine-based Pparα ligands, PC-C16:0/C18:1 and PC-C18:0/C18:1 [2, 3]. Pparα is a nuclear receptor that directs uptake, utilization and catabolism of FAs . As a consequence of abnormal local Pparα activation, Srebf-1c null peripheral nerve exhibit increased fatty acid utilization, a detrimental condition leading to peripheral neuropathy. Treatment with a Pparα antagonist rescues the neuropathy of Srebf-1c null mice. These findings reveal the importance of FA synthesis to sustain peripheral nerve structure and function.
This study was supported by the Giovanni Armenise-Harvard Foundation (N.M.), Fondazione CARIPLO 2014-0991 (N.M.) and 2012-0547 (R.C.M.), Italian Ministry of Health GR-2011-02346791 (M.D. and N.M.) and Research Center for the Characterization and Safe Use of Natural Compounds – “Giovanni Galli” directed by D.C.
- Cermenati G, et al.: . J Lipid Res 2012, 53: 300-310. 10.1194/jlr.M021188View ArticleGoogle Scholar
- Chakravarthy M.V., et al.: . Cell 2009, 138: 476-488. 10.1016/j.cell.2009.05.036View ArticleGoogle Scholar
- Liu S, et al.: . Nature 2013, 502: 550-554. 10.1038/nature12710View ArticleGoogle Scholar
- Bantubungi K, et al.: . J Steroid Biochem Mol Biol 2012,130():126-137. 10.1016/j.jsbmb.2011.10.002View ArticleGoogle Scholar
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.