Local regulation of fat metabolism in peripheral nerves
Details
Serval ID
serval:BIB_99B269CE6B2F
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Local regulation of fat metabolism in peripheral nerves
Journal
Genes and Development
ISSN
0890-9369 (Print)
Publication state
Published
Issued date
10/2003
Volume
17
Number
19
Pages
2450-64
Notes
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S. --- Old month value: Oct 1
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S. --- Old month value: Oct 1
Abstract
We comprehensively analyzed gene expression during peripheral nerve development by performing microarray analyses of premyelinating, myelinating, and postmyelinating mouse sciatic nerves, and we generated a database of candidate genes to be tested in mapped peripheral neuropathies. Unexpectedly, we identified a large cluster of genes that are (1) maximally expressed only in the mature nerve, after myelination is complete, and (2) tied to the metabolism of storage (energy) lipids. Many of these late-onset genes are expressed by adipocytes, which we find constitute the bulk of the epineurial compartment of the adult nerve. However, several such genes, including SREBP-1, SREBP-2, and Lpin1, are also expressed in the endoneurium. We find that Lpin1 null mutations lead to lipoatrophy of the epineurium, and to the dysregulation of a battery of genes required for the regulation of storage lipid metabolism in both the endoneurium and peri/epineurium. Together with the observation that these mutations also result in peripheral neuropathy, our findings demonstrate a crucial role for local storage lipid metabolism in mature peripheral nerve function, and have important implications for the understanding and treatment of peripheral neuropathies that are commonly associated with metabolic diseases such as lipodystrophy and diabetes.
Keywords
Adipocytes/physiology
Animals
CCAAT-Enhancer-Binding Proteins/genetics
DNA-Binding Proteins/genetics
*Gene Expression Regulation, Developmental
*Lipid Metabolism
Mice
Mice, Mutant Strains
Multigene Family
Mutation
Myelin Sheath/metabolism
Nuclear Proteins/genetics
Oligonucleotide Array Sequence Analysis
Peripheral Nervous System Diseases/*genetics/pathology
Sciatic Nerve/embryology/*metabolism/physiology
Sterol Regulatory Element Binding Protein 1
Sterol Regulatory Element Binding Protein 2
Transcription Factors/genetics
Pubmed
Web of science
Open Access
Yes
Create date
24/01/2008 15:12
Last modification date
20/08/2019 16:01