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LMNA-linked lipodystrophies: from altered fat distribution to cellular alterations
- Source :
- Biochemical Society Transactions. 39:1752-1757
- Publication Year :
- 2011
- Publisher :
- Portland Press Ltd., 2011.
-
Abstract
- Mutations in the LMNA gene, encoding the nuclear intermediate filaments the A-type lamins, result in a wide variety of diseases known as laminopathies. Some of them, such as familial partial lipodystrophy of Dunnigan and metabolic laminopathies, are characterized by lipodystrophic syndromes with altered fat distribution and severe metabolic alterations with insulin resistance and dyslipidaemia. Metabolic disturbances could be due either to the inability of adipose tissue to adequately store triacylglycerols or to other cellular alterations linked to A-type lamin mutations. Indeed, abnormal prelamin A accumulation and farnesylation, which are clearly involved in laminopathic premature aging syndromes, could play important roles in lipodystrophies. In addition, gene expression alterations, and signalling abnormalities affecting SREBP1 (sterol-regulatory-element-binding protein 1) and MAPK (mitogen-activated protein kinase) pathways, could participate in the pathophysiological mechanisms leading to LMNA (lamin A/C)-linked metabolic alterations and lipodystrophies. In the present review, we describe the clinical phenotype of LMNA-linked lipodystrophies and discuss the current physiological and biochemical hypotheses regarding the pathophysiology of these diseases.
- Subjects :
- Genetics
Premature aging
Lipodystrophy
integumentary system
Nuclear Proteins
Adipose tissue
Biology
Lamin Type A
Familial partial lipodystrophy
medicine.disease
Biochemistry
Cell biology
LMNA
Insulin resistance
medicine
Humans
Insulin Resistance
Protein Precursors
Signal transduction
Intermediate filament
Lamin
Adiposity
Signal Transduction
Subjects
Details
- ISSN :
- 14708752 and 03005127
- Volume :
- 39
- Database :
- OpenAIRE
- Journal :
- Biochemical Society Transactions
- Accession number :
- edsair.doi.dedup.....b371df7c18d806f55c1154ef99353b78