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Human Molecular Genetics Advance Access published online on January 13, 2006
Human Molecular Genetics, doi:10.1093/hmg/ddi480
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© The Author 2006. Published by Oxford University Press. All rights reserved
Received December 1, 2005
Revised January 6, 2006
Accepted January 6, 2006

Article

Nuclear lamin A inhibits adipocyte differentiation: Implications for Dunnigan-type familial partial lipodystrophy

Revekka L. Boguslavsky 1, Colin L. Stewart 2, and Howard J. Worman 3 *

1 Departments Medicine and of Anatomy and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, NY 10032
2 Cancer and Developmental Biology Laboratory, National Cancer Institute, Frederick, MD 21702
3 Department of Medicine and of Anatomy and Cell Biology, College of Physicians and Surgeons Columbia University, 630 West 168th St., 10th Floor, Room 509, New York, NY 10032

* To whom correspondence should be addressed.
Howard J. Worman, E-mail: hjw14{at}columbia.edu


  Abstract

Mutations in the LMNA gene encoding A-type lamins cause several diseases, including Emery-Dreifuss muscular dystrophy and Dunnigan-type familial partial lipodystrophy. We analyzed differentiation of 3T3-L1 preadipocytes to adipocytes in cells overexpressing wild type lamin A as well as lamin A with amino acid substitutions at position 482 that cause Dunnigan-type familial partial lipodystrophy. We also examined adipogenic conversion of mouse embryonic fibroblasts lacking A-type lamins. Overexpression of both wild type and mutant lamin A inhibited lipid accumulation, triglyceride synthesis and expression of adipogenic markers. This was associated with inhibition of expression of peroxisome proliferator activated receptor gamma 2 (PPAR{gamma}2) and Glut4. In contrast, embryonic fibroblasts lacking A-type lamins accumulated more intracellular lipid and exhibited elevated de novo triglyceride synthesis compared to wild type fibroblasts. They also had increased basal phosphorylation of AKT1, a mediator of insulin signaling. We conclude that A-type lamins act as inhibitors of adipocyte differentiation, possibly by affecting PPAR{gamma}2 and insulin signaling.


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