Title

A Translational View of the Genetics of Lipodystrophy and Ectopic Fat Deposition

Document Type

Article

Publication Date

2010

Journal

Progress in Molecular Biology and Translational Science

Volume

94

First Page

159

Last Page

196

URL with Digital Object Identifier

http://dx.doi.org/10.1016/B978-0-12-375003-7.00006-6

Abstract

A wide range of lipodystrophy syndromes exist, each with varying clinical presentations, and yet cumulatively they underscore the importance of adipocyte biology in human metabolism. Loss of the ability to retain excess lipids in "classical" adipose tissue stores can lead to the overdevelopment of ectopic fat stores, often creating severe perturbations of both glucose and lipid homeostasis. Linkage analysis and candidate sequencing efforts have successfully identified responsible mutations for multiple forms of lipodystrophy. Recently, the reduction in the cost of DNA sequencing has resulted in discovery of many novel mutations within both known and novel loci. In this review, we present the steps involved in clinical characterization of a suspected lipodystrophy case, an overview of the clinical manifestations, molecular findings, and pathogenic basis of different forms of lipodystrophy, a discussion of therapeutic options for lipodystrophy patients, and an examination of genetic advances that will be used to identify additional pathogenic mechanisms.