Genetic basis of lipodystrophies and management of metabolic complications

Annu Rev Med. 2006;57:297-311. doi: 10.1146/


Selective loss of body fat is the hallmark of patients with lipodystrophies. Among genetic lipodystrophies, fat loss is observed either from birth, as in congenital generalized lipodystrophy, or later in life, as in familial partial lipodystrophy. The extent of fat loss also varies among subtypes of lipodystrophies. Patients develop hyperinsulinemia, acanthosis nigricans, hypertriglyceridemia, diabetes mellitus, and hepatic steatosis. Defects in several genes, such as those encoding an enzyme (AGPAT2), a nuclear receptor (PPARgamma), a nuclear lamina protein (LMNA) and its processing endoprotease (ZMPSTE24), a kinase (AKT2), and a protein of unknown function (BSCL2), have been found in patients with genetic lipodystrophies. Additional loci remain to be discovered. We discuss features of autosomal recessive and dominant types of lipodystrophies and therapeutic interventions available for these patients.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • 1-Acylglycerol-3-Phosphate O-Acyltransferase / genetics
  • GTP-Binding Protein gamma Subunits / genetics
  • Humans
  • Lamin Type A / genetics
  • Lipodystrophy / complications
  • Lipodystrophy / genetics*
  • Lipodystrophy / therapy*
  • Lipoproteins / genetics
  • Membrane Proteins / genetics
  • Metalloendopeptidases
  • Metalloproteases / genetics
  • PPAR gamma / genetics
  • Proto-Oncogene Proteins c-akt / genetics


  • BSCL2 protein, human
  • GTP-Binding Protein gamma Subunits
  • LMNA protein, human
  • Lamin Type A
  • Lipoproteins
  • Membrane Proteins
  • PPAR gamma
  • 1-Acylglycerol-3-Phosphate O-Acyltransferase
  • AKT2 protein, human
  • Proto-Oncogene Proteins c-akt
  • Metalloproteases
  • Metalloendopeptidases
  • ZMPSTE24 protein, human