Genetic basis of lipodystrophies and management of metabolic complications.
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.
Agarwal
Anil K
AK
Division of Nutrition and Metabolic Diseases, Department of Internal Medicine and the Center for Human Nutrition, The University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390-9052, USA.
Garg
Abhimanyu
A
D051103:1-Acylglycerol-3-Phosphate O-Acyltransferase / Q000235:genetics; D044388:GTP-Binding Protein gamma Subunits / Q000235:genetics; D006801:Humans; D034904:Lamin Type A / Q000235:genetics; D008060:Lipodystrophy / Q000150:complications / Q000235:genetics* / Q000628:therapy*; D008074:Lipoproteins / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics; D008666:Metalloendopeptidases; D045726:Metalloproteases / Q000235:genetics; D047495:PPAR gamma / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics
C432679:BSCL2 protein, human; D044388:GTP-Binding Protein gamma Subunits; C494847:LMNA protein, human; D034904:Lamin Type A; D008074:Lipoproteins; D008565:Membrane Proteins; D047495:PPAR gamma; D051103:1-Acylglycerol-3-Phosphate O-Acyltransferase; C494921:AKT2 protein, human; D051057:Proto-Oncogene Proteins c-akt; D045726:Metalloproteases; D008666:Metalloendopeptidases; C120130:ZMPSTE24 protein, human