出版社：American Society for Biochemistry and Molecular Biology
摘要：The lipodystrophies are characterized by loss of adipose tissuein some anatomical sites, frequently with fat accumulation innonatrophic depots and ectopic sites such as liver and muscle.Molecularly characterized forms include Dunnigan-type familialpartial lipodystrophy (FPLD), partial lipodystrophy with mandibuloacraldysplasia (MAD), Berardinelli-Seip congenital generalized lipodystrophy(CGL), and some cases with Barraquer-Simons acquired partiallipodystrophy (APL). The associated mutant gene products include1) nuclear lamin A in FPLD type 2 and MAD type A; 2) nuclearlamin B2 in APL; 3) nuclear hormone receptor peroxisome proliferator-activatedreceptor in FPLD type 3; 4) lipid biosynthetic enzyme 1-acylglycerol-3-phosphateO-acyltransferase 2 in CGL type 1; 5) integral endoplasmic reticulummembrane protein seipin in CGL type 2; and 6) metalloproteinaseZMPSTE24 in MAD type B. An unresolved question is whether metabolicdisturbances are secondary to adipose repartitioning or resultfrom a direct effect of the mutant gene product. Careful analysisof clinical, biochemical, and imaging phenotypes, using an approachcalled "phenomics," reveals differences between geneticallystratified subtypes that can be used to guide basic experimentsand to improve our understanding of common clinical entities,such as metabolic syndrome or the partial lipodystrophy syndromeassociated with human immunodeficiency virus infection.Supplementary key words fatty acid • metabolism • obesity • type 2 diabetes • insulin resistance • dyslipidemia • genetics • medical imaging • laminopathy • nuclear hormone receptors
in FPLD type 3; 4) lipid biosynthetic enzyme 1-acylglycerol-3-phosphate O-acyltransferase 2 in CGL type 1; 5) integral endoplasmic reticulum membrane protein seipin in CGL type 2; and 6) metalloproteinase ZMPSTE24 in MAD type B. An unresolved question is whether metabolic disturbances are secondary to adipose repartitioning or result from a direct effect of the mutant gene product. Careful analysis of clinical, biochemical, and imaging phenotypes, using an approach called "phenomics," reveals differences between genetically stratified subtypes that can be used to guide basic experiments and to improve our understanding of common clinical entities, such as metabolic syndrome or the partial lipodystrophy syndrome associated with human immunodeficiency virus infection.
Supplementary key words fatty acid • metabolism • obesity • type 2 diabetes • insulin resistance • dyslipidemia • genetics • medical imaging • laminopathy • nuclear hormone receptors
