title: The role of LMNA in adipose: a novel mouse model of lipodystrophy based on the Dunnigan-type familial partial lipodystrophy mutation.
abstract: We investigated the role of LMNA in adipose tissue by developing a novel mouse model of lipodystrophy. Transgenic mice were generated that express the LMNA mutation that causes familial partial lipodystrophy of the Dunnigan type (FPLD2). The phenotype observed in FPLD-transgenic mice resembles many of the features of human FPLD2, including lack of fat accumulation, insulin resistance, and enlarged, fatty liver. Similar to the human disease, FPLD-transgenic mice appear to develop normally, but after several weeks they are unable to accumulate fat to the same extent as their wild-type littermates. One poorly understood aspect of lipodystrophies is the mechanism of fat loss. To this end, we have examined the effects of the FPLD2 mutation on fat cell function. Contrary to the current literature, which suggests FPLD2 results in a loss of fat, we found that the key mechanism contributing to the lack of fat accumulation involves not a loss, but an apparent inability of the adipose tissue to renew itself. Specifically, preadipocytes are unable to differentiate into mature and fully functional adipocytes. These findings provide insights not only for the treatment of lipodystrophies, but also for the study of adipogenesis, obesity, and insulin resistance.
authors.affiliation: Laboratory of Cellular and Developmental Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA. wojtanikk@niddk.nih.gov
authors.forename: Kari M
authors.initials: KM
authors.lastname: Wojtanik
authors.forename: Keith
authors.initials: K
authors.lastname: Edgemon
authors.forename: Srikant
authors.initials: S
authors.lastname: Viswanadha
authors.forename: Brigette
authors.initials: B
authors.lastname: Lindsey
authors.forename: Martin
authors.initials: M
authors.lastname: Haluzik
authors.forename: Weiping
authors.initials: W
authors.lastname: Chen
authors.forename: George
authors.initials: G
authors.lastname: Poy
authors.forename: Marc
authors.initials: M
authors.lastname: Reitman
authors.forename: Constantine
authors.initials: C
authors.lastname: Londos
mesh_terms: D017667:Adipocytes / Q000378:metabolism / Q000473:pathology; D000273:Adipose Tissue / Q000378:metabolism* / Q000473:pathology; D002001:Adipose Tissue, Brown / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation; D017931:DNA Primers / Q000235:genetics; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics / Q000502:physiology; D034904:Lamin Type A / Q000235:genetics* / Q000378:metabolism*; D052496:Lipodystrophy, Familial Partial / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D008066:Lipolysis / Q000235:genetics / Q000502:physiology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D010641:Phenotype; D022722:Thermogenesis / Q000235:genetics / Q000502:physiology
chemical_list: D017931:DNA Primers; C494847:LMNA protein, human; D034904:Lamin Type A