title: Perilipin deficiency and autosomal dominant partial lipodystrophy.
abstract: Perilipin is the most abundant adipocyte-specific protein that coats lipid droplets, and it is required for optimal lipid incorporation and release from the droplet. We identified two heterozygous frameshift mutations in the perilipin gene (PLIN1) in three families with partial lipodystrophy, severe dyslipidemia, and insulin-resistant diabetes. Subcutaneous fat from the patients was characterized by smaller-than-normal adipocytes, macrophage infiltration, and fibrosis. In contrast to wild-type perilipin, mutant forms of the protein failed to increase triglyceride accumulation when expressed heterologously in preadipocytes. These findings define a novel dominant form of inherited lipodystrophy and highlight the serious metabolic consequences of a primary defect in the formation of lipid droplets in adipose tissue.
authors.affiliation: University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, United Kingdom.
authors.forename: Sheetal
authors.initials: S
authors.lastname: Gandotra
authors.forename: Caroline
authors.initials: C
authors.lastname: Le Dour
authors.forename: William
authors.initials: W
authors.lastname: Bottomley
authors.forename: Pascale
authors.initials: P
authors.lastname: Cervera
authors.forename: Philippe
authors.initials: P
authors.lastname: Giral
authors.forename: Yves
authors.initials: Y
authors.lastname: Reznik
authors.forename: Guillaume
authors.initials: G
authors.lastname: Charpentier
authors.forename: Martine
authors.initials: M
authors.lastname: Auclair
authors.forename: Marc
authors.initials: M
authors.lastname: Delépine
authors.forename: Inês
authors.initials: I
authors.lastname: Barroso
authors.forename: Robert K
authors.initials: RK
authors.lastname: Semple
authors.forename: Mark
authors.initials: M
authors.lastname: Lathrop
authors.forename: Olivier
authors.initials: O
authors.lastname: Lascols
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Capeau
authors.forename: Stephen
authors.initials: S
authors.lastname: O'Rahilly
authors.forename: Jocelyne
authors.initials: J
authors.lastname: Magré
authors.forename: David B
authors.initials: DB
authors.lastname: Savage
authors.forename: Corinne
authors.initials: C
authors.lastname: Vigouroux
mesh_terms: D000052:Acanthosis Nigricans / Q000235:genetics; D000328:Adult; D002352:Carrier Proteins; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D005260:Female; D016368:Frameshift Mutation; D005799:Genes, Dominant; D006579:Heterozygote; D006801:Humans; D015228:Hypertriglyceridemia / Q000235:genetics*; D007333:Insulin Resistance / Q000235:genetics; D052496:Lipodystrophy, Familial Partial / Q000235:genetics*; D008875:Middle Aged; D010375:Pedigree; D000070778:Perilipin-1; D010750:Phosphoproteins / Q000172:deficiency* / Q000235:genetics*
chemical_list: D002352:Carrier Proteins; C000602978:PLIN1 protein, human; D000070778:Perilipin-1; D010750:Phosphoproteins