title: Tissue-autonomous function of Drosophila seipin in preventing ectopic lipid droplet formation.
abstract: Obesity is characterized by accumulation of excess body fat, while lipodystrophy is characterized by loss or absence of body fat. Despite their opposite phenotypes, these two conditions both cause ectopic lipid storage in non-adipose tissues, leading to lipotoxicity, which has health-threatening consequences. The exact mechanisms underlying ectopic lipid storage remain elusive. Here we report the analysis of a Drosophila model of the most severe form of human lipodystrophy, Berardinelli-Seip Congenital Lipodystrophy 2, which is caused by mutations in the BSCL2/Seipin gene. In addition to reduced lipid storage in the fat body, dSeipin mutant flies accumulate ectopic lipid droplets in the salivary gland, a non-adipose tissue. This phenotype was suppressed by expressing dSeipin specifically within the salivary gland. dSeipin mutants display synergistic genetic interactions with lipogenic genes in the formation of ectopic lipid droplets. Our data suggest that dSeipin may participate in phosphatidic acid metabolism and subsequently down-regulate lipogenesis to prevent ectopic lipid droplet formation. In summary, we have demonstrated a tissue-autonomous role of dSeipin in ectopic lipid storage in lipodystrophy.
authors.affiliation: Key Laboratory of Molecular and Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Tian
authors.forename: Junfeng
authors.initials: J
authors.lastname: Bi
authors.forename: Guanghou
authors.initials: G
authors.lastname: Shui
authors.forename: Zhonghua
authors.initials: Z
authors.lastname: Liu
authors.forename: Yanhui
authors.initials: Y
authors.lastname: Xiang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Liu
authors.forename: Markus R
authors.initials: MR
authors.lastname: Wenk
authors.forename: Hongyuan
authors.initials: H
authors.lastname: Yang
authors.forename: Xun
authors.initials: X
authors.lastname: Huang
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004330:Drosophila / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D005216:Fat Body / Q000378:metabolism; D044388:GTP-Binding Protein gamma Subunits / Q000235:genetics* / Q000378:metabolism; D005822:Genetic Vectors; D007814:Larva / Q000254:growth & development / Q000378:metabolism; D008055:Lipids / Q000032:analysis*; D052497:Lipodystrophy, Congenital Generalized / Q000378:metabolism / Q000473:pathology; D050155:Lipogenesis; D008297:Male; D009154:Mutation; D009765:Obesity / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D010712:Phosphatidic Acids / Q000378:metabolism*; D034622:RNA Interference; D012469:Salivary Glands / Q000378:metabolism
chemical_list: D044388:GTP-Binding Protein gamma Subunits; D008055:Lipids; D010712:Phosphatidic Acids