title: Perilipin overexpression in white adipose tissue induces a brown fat-like phenotype.
abstract: BACKGROUND
  Perilipin A (PeriA) exclusively locates on adipocyte lipid droplets and is essential for lipid storage and lipolysis. Previously, we reported that adipocyte specific overexpression of PeriA caused resistance to diet-induced obesity and resulted in improved insulin sensitivity. In order to better understand the biological basis for this observed phenotype, we performed additional studies in this transgenic mouse model.
  
  
  RESULTS
  When compared to control animals, whole body energy expenditure was increased in the transgenic mice. Subsequently, we performed DNA microarray analysis and real-time PCR on white adipose tissue. Consistent with the metabolic chamber data, we observed increased expression of genes associated with fatty acid β-oxidation and heat production, and a decrease in the genes associated with lipid synthesis. Gene expression of Pgc1a, a regulator of fatty acid oxidation and Ucp1, a brown adipocyte specific protein, was increased in the white adipose tissue of the transgenic mice. This observation was subsequently verified by both Western blotting and histological examination. Expression of RIP140, a regulator of white adipocyte differentiation, and the lipid droplet protein FSP27 was decreased in the transgenic mice. Importantly, FSP27 has been shown to control gene expression of these crucial metabolic regulators. Overexpression of PeriA in 3T3-L1 adipocytes also reduced FSP27 expression and diminished lipid droplet size.
  
  
  CONCLUSIONS
  These findings demonstrate that overexpression of PeriA in white adipocytes reduces lipid droplet size by decreasing FSP27 expression and thereby inducing a brown adipose tissue-like phenotype. Our data suggest that modulation of lipid droplet proteins in white adipocytes is a potential therapeutic strategy for the treatment of obesity and its related disorders.
authors.affiliation: Department of Internal Medicine II, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Sawada
authors.forename: Hideaki
authors.initials: H
authors.lastname: Miyoshi
authors.forename: Kohei
authors.initials: K
authors.lastname: Shimada
authors.forename: Akira
authors.initials: A
authors.lastname: Suzuki
authors.forename: Yuko
authors.initials: Y
authors.lastname: Okamatsu-Ogura
authors.forename: James W
authors.initials: JW
authors.lastname: Perfield
authors.forename: Takuma
authors.initials: T
authors.lastname: Kondo
authors.forename: So
authors.initials: S
authors.lastname: Nagai
authors.forename: Chikara
authors.initials: C
authors.lastname: Shimizu
authors.forename: Narihito
authors.initials: N
authors.lastname: Yoshioka
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Greenberg
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kimura
authors.forename: Takao
authors.initials: T
authors.lastname: Koike
mesh_terms: D041721:3T3-L1 Cells; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D002001:Adipose Tissue, Brown / Q000378:metabolism*; D052436:Adipose Tissue, White / Q000378:metabolism*; D000818:Animals; D002352:Carrier Proteins; D004734:Energy Metabolism; D005227:Fatty Acids / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D000078723:Nuclear Receptor Interacting Protein 1; D020411:Oligonucleotide Array Sequence Analysis; D010101:Oxygen Consumption; D000070778:Perilipin-1; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors; D014162:Transfection; D000071256:Uncoupling Protein 1
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D005227:Fatty Acids; D007473:Ion Channels; D024101:Mitochondrial Proteins; C000627127:NRIP1 protein, human; D009687:Nuclear Proteins; D000078723:Nuclear Receptor Interacting Protein 1; D000070778:Perilipin-1; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010750:Phosphoproteins; C485290:Ppargc1a protein, mouse; D011506:Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C000604371:UCP1 protein, human; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1; C525805:fat-specific protein 27, mouse