title: Cell autonomous lipin 1 function is essential for development and maintenance of white and brown adipose tissue.
abstract: Through analysis of mice with spatially and temporally restricted inactivation of Lpin1, we characterized its cell autonomous function in both white (WAT) and brown (BAT) adipocyte development and maintenance. We observed that the lipin 1 inactivation in adipocytes of aP2(Cre/+)/Lp(fEx2)(-)(3/fEx2)(-)(3) mice resulted in lipodystrophy and the presence of adipocytes with multilocular lipid droplets. We further showed that time-specific loss of lipin 1 in mature adipocytes in aP2(Cre-ERT2/+)/Lp(fEx2)(-)(3/fEx2)(-)(3) mice led to their replacement by newly formed Lpin1-positive adipocytes, thus establishing a role for lipin 1 in mature adipocyte maintenance. Importantly, we observed that the presence of newly formed Lpin1-positive adipocytes in aP2(Cre-ERT2/+)/Lp(fEx2)(-)(3/fEx2)(-)(3) mice protected these animals against WAT inflammation and hepatic steatosis induced by a high-fat diet. Loss of lipin 1 also affected BAT development and function, as revealed by histological changes, defects in the expression of peroxisome proliferator-activated receptor alpha (PPARα), PGC-1α, and UCP1, and functionally by altered cold sensitivity. Finally, our data indicate that phosphatidic acid, which accumulates in WAT of animals lacking lipin 1 function, specifically inhibits differentiation of preadipocytes. Together, these observations firmly demonstrate a cell autonomous role of lipin 1 in WAT and BAT biology and indicate its potential as a therapeutical target for the treatment of obesity.
authors.affiliation: Department of Medical Genetics, University of Lausanne, Lausanne, Switzerland.
authors.forename: Karim
authors.initials: K
authors.lastname: Nadra
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Médard
authors.forename: Joram D
authors.initials: JD
authors.lastname: Mul
authors.forename: Gil-Soo
authors.initials: GS
authors.lastname: Han
authors.forename: Sandra
authors.initials: S
authors.lastname: Grès
authors.forename: Mario
authors.initials: M
authors.lastname: Pende
authors.forename: Daniel
authors.initials: D
authors.lastname: Metzger
authors.forename: Pierre
authors.initials: P
authors.lastname: Chambon
authors.forename: Edwin
authors.initials: E
authors.lastname: Cuppen
authors.forename: Jean-Sébastien
authors.initials: JS
authors.lastname: Saulnier-Blache
authors.forename: George M
authors.initials: GM
authors.lastname: Carman
authors.forename: Béatrice
authors.initials: B
authors.lastname: Desvergne
authors.forename: Roman
authors.initials: R
authors.lastname: Chrast
mesh_terms: D016475:3T3 Cells; D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism*; D002001:Adipose Tissue, Brown / Q000166:cytology* / Q000378:metabolism; D052436:Adipose Tissue, White / Q000166:cytology* / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D002478:Cells, Cultured; D059305:Diet, High-Fat / Q000009:adverse effects; D017353:Gene Deletion; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D009765:Obesity / Q000235:genetics / Q000378:metabolism; D010711:Phosphatidate Phosphatase / Q000235:genetics / Q000378:metabolism*; D010712:Phosphatidic Acids / Q000378:metabolism
chemical_list: D009687:Nuclear Proteins; D010712:Phosphatidic Acids; C418978:Lpin1 protein, mouse; D010711:Phosphatidate Phosphatase