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Cell autonomous lipin 1 function is essential for development and maintenance of white and brown adipose tissue.

Authors: Nadra, Karim  Médard, Jean-Jacques  Mul, Joram D  Han, Gil-Soo  Grès, Sandra  Pende, Mario  Metzger, Daniel  Chambon, Pierre  Cuppen, Edwin  Saulnier-Blache, Jean-Sébastien  Carman, George M  Desvergne, Béatrice  Chrast, Roman 
Citation: Nadra K, etal., Mol Cell Biol. 2012 Dec;32(23):4794-810. doi: 10.1128/MCB.00512-12. Epub 2012 Oct 1.
Pubmed: (View Article at PubMed) PMID:23028044
DOI: Full-text: DOI:10.1128/MCB.00512-12

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.

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RGD Object Information
RGD ID: 13673744
Created: 2018-06-23
Species: All species
Last Modified: 2018-06-23
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.