Lipocalin Prostaglandin D Synthase and PPARγ2 Coordinate to Regulate Carbohydrate and Lipid Metabolism In Vivo

Sam Virtue (Corresponding Author), Mojgan Masoodi, Vidya Velagapudi, Chong Yew Tan, Martin Dale, Tapani Suortti, Marc Slawik, Margaret Blount, Keith Burling, Mark Campbell, Naomi Eguchi, Gema Medina-Gomez, Jaswinder K. Sethi, Matej Orešič, Yoshihiro Urade, Julian L. Griffin, Antonio Vidal-Puig (Corresponding Author)

Research output: Contribution to journalArticleScientificpeer-review

12 Citations (Scopus)

Abstract

Mice lacking Peroxisome Proliferator-Activated Receptor γ2 (PPARγ2) have unexpectedly normal glucose tolerance and mild insulin resistance. Mice lacking PPARγ2 were found to have elevated levels of Lipocalin prostaglandin D synthase (L-PGDS) expression in BAT and subcutaneous white adipose tissue (WAT). To determine if induction of L-PGDS was compensating for a lack of PPARγ2, we crossed L-PGDS KO mice to PPARγ2 KO mice to generate Double Knock Out mice (DKO). Using DKO mice we demonstrated a requirement of L-PGDS for maintenance of subcutaneous WAT (scWAT) function. In scWAT, DKO mice had reduced expression of thermogenic genes, the de novo lipogenic program and the lipases ATGL and HSL. Despite the reduction in markers of lipolysis in scWAT, DKO mice had a normal metabolic rate and elevated serum FFA levels compared to L-PGDS KO alone. Analysis of intra-abdominal white adipose tissue (epididymal WAT) showed elevated expression of mRNA and protein markers of lipolysis in DKO mice, suggesting that DKO mice may become more reliant on intra-abdominal WAT to supply lipid for oxidation. This switch in depot utilisation from subcutaneous to epididymal white adipose tissue was associated with a worsening of whole organism metabolic function, with DKO mice being glucose intolerant, and having elevated serum triglyceride levels compared to any other genotype. Overall, L-PGDS and PPARγ2 coordinate to regulate carbohydrate and lipid metabolism.
Original languageEnglish
Article numbere39512
JournalPLoS ONE
Volume7
Issue number7
DOIs
Publication statusPublished - 2012
MoE publication typeA1 Journal article-refereed

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