Lipocalin Prostaglandin D Synthase and PPAR[gamma]2 Coordinate to Regulate Carbohydrate and Lipid Metabolism In Vivo

Mice lacking Peroxisome Proliferator-Activated Receptor [gamma]2 (PPAR[gamma]2) have unexpectedly normal glucose tolerance and mild insulin resistance. Mice lacking PPAR[gamma]2 were found to have elevated levels of Lipocalin prostaglandin D synthase (L-PGDS) expression in BAT and subcutaneous white...

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Published in:PloS one 2012-07, Vol.7 (7), p.e39512
Main Authors: Virtue, Sam, Masoodi, Mojgan, Velagapudi, Vidya, Tan, Chong Yew, Dale, Martin, Suorti, Tapani, Slawik, Marc, Blount, Margaret, Burling, Keith, Campbell, Mark, Eguchi, Naomi, Medina-Gomez, Gema, Sethi, Jaswinder K, Oresic, Matej, Urade, Yoshihiro, Griffin, Julian L, Vidal-Puig, Antonio
Format: Article
Language:English
Subjects:
Adipose tissue
Carbohydrate metabolism
Glucose
Insulin resistance
Lipase
Physiological aspects
Prostaglandins
Triglycerides
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Summary:Mice lacking Peroxisome Proliferator-Activated Receptor [gamma]2 (PPAR[gamma]2) have unexpectedly normal glucose tolerance and mild insulin resistance. Mice lacking PPAR[gamma]2 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 PPAR[gamma]2, we crossed L-PGDS KO mice to PPAR[gamma]2 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 PPAR[gamma]2 coordinate to regulate carbohydrate and lipid metabolism.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0039512