| Autor: |
Virtue, Sam, Masoodi, Mojgan, Velagapudi, Vidya, Chong Yew Tan, Dale, Martin, Suorti, Tapani, Slawik, Marc, Blount, Margaret, Burling, Keith, Campbell, Mark, Eguchi, Naomi, Medina-Gomez, Gema, Sethi, Jaswinder K., Orešic, Matej, Urade, Yoshihiro, Griffin, Julian L., Vidal-Puig, Antonio |
| Předmět: |
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| Zdroj: |
PLoS ONE; Jul2012, Vol. 7 Issue 7, p1-12, 12p |
| Abstrakt: |
Mice lacking Peroxisome Proliferator-Activated Receptor Υ2 (PPARΥ2) have unexpectedly normal glucose tolerance and mild insulin resistance. Mice lacking PPARΥ2 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 PPARΥ2, we crossed L-PGDS KO mice to PPARΥ2 KO mice to generate Double Knock Out mice (DKO). Using DKO mice we demonstrated a requirement of L-PGDS for maintenance of subcutaneous WAT (sΥWAT) 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 PPARΥ2 coordinate to regulate carbohydrate and lipid metabolism. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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