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)

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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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prostaglandin R2 D-isomerase
Lipocalins
Peroxisome Proliferator-Activated Receptors
Carbohydrate Metabolism
carbohydrate metabolism
Lipid Metabolism
lipid metabolism
White Adipose Tissue
Tissue
Knockout Mice
mice
white adipose tissue
Intra-Abdominal Fat
Lipolysis
Subcutaneous Fat
Glucose
Lipase
peroxisome proliferator-activated receptors
prostaglandin-D synthase
Triglycerides

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Virtue, S., Masoodi, M., Velagapudi, V., Tan, C. Y., Dale, M., Suortti, T., ... Vidal-Puig, A. (2012). Lipocalin Prostaglandin D Synthase and PPARγ2 Coordinate to Regulate Carbohydrate and Lipid Metabolism In Vivo. PLoS ONE, 7(7), [e39512]. https://doi.org/10.1371/journal.pone.0039512
Virtue, Sam ; Masoodi, Mojgan ; Velagapudi, Vidya ; Tan, Chong Yew ; Dale, Martin ; Suortti, Tapani ; Slawik, Marc ; Blount, Margaret ; Burling, Keith ; Campbell, Mark ; Eguchi, Naomi ; Medina-Gomez, Gema ; Sethi, Jaswinder K. ; Orešič, Matej ; Urade, Yoshihiro ; Griffin, Julian L. ; Vidal-Puig, Antonio. / Lipocalin Prostaglandin D Synthase and PPARγ2 Coordinate to Regulate Carbohydrate and Lipid Metabolism In Vivo. In: PLoS ONE. 2012 ; Vol. 7, No. 7.
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title = "Lipocalin Prostaglandin D Synthase and PPARγ2 Coordinate to Regulate Carbohydrate and Lipid Metabolism In Vivo",
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.",
author = "Sam Virtue and Mojgan Masoodi and Vidya Velagapudi and Tan, {Chong Yew} and Martin Dale and Tapani Suortti and Marc Slawik and Margaret Blount and Keith Burling and Mark Campbell and Naomi Eguchi and Gema Medina-Gomez and Sethi, {Jaswinder K.} and Matej Orešič and Yoshihiro Urade and Griffin, {Julian L.} and Antonio Vidal-Puig",
year = "2012",
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Virtue, S, Masoodi, M, Velagapudi, V, Tan, CY, Dale, M, Suortti, T, Slawik, M, Blount, M, Burling, K, Campbell, M, Eguchi, N, Medina-Gomez, G, Sethi, JK, Orešič, M, Urade, Y, Griffin, JL & Vidal-Puig, A 2012, 'Lipocalin Prostaglandin D Synthase and PPARγ2 Coordinate to Regulate Carbohydrate and Lipid Metabolism In Vivo', PLoS ONE, vol. 7, no. 7, e39512. https://doi.org/10.1371/journal.pone.0039512

Lipocalin Prostaglandin D Synthase and PPARγ2 Coordinate to Regulate Carbohydrate and Lipid Metabolism In Vivo. / Virtue, Sam (Corresponding Author); Masoodi, Mojgan; Velagapudi, Vidya; Tan, Chong Yew; Dale, Martin; Suortti, Tapani; Slawik, Marc; Blount, Margaret; Burling, Keith; Campbell, Mark; Eguchi, Naomi; Medina-Gomez, Gema; Sethi, Jaswinder K.; Orešič, Matej; Urade, Yoshihiro; Griffin, Julian L.; Vidal-Puig, Antonio (Corresponding Author).

In: PLoS ONE, Vol. 7, No. 7, e39512, 2012.

Research output: Contribution to journalArticleScientificpeer-review

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T1 - Lipocalin Prostaglandin D Synthase and PPARγ2 Coordinate to Regulate Carbohydrate and Lipid Metabolism In Vivo

AU - Virtue, Sam

AU - Masoodi, Mojgan

AU - Velagapudi, Vidya

AU - Tan, Chong Yew

AU - Dale, Martin

AU - Suortti, Tapani

AU - Slawik, Marc

AU - Blount, Margaret

AU - Burling, Keith

AU - Campbell, Mark

AU - Eguchi, Naomi

AU - Medina-Gomez, Gema

AU - Sethi, Jaswinder K.

AU - Orešič, Matej

AU - Urade, Yoshihiro

AU - Griffin, Julian L.

AU - Vidal-Puig, Antonio

PY - 2012

Y1 - 2012

N2 - 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.

AB - 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.

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DO - 10.1371/journal.pone.0039512

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