The University of Southampton
University of Southampton Institutional Repository

Lipocalin prostaglandin D synthase and PPARγ2 coordinate to regulate carbohydrate and lipid metabolism in vivo

Lipocalin prostaglandin D synthase and PPARγ2 coordinate to regulate carbohydrate and lipid metabolism in vivo
Lipocalin prostaglandin D synthase and PPARγ2 coordinate to regulate carbohydrate and lipid metabolism in vivo

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.

Adipocytes, Adipose Tissue, Brown, Adipose Tissue, White, Animals, Biomarkers, Carbohydrate Metabolism, Eicosanoids, Gene Expression Regulation, Insulin Resistance, Intramolecular Oxidoreductases, Lipid Metabolism, Lipocalins, Lipogenesis, Liver, Male, Mice, Mice, Knockout, PPAR gamma, RNA, Messenger, Subcutaneous Fat, Journal Article, Research Support, Non-U.S. Gov't
1932-6203
Virtue, Sam
5a5860ed-b7a9-4bee-a2cc-50a019b5bc5c
Masoodi, Mojgan
57584d36-e8d2-4c66-8e23-8bfa41be2382
Velagapudi, Vidya
826e06bc-e573-4725-a2f1-19c3acf15f5a
Tan, Chong Yew
7e1ea074-f229-4b76-a568-28cb5e63d289
Dale, Martin
9eb5db0d-9ef0-4391-9158-b37e04c621f2
Suorti, Tapani
c4a89230-6f29-497d-a762-462b76098065
Slawik, Marc
2fa28a50-9447-4875-bdd7-4b2be433f0c7
Blount, Margaret
23955494-af03-4a4d-a8bf-b1fb6ce9bb8c
Burling, Keith
b13b9066-e5e6-4f00-af1c-dab4f3567bd7
Campbell, Mark
ed49d284-9484-44c4-9bb0-5a661309e60f
Eguchi, Naomi
1ffaf8f8-ef45-47ff-ae3e-9eff32bae3a7
Medina-Gomez, Gema
9e8167bb-cfac-4bec-8e25-da1b42120e26
Sethi, Jaswinder K.
923f1a81-91e4-46cd-8853-bb4a979f5a85
Orešič, Matej
0238bcc4-1f43-4432-9586-da8a4ce781a4
Urade, Yoshihiro
9b5870b7-47e4-4988-8736-7ac86f7f9bb7
Griffin, Julian L.
efbf2925-ee1c-4e28-8e89-c1a70d143928
Vidal-Puig, Antonio
7d46d380-1b9d-40cb-90a3-72679e143036
Virtue, Sam
5a5860ed-b7a9-4bee-a2cc-50a019b5bc5c
Masoodi, Mojgan
57584d36-e8d2-4c66-8e23-8bfa41be2382
Velagapudi, Vidya
826e06bc-e573-4725-a2f1-19c3acf15f5a
Tan, Chong Yew
7e1ea074-f229-4b76-a568-28cb5e63d289
Dale, Martin
9eb5db0d-9ef0-4391-9158-b37e04c621f2
Suorti, Tapani
c4a89230-6f29-497d-a762-462b76098065
Slawik, Marc
2fa28a50-9447-4875-bdd7-4b2be433f0c7
Blount, Margaret
23955494-af03-4a4d-a8bf-b1fb6ce9bb8c
Burling, Keith
b13b9066-e5e6-4f00-af1c-dab4f3567bd7
Campbell, Mark
ed49d284-9484-44c4-9bb0-5a661309e60f
Eguchi, Naomi
1ffaf8f8-ef45-47ff-ae3e-9eff32bae3a7
Medina-Gomez, Gema
9e8167bb-cfac-4bec-8e25-da1b42120e26
Sethi, Jaswinder K.
923f1a81-91e4-46cd-8853-bb4a979f5a85
Orešič, Matej
0238bcc4-1f43-4432-9586-da8a4ce781a4
Urade, Yoshihiro
9b5870b7-47e4-4988-8736-7ac86f7f9bb7
Griffin, Julian L.
efbf2925-ee1c-4e28-8e89-c1a70d143928
Vidal-Puig, Antonio
7d46d380-1b9d-40cb-90a3-72679e143036

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., Orešič, Matej, Urade, Yoshihiro, Griffin, Julian L. and Vidal-Puig, Antonio (2012) Lipocalin prostaglandin D synthase and PPARγ2 coordinate to regulate carbohydrate and lipid metabolism in vivo. PLoS ONE, 7 (7), [e39512]. (doi:10.1371/journal.pone.0039512).

Record type: Article

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.

This record has no associated files available for download.

More information

Accepted/In Press date: 22 May 2012
e-pub ahead of print date: 5 July 2012
Published date: 5 July 2012
Keywords: Adipocytes, Adipose Tissue, Brown, Adipose Tissue, White, Animals, Biomarkers, Carbohydrate Metabolism, Eicosanoids, Gene Expression Regulation, Insulin Resistance, Intramolecular Oxidoreductases, Lipid Metabolism, Lipocalins, Lipogenesis, Liver, Male, Mice, Mice, Knockout, PPAR gamma, RNA, Messenger, Subcutaneous Fat, Journal Article, Research Support, Non-U.S. Gov't

Identifiers

Local EPrints ID: 415398
URI: http://eprints.soton.ac.uk/id/eprint/415398
ISSN: 1932-6203
PURE UUID: a71c6673-30c1-4408-a4e4-4818d424e025
ORCID for Jaswinder K. Sethi: ORCID iD orcid.org/0000-0003-4157-0475

Catalogue record

Date deposited: 09 Nov 2017 17:30
Last modified: 16 Mar 2024 04:31

Export record

Altmetrics

Contributors

Author: Sam Virtue
Author: Mojgan Masoodi
Author: Vidya Velagapudi
Author: Chong Yew Tan
Author: Martin Dale
Author: Tapani Suorti
Author: Marc Slawik
Author: Margaret Blount
Author: Keith Burling
Author: Mark Campbell
Author: Naomi Eguchi
Author: Gema Medina-Gomez
Author: Matej Orešič
Author: Yoshihiro Urade
Author: Julian L. Griffin
Author: Antonio Vidal-Puig

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×