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A new role for lipocalin prostaglandin D synthase in the regulation of brown adipose tissue substrate utilization

A new role for lipocalin prostaglandin D synthase in the regulation of brown adipose tissue substrate utilization
A new role for lipocalin prostaglandin D synthase in the regulation of brown adipose tissue substrate utilization

In this study, we define a new role for lipocalin prostaglandin D synthase (L-PGDS) in the control of metabolic fuel utilization by brown adipose tissue (BAT). We demonstrate that L-PGDS expression in BAT is positively correlated with BAT activity, upregulated by peroxisome proliferator-activated receptor γ coactivator 1α or 1β and repressed by receptor-interacting protein 140. Under cold-acclimated conditions, mice lacking L-PGDS had elevated reliance on carbohydrate to provide fuel for thermogenesis and had increased expression of genes regulating glycolysis and de novo lipogenesis in BAT. These transcriptional differences were associated with increased lipid content in BAT and a BAT lipid composition enriched with de novo synthesized lipids. Consistent with the concept that lack of L-PGDS increases glucose utilization, mice lacking L-PGDS had improved glucose tolerance after high-fat feeding. The improved glucose tolerance appeared to be independent of changes in insulin sensitivity, as insulin levels during the glucose tolerance test and insulin, leptin, and adiponectin levels were unchanged. Moreover, L-PGDS knockout mice exhibited increased expression of genes involved in thermogenesis and increased norepinephrine-stimulated glucose uptake to BAT, suggesting that sympathetically mediated changes in glucose uptake may have improved glucose tolerance. Taken together, these results suggest that L-PGDS plays an important role in the regulation of glucose utilization in vivo.

Adipose Tissue, Brown, Animals, Body Composition, Cell Line, Female, Intramolecular Oxidoreductases, Lipocalins, Male, Mice, Real-Time Polymerase Chain Reaction, Thermogenesis, Triglycerides, Journal Article, Research Support, Non-U.S. Gov't
0012-1797
3139-47
Virtue, Sam
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Feldmann, Helena
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Christian, Mark
e267db8a-574a-4468-b545-51bcfdfc51c2
Tan, Chong Yew
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Masoodi, Mojgan
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Dale, Martin
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Lelliott, Chris
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Burling, Keith
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Campbell, Mark
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Eguchi, Naomi
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Voshol, Peter
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Sethi, Jaswinder K.
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Parker, Malcolm
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Urade, Yoshihiro
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Griffin, Julian L
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Cannon, Barbara
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Vidal-Puig, Antonio
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Virtue, Sam
5a5860ed-b7a9-4bee-a2cc-50a019b5bc5c
Feldmann, Helena
70fcd989-288c-48a4-8b22-91d3c7f9d686
Christian, Mark
e267db8a-574a-4468-b545-51bcfdfc51c2
Tan, Chong Yew
7e1ea074-f229-4b76-a568-28cb5e63d289
Masoodi, Mojgan
57584d36-e8d2-4c66-8e23-8bfa41be2382
Dale, Martin
9eb5db0d-9ef0-4391-9158-b37e04c621f2
Lelliott, Chris
eebf4823-ee2f-47f7-9122-3d49883bbb61
Burling, Keith
b13b9066-e5e6-4f00-af1c-dab4f3567bd7
Campbell, Mark
ed49d284-9484-44c4-9bb0-5a661309e60f
Eguchi, Naomi
1ffaf8f8-ef45-47ff-ae3e-9eff32bae3a7
Voshol, Peter
167e770e-807f-4d0d-af37-f8fa85bca772
Sethi, Jaswinder K.
923f1a81-91e4-46cd-8853-bb4a979f5a85
Parker, Malcolm
ff9fc9bc-a8bd-4cab-b288-457f83ec4cd2
Urade, Yoshihiro
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Griffin, Julian L
efbf2925-ee1c-4e28-8e89-c1a70d143928
Cannon, Barbara
cd7fe7a5-5aca-4dcb-b6ae-d60d0da94ed9
Vidal-Puig, Antonio
7d46d380-1b9d-40cb-90a3-72679e143036

Virtue, Sam, Feldmann, Helena, Christian, Mark, Tan, Chong Yew, Masoodi, Mojgan, Dale, Martin, Lelliott, Chris, Burling, Keith, Campbell, Mark, Eguchi, Naomi, Voshol, Peter, Sethi, Jaswinder K., Parker, Malcolm, Urade, Yoshihiro, Griffin, Julian L, Cannon, Barbara and Vidal-Puig, Antonio (2012) A new role for lipocalin prostaglandin D synthase in the regulation of brown adipose tissue substrate utilization. Diabetes, 61 (12), 3139-47. (doi:10.2337/db12-0015).

Record type: Article

Abstract

In this study, we define a new role for lipocalin prostaglandin D synthase (L-PGDS) in the control of metabolic fuel utilization by brown adipose tissue (BAT). We demonstrate that L-PGDS expression in BAT is positively correlated with BAT activity, upregulated by peroxisome proliferator-activated receptor γ coactivator 1α or 1β and repressed by receptor-interacting protein 140. Under cold-acclimated conditions, mice lacking L-PGDS had elevated reliance on carbohydrate to provide fuel for thermogenesis and had increased expression of genes regulating glycolysis and de novo lipogenesis in BAT. These transcriptional differences were associated with increased lipid content in BAT and a BAT lipid composition enriched with de novo synthesized lipids. Consistent with the concept that lack of L-PGDS increases glucose utilization, mice lacking L-PGDS had improved glucose tolerance after high-fat feeding. The improved glucose tolerance appeared to be independent of changes in insulin sensitivity, as insulin levels during the glucose tolerance test and insulin, leptin, and adiponectin levels were unchanged. Moreover, L-PGDS knockout mice exhibited increased expression of genes involved in thermogenesis and increased norepinephrine-stimulated glucose uptake to BAT, suggesting that sympathetically mediated changes in glucose uptake may have improved glucose tolerance. Taken together, these results suggest that L-PGDS plays an important role in the regulation of glucose utilization in vivo.

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More information

Accepted/In Press date: 13 June 2012
e-pub ahead of print date: 24 August 2012
Published date: December 2012
Keywords: Adipose Tissue, Brown, Animals, Body Composition, Cell Line, Female, Intramolecular Oxidoreductases, Lipocalins, Male, Mice, Real-Time Polymerase Chain Reaction, Thermogenesis, Triglycerides, Journal Article, Research Support, Non-U.S. Gov't

Identifiers

Local EPrints ID: 415397
URI: http://eprints.soton.ac.uk/id/eprint/415397
ISSN: 0012-1797
PURE UUID: dfc0b03f-3e17-4aba-9b34-916db65e4b47
ORCID for Jaswinder K. Sethi: ORCID iD orcid.org/0000-0003-4157-0475

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

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Contributors

Author: Sam Virtue
Author: Helena Feldmann
Author: Mark Christian
Author: Chong Yew Tan
Author: Mojgan Masoodi
Author: Martin Dale
Author: Chris Lelliott
Author: Keith Burling
Author: Mark Campbell
Author: Naomi Eguchi
Author: Peter Voshol
Author: Malcolm Parker
Author: Yoshihiro Urade
Author: Julian L Griffin
Author: Barbara Cannon
Author: Antonio Vidal-Puig

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