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

Title: A new role for lipocalin prostaglandin D synthase in the regulation of brown adipose tissue substrate utilization
Authors: Virtue, S
Feldmann, H
Christian, M
Tan, CY
Masoodi, M
Dale, M
Lelliott, C
Burling, K
Campbell, M
Eguchi, N
Voshol, P
Sethi, JK
Parker, M
Urade, Y
Griffin, JL
Cannon, B
Vidal-Puig, A
Item Type: Journal 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.
Issue Date: 1-Dec-2012
Date of Acceptance: 13-Jun-2012
URI: http://hdl.handle.net/10044/1/82227
DOI: 10.2337/db12-0015
ISSN: 0012-1797
Publisher: American Diabetes Association
Start Page: 3139
End Page: 3147
Journal / Book Title: Diabetes
Volume: 61
Issue: 12
Copyright Statement: © 2012 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by -nc-nd/3.0/ for details.
Keywords: Science & Technology
Life Sciences & Biomedicine
Endocrinology & Metabolism
COLD-EXPOSURE
GLUCOSE-UPTAKE
UNCOUPLING PROTEIN-1
SKELETAL-MUSCLE
ADULT HUMANS
RIP140
MICE
METABOLISM
EXPRESSION
OBESITY
Adipose Tissue, Brown
Animals
Body Composition
Cell Line
Female
Intramolecular Oxidoreductases
Lipocalins
Male
Mice
Real-Time Polymerase Chain Reaction
Thermogenesis
Triglycerides
Cell Line
Animals
Mice
Intramolecular Oxidoreductases
Triglycerides
Body Composition
Thermogenesis
Female
Male
Adipose Tissue, Brown
Lipocalins
Real-Time Polymerase Chain Reaction
Science & Technology
Life Sciences & Biomedicine
Endocrinology & Metabolism
COLD-EXPOSURE
GLUCOSE-UPTAKE
UNCOUPLING PROTEIN-1
SKELETAL-MUSCLE
ADULT HUMANS
RIP140
MICE
METABOLISM
EXPRESSION
OBESITY
Endocrinology & Metabolism
11 Medical and Health Sciences
Publication Status: Published
Online Publication Date: 2012-11-21
Appears in Collections:Department of Metabolism, Digestion and Reproduction



This item is licensed under a Creative Commons License Creative Commons