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

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Title: Lipocalin prostaglandin D synthase and PPARγ2 coordinate to regulate carbohydrate and lipid metabolism in vivo
Authors: Virtue, S
Masoodi, M
Velagapudi, V
Tan, CY
Dale, M
Suorti, 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
Item Type: Journal 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.
Issue Date: 5-Jul-2012
Date of Acceptance: 22-May-2012
URI: http://hdl.handle.net/10044/1/81793
DOI: 10.1371/journal.pone.0039512
ISSN: 1932-6203
Publisher: Public Library of Science (PLoS)
Journal / Book Title: PLoS One
Volume: 7
Issue: 7
Copyright Statement: © 2012 Virtue et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permitsunrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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
Liver
Adipocytes
Animals
Mice, Knockout
Mice
Insulin Resistance
Intramolecular Oxidoreductases
Eicosanoids
PPAR gamma
RNA, Messenger
Gene Expression Regulation
Male
Subcutaneous Fat
Lipogenesis
Carbohydrate Metabolism
Lipid Metabolism
Adipose Tissue, Brown
Adipose Tissue, White
Lipocalins
Biomarkers
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
General Science & Technology
Publication Status: Published
Conference Place: United States
Article Number: ARTN e39512
Appears in Collections:Department of Metabolism, Digestion and Reproduction



This item is licensed under a Creative Commons License Creative Commons