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Lipocalin prostaglandin D synthase and PPARγ2 coordinate to regulate carbohydrate and lipid metabolism in vivo
University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Cambridge, United Kingdom.
Elsie Widdowson Laboratory, Medical Research Council Human Nutrition Research, Cambridge, United Kingdom.
VTT Technical Research Centre of Finland, Espoo, Finland.
University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Cambridge, United Kingdom.
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2012 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, no 7, article id e39512Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2012. Vol. 7, no 7, article id e39512
National Category
Cell and Molecular Biology Endocrinology and Diabetes
Identifiers
URN: urn:nbn:se:oru:diva-63668DOI: 10.1371/journal.pone.0039512ISI: 000306436300008PubMedID: 22792179Scopus ID: 2-s2.0-84863613745OAI: oai:DiVA.org:oru-63668DiVA, id: diva2:1169231
Note

Funding agencies:

Diabetes UK  

EU HEPADIP FP6 (Hepatic and Adipose Tissue and Functions in the Metabolic Syndrome)  

The Medical Research Council Centre for Obesity Related Disorders  

Medical Research Council  

Available from: 2017-12-22 Created: 2017-12-22 Last updated: 2018-01-23Bibliographically approved

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Oresic, Matej

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