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Publication : A new role for lipocalin prostaglandin d synthase in the regulation of brown adipose tissue substrate utilization.

First Author  Virtue S Year  2012
Journal  Diabetes Volume  61
Issue  12 Pages  3139-47
PubMed ID  22923471 Mgi Jnum  J:208499
Mgi Id  MGI:5563618 Doi  10.2337/db12-0015
Citation  Virtue S, et al. (2012) A new role for lipocalin prostaglandin d synthase in the regulation of brown adipose tissue substrate utilization. Diabetes 61(12):3139-47
abstractText  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 gamma coactivator 1alpha or 1beta 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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