Journal
DIABETES
Volume 61, Issue 12, Pages 3139-3147Publisher
AMER DIABETES ASSOC
DOI: 10.2337/db12-0015
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Funding
- Diabetes U.K.
- EU HEPADIP FP6
- The Medical Research Council Centre for Obesity Related Disorders
- Medical Research Council
- Swedish Research Council
- ADAPT FP7
- BBSRC
- Biotechnology and Biological Sciences Research Council [BB/H013539/1, BB/H013539/2, JF16994] Funding Source: researchfish
- British Heart Foundation [PG/10/38/28359] Funding Source: researchfish
- Medical Research Council [G0802051, G0600717B, MC_UP_A090_1006] Funding Source: researchfish
- BBSRC [BB/H013539/1, BB/H013539/2] Funding Source: UKRI
- MRC [G0802051, MC_UP_A090_1006] Funding Source: UKRI
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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 1 alpha or 1 beta 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 mid 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 knock-out 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. Diabetes 61:3139-3147, 2012
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