title: A new role for lipocalin prostaglandin d synthase in the regulation of brown adipose tissue substrate utilization.
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.
authors.affiliation: University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke’s Treatment Centre, Addenbrooke’s Hospital, Cambridge, U.K. sv234@medschl.cam.ac.uk
authors.forename: Sam
authors.initials: S
authors.lastname: Virtue
authors.forename: Helena
authors.initials: H
authors.lastname: Feldmann
authors.forename: Mark
authors.initials: M
authors.lastname: Christian
authors.forename: Chong Yew
authors.initials: CY
authors.lastname: Tan
authors.forename: Mojgan
authors.initials: M
authors.lastname: Masoodi
authors.forename: Martin
authors.initials: M
authors.lastname: Dale
authors.forename: Chris
authors.initials: C
authors.lastname: Lelliott
authors.forename: Keith
authors.initials: K
authors.lastname: Burling
authors.forename: Mark
authors.initials: M
authors.lastname: Campbell
authors.forename: Naomi
authors.initials: N
authors.lastname: Eguchi
authors.forename: Peter
authors.initials: P
authors.lastname: Voshol
authors.forename: Jaswinder K
authors.initials: JK
authors.lastname: Sethi
authors.forename: Malcolm
authors.initials: M
authors.lastname: Parker
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Urade
authors.forename: Julian L
authors.initials: JL
authors.lastname: Griffin
authors.forename: Barbara
authors.initials: B
authors.lastname: Cannon
authors.forename: Antonio
authors.initials: A
authors.lastname: Vidal-Puig
mesh_terms: D002001:Adipose Tissue, Brown / Q000378:metabolism*; D000818:Animals; D001823:Body Composition / Q000235:genetics / Q000502:physiology; D002460:Cell Line; D005260:Female; D019746:Intramolecular Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D054834:Lipocalins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D060888:Real-Time Polymerase Chain Reaction; D022722:Thermogenesis / Q000235:genetics / Q000502:physiology; D014280:Triglycerides / Q000378:metabolism
chemical_list: D054834:Lipocalins; D014280:Triglycerides; D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase