title: A role for phosphodiesterase 3B in acquisition of brown fat characteristics by white adipose tissue in male mice.
abstract: Obesity is linked to various diseases, including insulin resistance, diabetes, and cardiovascular disorders. The idea of inducing white adipose tissue (WAT) to assume characteristics of brown adipose tissue (BAT), and thus gearing it to fat burning instead of storage, is receiving serious consideration as potential treatment for obesity and related disorders. Phosphodiesterase 3B (PDE3B) links insulin- and cAMP-signaling networks in tissues associated with energy metabolism, including WAT. We used C57BL/6 PDE3B knockout (KO) mice to elucidate mechanisms involved in the formation of BAT in epididymal WAT (EWAT) depots. Examination of gene expression profiles in PDE3B KO EWAT revealed increased expression of several genes that block white and promote brown adipogenesis, such as C-terminal binding protein, bone morphogenetic protein 7, and PR domain containing 16, but a clear BAT-like phenotype was not completely induced. However, acute treatment of PDE3B KO mice with the β3-adrenergic agonist, CL316243, markedly increased the expression of cyclooxygenase-2, which catalyzes prostaglandin synthesis and is thought to be important in the formation of BAT in WAT and the elongation of very long-chain fatty acids 3, which is linked to BAT recruitment upon cold exposure, causing a clear shift toward fat burning and the induction of BAT in KO EWAT. These data provide insight into the mechanisms of BAT formation in mouse EWAT, suggesting that, in a C57BL/6 background, an increase in cAMP, caused by ablation of PDE3B and administration of CL316243, may promote differentiation of prostaglandin-responsive progenitor cells in the EWAT stromal vascular fraction into functional brown adipocytes.
authors.affiliation: Pulmonary Cardiovascular Branch, National Institutes of Health, Bethesda, Maryland 20892, USA. emilia.guirguis@nih.gov
authors.forename: Emilia
authors.initials: E
authors.lastname: Guirguis
authors.forename: Steven
authors.initials: S
authors.lastname: Hockman
authors.forename: Youn Wook
authors.initials: YW
authors.lastname: Chung
authors.forename: Faiyaz
authors.initials: F
authors.lastname: Ahmad
authors.forename: Oksana
authors.initials: O
authors.lastname: Gavrilova
authors.forename: Nalini
authors.initials: N
authors.lastname: Raghavachari
authors.forename: Yanqin
authors.initials: Y
authors.lastname: Yang
authors.forename: Gang
authors.initials: G
authors.lastname: Niu
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Chen
authors.forename: Zu Xi
authors.initials: ZX
authors.lastname: Yu
authors.forename: Shiwei
authors.initials: S
authors.lastname: Liu
authors.forename: Eva
authors.initials: E
authors.lastname: Degerman
authors.forename: Vincent
authors.initials: V
authors.lastname: Manganiello
mesh_terms: D050156:Adipogenesis / Q000187:drug effects; D002001:Adipose Tissue, Brown / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D052436:Adipose Tissue, White / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D058667:Adrenergic beta-3 Receptor Agonists / Q000494:pharmacology; D053687:Adult Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D003433:Crosses, Genetic; D000242:Cyclic AMP / Q000378:metabolism*; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D004149:Dioxoles / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D004822:Epididymis; D020869:Gene Expression Profiling; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D015363:Quinolones / Q000494:pharmacology
chemical_list: D058667:Adrenergic beta-3 Receptor Agonists; D015415:Biomarkers; D004149:Dioxoles; D010726:Phosphodiesterase Inhibitors; D015363:Quinolones; C076126:disodium (R,R)-5-(2-((2-(3-chlorophenyl)-2-hydroxyethyl)-amino)propyl)-1,3-benzodioxole-2,3-dicarboxylate; C021294:cilostamide; D000242:Cyclic AMP; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; C517293:Pde3b protein, mouse