Potential Roles of Phosphodiesterase 3B Knockout in Acquisition of Brown Fat Characteristics by White Adipose Tissue in Mice

The cyclic nucleotide phosphodiesterase 3B (PDE3B) regulates energy metabolism. PDE3B knockout (KO) mice in SvJ129 background have less white adipose tissue (WAT) than their wild type (WT) counterparts. Furthermore, their white fat shows characteristics of brown adipose tissue (BAT) and is geared towards burning excessive energy. This phenotype is less pronounced in PDE3B KO mice in C57/BL6 background, which are prone to obesity. We have studied genetic and protein profiles of both PDE3B KO strains to dissect genes involved in WAT transdifferentiation. Thus, certain BAT-genes, e.g. PPARα and PRDM16, were up-regulated in KO as compared to WT in both strains. However, increased expression of BAT-related UCP1 and decreased expression of WAT-related p107 and RIP 140 were seen only in SvJ129 PDE3B KO. C57/BL6 mice were treated with the β3-adrenergic agonist, CL316243, resulting in reduced expression of genes related to de novo adipogenesis (RIP140, p107, PRDM16, CtBP) and increased expression of genes associated with WAT to BAT transdifferentiation (C/EBPβ, cyclooxygenase-2). Proteins involved in fatty acid oxidation and thermogenesis (PGC1α, PPARδ, UCP1) were increased upon CL316243 treatment of C57/BL6 PDE3B KO mice. Also, oxygen consumption after treatment with β3-adrenergic agonist was higher in PDE3B KO mice as compared to their WT counterparts.