Potential Role of PDE3B in Acquisition of Brown Fat Characteristic by White Adipose Tissue in Mice

Abstract

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). This phenotype is less pronounced in PDE3B KO mice in C57/BL6 background, which is prone to obesity. We have studied genetic and protein profiles of both KO strains to dissect genes involved in WAT transdifferentiation. Thus, certain BAT‐genes, e.g. peroxisome proliferator‐activated receptor (PPAR) á and PRDM16 were up‐regulated in KO as compared to WT in both strains. However, increased expression of BAT‐related uncoupling protein (UCP) 1 and PPARã coactivator (PGC) 1á, as well as decreased expression of WAT‐related p107 and receptor interacting protein (RIP) 140, were seen only in SvJ129 PDE3B KO. After treatment of C57/BL6 mice with the â3‐adrenergic agonist, CL316243, expression of WAT differentiation program genes, e.g. RIP140 and p107, was reduced. In response to CL316243, some BAT‐genes were up‐regulated (CCAAT‐enhancer‐binding protein â, cyclooxygenase‐2); others, down‐regulated (PRDM16, C‐terminal binding protein). Importantly, proteins related to fatty acid oxidation and thermogenesis (PGC1á, PPARä, UCP1) were increased after treatment of C57/BL6 PDE3B KO mice with CL316243.