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A Role for Phosphodiesterase 3B in Acquisition of Brown Fat Characteristics by White Adipose Tissue in Male Mice.

Author:
  • Emilia Guirguis
  • Steven Hockman
  • Youn Wook Chung
  • Faiyaz Ahmad
  • Oksana Gavrilova
  • Nalini Raghavachari
  • Yanqin Yang
  • Gang Niu
  • Xiaoyuan Chen
  • Zu Xi Yu
  • Shiwei Liu
  • Eva Degerman
  • Vincent Manganiello
Publishing year: 2013
Language: English
Pages: 3152-3167
Publication/Series: Endocrinology
Volume: 154
Issue: 9
Document type: Journal article
Publisher: Endocrine Society

Abstract english

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 utilized 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 (Ctbp), bone morphogenetic protein 7 (Bmp7) and PR domain containing 16 (Prdm16), 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 expression of cyclooxygenase-2 (COX-2), which catalyzes prostaglandin synthesis and is thought to be important in formation of BAT in WAT, and of elongation of very long chain fatty acids 3 (Elovl3), which is linked to BAT recruitment upon cold exposure, causing a clear shift toward fat-burning and induction of BAT in KO EWAT. These data provide insight into mechanisms of BAT formation in mouse EWAT, suggesting that, in 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.

Keywords

  • Endocrinology and Diabetes

Other

Published
  • Insulin Signal Transduction
  • ISSN: 0013-7227
Eva Degerman
E-mail: eva.degerman [at] med.lu.se

Professor

Insulin Signal Transduction

+46 46 222 85 83

+46 70 885 83 62

BMC C1121b

66

Lund University Diabetes Centre, CRC, SUS Malmö, Entrance 72, House 91:12. SE-205 02 Malmö. Telephone: +46 40 39 10 00