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

Guirguis, Emilia; Hockman, Steven; Chung, Youn Wook; Ahmad, Faiyaz; Gavrilova, Oksana; Raghavachari, Nalini; Yang, Yanqin; Niu, Gang; Chen, Xiaoyuan and Yu, Zu Xi, et al. (2013) In Endocrinology 154(9). p.3152-3167
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 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... (More)
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. (Less)
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Endocrinology
volume
154
issue
9
pages
3152 - 3167
publisher
Endocrine Society
external identifiers
  • wos:000323620100020
  • pmid:23766131
  • scopus:84883142792
ISSN
0013-7227
DOI
10.1210/en.2012-2185
language
English
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yes
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1c8995db-90c5-4b46-957a-75953f91e5c1 (old id 3913370)
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http://www.ncbi.nlm.nih.gov/pubmed/23766131?dopt=Abstract
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2013-07-01 13:29:42
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2019-02-20 03:07:37
@article{1c8995db-90c5-4b46-957a-75953f91e5c1,
  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 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.},
  author       = {Guirguis, Emilia and Hockman, Steven and Chung, Youn Wook and Ahmad, Faiyaz and Gavrilova, Oksana and Raghavachari, Nalini and Yang, Yanqin and Niu, Gang and Chen, Xiaoyuan and Yu, Zu Xi and Liu, Shiwei and Degerman, Eva and Manganiello, Vincent},
  issn         = {0013-7227},
  language     = {eng},
  number       = {9},
  pages        = {3152--3167},
  publisher    = {Endocrine Society},
  series       = {Endocrinology},
  title        = {A Role for Phosphodiesterase 3B in Acquisition of Brown Fat Characteristics by White Adipose Tissue in Male Mice.},
  url          = {http://dx.doi.org/10.1210/en.2012-2185},
  volume       = {154},
  year         = {2013},
}