White to beige conversion in PDE3B KO adipose tissue through activation of AMPK signaling and mitochondrial function

Research output: Contribution to journalArticle

Abstract

Understanding mechanisms by which a population of beige adipocytes is increased in white adipose tissue (WAT) reflects a potential strategy in the fight against obesity and diabetes. Cyclic adenosine monophosphate (cAMP) is very important in the development of the beige phenotype and activation of its thermogenic program. To study effects of cyclic nucleotides on energy homeostatic mechanisms, mice were generated by targeted inactivation of cyclic nucleotide phosphodiesterase 3b (Pde3b) gene, which encodes PDE3B, an enzyme that catalyzes hydrolysis of cAMP and cGMP and is highly expressed in tissues that regulate energy homeostasis, including adipose tissue, liver, and pancreas. In epididymal white adipose tissue (eWAT) of PDE3B KO mice on a SvJ129 background, cAMP/protein kinase A (PKA) and AMP-activated protein kinase (AMPK) signaling pathways are activated, resulting in "browning" phenotype, with a smaller increases in body weight under high-fat diet, smaller fat deposits, increased β-oxidation of fatty acids (FAO) and oxygen consumption. Results reported here suggest that PDE3B and/or its downstream signaling partners might be important regulators of energy metabolism in adipose tissue, and potential therapeutic targets for treating obesity, diabetes and their associated metabolic disorders.

Details

Authors
  • Youn Wook Chung
  • Faiyaz Ahmad
  • Yan Tang
  • Steven C. Hockman
  • Hyun Jung Kee
  • Karin Berger
  • Emilia Guirguis
  • Young Hun Choi
  • Dan M. Schimel
  • Angel M. Aponte
  • Sunhee Park
  • Eva Degerman
  • Vincent C Manganiello
Organisations
External organisations
  • National Heart Lung and Blood Institute
  • Functional Magnetic Resonance Imaging Core Facility
  • Yonsei University
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Endocrinology and Diabetes
Original languageEnglish
Article number40445
JournalScientific Reports
Volume7
StatePublished - 2017 Jan 13
Peer-reviewedYes