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

Sci Rep. 2017 Jan 13:7:40445. doi: 10.1038/srep40445.

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.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells
  • AMP-Activated Protein Kinases / metabolism*
  • Adipocytes / metabolism
  • Adipose Tissue, Beige / metabolism*
  • Adipose Tissue, White / metabolism*
  • Animals
  • Cyclic AMP / metabolism
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Cyclic Nucleotide Phosphodiesterases, Type 3 / deficiency*
  • Cyclic Nucleotide Phosphodiesterases, Type 3 / metabolism
  • Energy Metabolism
  • Enzyme Activation
  • Epididymis / metabolism
  • Female
  • Gene Knockdown Techniques
  • Male
  • Mice
  • Mice, Knockout
  • Mitochondria / metabolism
  • Obesity / metabolism
  • Obesity / prevention & control
  • Organelle Biogenesis
  • Phenotype
  • Signal Transduction*
  • Thermogenesis
  • Weight Gain

Substances

  • Cyclic AMP
  • Cyclic AMP-Dependent Protein Kinases
  • AMP-Activated Protein Kinases
  • Cyclic Nucleotide Phosphodiesterases, Type 3
  • Pde3b protein, mouse