ArticleMolecular pharmacology2013
PDE3 and PDE4 isozyme-selective inhibitors are both required for synergistic activation of brown adipose tissue.
Article in Molecular pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 45 citations in OpenAlex.
- Review
- Adipocyte Browning: A Promising Avenue in Anti-Obesity Therapy.International journal of molecular sciences · 2026Review
- Inhibition of adipocyte lipolysis by vaspin impairs thermoregulation in vivo.Nature communications · 2025Article
- The role of compartmentalized β-AR/cAMP signaling in the regulation of lipolysis in white and brown adipocytes.The FEBS journal · 2025Review
- Inhibition of AXL receptor tyrosine kinase enhances brown adipose tissue functionality in mice.Nature communications · 2023Article
- Molecular Basic of Pharmacotherapy of Cytokine Imbalance as a Component of Intervertebral Disc Degeneration Treatment.International journal of molecular sciences · 2023Review
- Pharmacological Management of Obesity in Patients with Polycystic Ovary Syndrome.Biomedicines · 2023Article
- The Complexity and Multiplicity of the Specific cAMP Phosphodiesterase Family: PDE4, Open New Adapted Therapeutic Approaches.International journal of molecular sciences · 2022Review
- Inactivation of Type 3 Deiodinase Results in Life-long Changes in the Brown Adipose Tissue Transcriptome in the Male Mouse.Endocrinology · 2022Article
- FGF1 and insulin control lipolysis by convergent pathways.Cell metabolism · 2022Article
- Dual Activation of Phosphodiesterase 3 and 4 Regulates Basal Cardiac Pacemaker Function and Beyond.International journal of molecular sciences · 2021Review
- The Biological Effects of Forsythia Leaves Containing the Cyclic AMP Phosphodiesterase 4 Inhibitor Phillyrin.Molecules (Basel, Switzerland) · 2021Review
- Article
- An update of cyclic nucleotide phosphodiesterase as a target for cardiac diseases.Expert opinion on drug discovery · 2021Review
- Theobromine alleviates diet-induced obesity in mice via phosphodiesterase-4 inhibition.European journal of nutrition · 2020Article
- Real-time monitoring of cAMP in brown adipocytes reveals differential compartmentation of βMolecular metabolism · 2020Article
- A compendium of G-protein-coupled receptors and cyclic nucleotide regulation of adipose tissue metabolism and energy expenditure.Clinical science (London, England : 1979) · 2020Review
- A PDE1 inhibitor reduces adipogenesis in mice via regulation of lipolysis and adipogenic cell signaling.Experimental & molecular medicine · 2019Article
- Compound D159687, a phosphodiesterase 4D inhibitor, induces weight and fat mass loss in aged mice without changing lean mass, physical and cognitive function.Biochemical and biophysical research communications · 2018Article
- Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Brown adipose tissue (BAT) is a highly thermogenic organ that converts lipids and glucose into heat. Many of the metabolic and gene transcriptional hallmarks of BAT activation, namely increased lipolysis, uncoupling protein-1 (UCP1) mRNA, and glucose uptake, are regulated by the adrenergic second messenger, cAMP. Cyclic nucleotide phosphodiesterases (PDEs) catalyze the breakdown of cAMP, thereby regulating the magnitude and duration of this signaling molecule. In the absence of adrenergic stimulus, we found that it required a combination of a PDE3 and a PDE4 inhibitor to fully induce UCP1 mRNA and lipolysis in brown adipocytes, whereas neither PDE inhibitor alone had any substantial effect under basal conditions. Under submaximal β-adrenoceptor stimulation of brown adipocytes, a PDE3 inhibitor alone could potentiate induction of UCP1 mRNA, whereas a PDE4 inhibitor alone could augment lipolysis, indicating differential roles for each of these two PDEs. Neither induction of UCP1 nor lipolysis was altered by inhibition of PDE1, PDE2, or PDE8A. Finally, when injected into mice, the combination of PDE3 and PDE4 inhibitors stimulated glucose uptake in BAT under thermoneutral and fasted conditions, a response that was further potentiated by the global ablation of PDE8A. Taken together, these data reveal that multiple PDEs work in concert to regulate three of the important pathways leading to BAT activation, a finding that may provide an improved conceptual basis for the development of therapies for obesity-related diseases.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.