ArticleThe Journal of pathology2016
Dysregulation of hepatic cAMP levels via altered Pde4b expression plays a critical role in alcohol-induced steatosis.
Article in The Journal of pathology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 50 citations in OpenAlex.
- ALDH2 regulates oxaliplatin sensitivity via PDE4B in p53-mutant colorectal cancer.International journal of medical sciences · 2026Article
- Lipid Droplet Dynamics in Alcoholic Steatohepatitis.The American journal of pathology · 2026Review
- Pharmacokinetics and Biodistribution of Polymeric Nanoparticles Loaded with a Small Molecule Drug in Mice with Alcoholic Liver Disease.Molecular pharmaceutics · 2025Article
- ATP8B1 Deficiency Causes Phosphodiesterase 4-Mediated Glucagon Resistance and Impaired Gluconeogenesis in Mouse and Human Liver.Liver international : official journal of the International Association for the Study of the Liver · 2025Article
- Targeting Phosphodiesterase 4 in Gastrointestinal and Liver Diseases: From Isoform-Specific Mechanisms to Precision Therapeutics.Biomedicines · 2025Review
- Repurposing of Antiplatelet Agent: Cilostazol for the Treatment of Alcohol-Related Liver Disease.Gut and liver · 2025Review
- Cyclic nucleotide phosphodiesterases as drug targets.Pharmacological reviews · 2025Review
- The AKAP12-PKA axis regulates lipid homeostasis during alcohol-associated liver disease.Signal transduction and targeted therapy · 2025Article
- Back to phosphodiesterase inhibitors for liver disease: Are we ready for clinical trials?Hepatology (Baltimore, Md.) · 2025Article
- Dysregulated hepatic alcohol metabolism: a key factor involved in the pathogenesis of alcohol-associated liver disease.American journal of physiology. Gastrointestinal and liver physiology · 2025Article
- An Nrf2-NF-κB Crosstalk Controls Hepatocyte Proliferation in the Normal and Injured Liver.Cellular and molecular gastroenterology and hepatology · 2025Article
- Targeting cAMP signaling and phosphodiesterase 4 for liver disease treatment.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2024Article
- Ablation of secreted phosphoprotein-1 in hepatocytes increases fatty acid oxidation and ameliorates alcohol-associated liver disease.Alcohol, clinical & experimental research · 2024Article
- Article
- Hepatocyte-specific mitogen-activated protein kinase phosphatase 1 in sexual dimorphism and susceptibility to alcohol induced liver injury.Frontiers in immunology · 2024Article
- Increased expression of phosphodiesterase 4 in activated hepatic stellate cells promotes cytoskeleton remodeling and cell migration.The Journal of pathology · 2023Article
- Dysregulated Cyclic Nucleotide Metabolism in Alcohol-Associated Steatohepatitis: Implications for Novel Targeted Therapies.Biology · 2023Article
- Alcohol, White Adipose Tissue, and Brown Adipose Tissue: Mechanistic Links to Lipogenesis and Lipolysis.Nutrients · 2023Review
- The role of the tryptophan-NAD + pathway in a mouse model of severe malnutrition induced liver dysfunction.Nature communications · 2022Article
- Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Alcohol-induced hepatic steatosis is a significant risk factor for progressive liver disease. Cyclic adenosine monophosphate (cAMP) signalling has been shown to significantly regulate lipid metabolism; however, the role of altered cAMP homeostasis in alcohol-mediated hepatic steatosis has never been studied. Our previous work demonstrated that increased expression of hepatic phosphodiesterase 4 (Pde4), which specifically hydrolyses and decreases cAMP levels, plays a pathogenic role in the development of liver inflammation/injury. The aim of this study was to examine the role of PDE4 in alcohol-induced hepatic steatosis. C57BL/6 wild-type and Pde4b knockout (Pde4b(-/-) ) mice were pair-fed control or ethanol liquid diets. One group of wild-type mice received rolipram, a PDE4-specific inhibitor, during alcohol feeding. We demonstrate for the first time that an early increase in PDE4 enzyme expression and a resultant decrease in hepatic cAMP levels are associated with the significant reduction in carnitine palmitoyltransferase 1A (Cpt1a) expression. Notably, alcohol-fed (AF) Pde4b(-/-) mice and AF wild-type mice treated with rolipram had significantly lower hepatic free fatty acid content compared with AF wild-type mice. Importantly, PDE4 inhibition in alcohol-fed mice prevented the decrease in hepatic Cpt1a expression via the Pparα/Sirt1/Pgc1α pathway. These results demonstrate that the alcohol- induced increase in hepatic Pde4, specifically Pde4b expression, and compromised cAMP signalling predispose the liver to impaired fatty acid oxidation and the development of steatosis. Moreover, these data also suggest that hepatic PDE4 may be a clinically relevant therapeutic target for the treatment of alcohol-induced hepatic steatosis. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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