Dysregulation of hepatic cAMP levels via altered Pde4b expression plays a critical role in alcohol‐induced steatosis

• DOI: 10.1002/path.4760
• Publication Date: 2016-06-11T07:34:10Z
• Authors: Diana V Avila; David F Barker; JingWen Zhang; Craig J McClain; Shirish Barve; Leila Gobejishvili
• Keywords: Steatosis; Rolipram; Alcoholic fatty liver; Cyclic adenosine monophosphate

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 homeostasis in alcohol‐mediated never studied. Our previous work demonstrated that increased expression phosphodiesterase 4 (Pde4), which specifically hydrolyses and decreases levels, plays pathogenic development inflammation/injury. The aim this study was examine PDE4 alcohol‐induced steatosis. C57BL /6 wild‐type Pde4b knockout −/− mice were pair‐fed control or ethanol liquid diets. One group received rolipram, ‐specific inhibitor, during alcohol feeding. We demonstrate first time an early increase enzyme resultant decrease levels are associated with reduction carnitine palmitoyltransferase 1A (Cpt1a) expression. Notably, alcohol‐fed AF treated rolipram had lower free fatty acid content compared mice. Importantly, inhibition prevented Cpt1a via Pparα/Sirt1/Pgc1α pathway. These results alcohol‐ induced Pde4, expression, compromised predispose impaired oxidation Moreover, these data also suggest may be clinically relevant therapeutic target treatment Copyright © 2016 Pathological Society Great Britain Ireland. Published by John Wiley & Sons, Ltd.