scholarly journals Inhibition of phosphodiesterase type 9 reduces obesity and cardiometabolic syndrome in mice

2021 ◽  
Author(s):  
Sumita Mishra ◽  
Nandhini Sadagopan ◽  
Brittany Dunkerly-Eyring ◽  
Susana Rodriguez ◽  
Dylan C. Sarver ◽  
...  
Keyword(s):  
Cardiometabolic Syndrome ◽  
Phosphodiesterase Type

scholarly journals PDE9 Inhibition Activates PPARα to Stimulate Mitochondrial Fat Metabolism and Reduce Cardiometabolic Syndrome

2021 ◽  
Author(s):  
Sumita Mishra ◽  
Virginia S. Hahn ◽  
Nandhini Sadagopan ◽  
Brittany Dunkerly-Ering ◽  
Susana Rodriguez ◽  
...  
Keyword(s):  
Central Obesity ◽  
Fat Metabolism ◽  
Estrogen Receptor Α ◽  
Mitochondrial Activity ◽  
Preserved Ejection Fraction ◽  
Chromatin Binding ◽  
Cardiometabolic Syndrome ◽  
Diet Induced Obesity ◽  
Phosphodiesterase Type ◽  
White Fat

ABSTRACTCentral obesity with cardiometabolic syndrome (CMS) is a major global contributor to human disease, and effective therapies are needed. Here, we show inhibiting cyclic-GMP selective phosphodiesterase-9A (PDE9-I) suppresses established diet-induced obesity and CMS in ovariectomized female and male mice. PDE9-I reduces abdominal, hepatic, and myocardial fat accumulation, stimulates mitochondrial activity in brown and white fat, and improves CMS, without altering activity or food intake. PDE9 localizes to mitochondria, and its inhibition stimulates lipolysis and mitochondrial respiration coupled to PPARα-dependent gene regulation. PPARα upregulation is required for PDE9-I metabolic efficacy and is absent in non-ovariectomized females that also display no metabolic benefits from PDE9-I. The latter is compatible with estrogen receptor-α altering PPARα chromatin binding identified by ChIPSeq. In humans with heart failure and preserved ejection fraction, myocardial expression of PPARA and its regulated genes is reduced versus control. These findings support testing PDE9-I to treat obesity/CMS in men and postmenopausal women.SummaryOral inhibition of phosphodiesterase type 9 stimulates mitochondrial fat metabolism and lipolysis, reducing central obesity without changing appetite

257: The Phosphodiesterase Type 4 Inhibitor, Rolipram, is More Efficient to Relax Detrusor Smooth Muscle in Rats with Overactive Bladder than in Control Rats

2007 ◽  
Vol 177 (4S) ◽  
pp. 86-86
Author(s):  
Stephanie Oger ◽  
Delphine Behr-Roussel ◽  
Katell Mevel ◽  
Jacques Bernabe ◽  
Pierre Denys ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Overactive Bladder ◽  
Detrusor Smooth Muscle ◽  
Phosphodiesterase Type

1202: Long-Term Phosphodiesterase Type 5 Inhibitor Therapy Reduces Priapic Activity in Transgenic Sickle Cell Mice

2006 ◽  
Vol 175 (4S) ◽  
pp. 387-387 ◽  
Author(s):  
Trinity J. Bivalacqua ◽  
Hunter C. Champion ◽  
Warren Mason ◽  
Arthur L. Burnett
Keyword(s):  
Sickle Cell ◽  
Inhibitor Therapy ◽  
Phosphodiesterase Type 5 Inhibitor ◽  
Phosphodiesterase Type
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