Sumita Mishra, Nandhini Sadagopan, Brittany Dunkerly-Eyring, Susana Rodriguez, Dylan C Sarver, Ryan P Ceddia, Sean A Murphy, Hildur Knutsdottir, Vivek P Jani, Deepthi Ashok, Christian U Oeing, Brian O'Rourke, Jon A Gangoiti, Dorothy D Sears, G William Wong, Sheila Collins, David A Kass
Central obesity with cardiometabolic syndrome (CMS) is a major global contributor to human disease, and effective therapies are needed. Here, we show that cyclic GMP-selective phosphodiesterase 9A inhibition (PDE9-I) in both male and ovariectomized female mice suppresses preestablished severe diet-induced obesity/CMS with or without superimposed mild cardiac pressure load. PDE9-I reduces total body, inguinal, hepatic, and myocardial fat; stimulates mitochondrial activity in brown and white fat; and improves CMS, without significantly altering activity or food intake...
November 1, 2021: Journal of Clinical Investigation