Key result
PDE10A inhibitor MP-10 drives weight loss and improves insulin sensitivity in obese mice via thermogenesis.
Why the study?
Preclinical studies implicate PDE10A in the regulation of energy homeostasis, but the mechanisms remain unclear.
Does pharmacological inactivation of PDE10A with MP-10 improve thermogenesis and metabolic parameters in mouse models and human adipocytes?
Does pharmacological inactivation of PDE10A with MP-10 improve thermogenesis and metabolic parameters in mouse models and human adipocytes?
PDE10A inhibition with MP-10 promotes thermogenesis and browning of white adipose tissue, highlighting a novel therapeutic target for obesity and diabetes.
Extends PDE10A research to BAT; leaves open any human metabolic effects.
Phosphodiesterase type 10A (PDE10A) is highly enriched in striatum and is under evaluation as a drug target for several psychiatric/neurodegenerative diseases. Preclinical studies implicate PDE10A in the regulation of energy homeostasis, but the mechanisms remain unclear. By utilizing small-animal PET/MRI and the novel radioligand [(18)F]-AQ28A, we found marked levels of PDE10A in interscapular brown adipose tissue (BAT) of mice. Pharmacological inactivation of PDE10A with the highly selective inhibitor MP-10 recruited BAT and potentiated thermogenesis in vivo In diet-induced obese mice, chronic administration of MP-10 caused weight loss associated with increased energy expenditure, browning of white adipose tissue, and improved insulin sensitivity. Analysis of human PET data further revealed marked levels of PDE10A in the supraclavicular region where brown/beige adipocytes are clustered in adults. Finally, the inhibition of PDE10A with MP-10 stimulated thermogenic gene expression in human brown adipocytes and induced browning of human white adipocytes. Collectively, our findings highlight a novel thermoregulatory role for PDE10A in mouse and human adipocytes and promote PDE10A inhibitors as promising candidates for the treatment of obesity and diabetes.
No takes yet. Share an insight, caveat, or question.
Hankir et al. (2016) studied Obesity and diabetes. MP-10 (PDE10A inhibitor) was evaluated on Thermogenesis, weight loss, energy expenditure, browning of white adipose tissue, and insulin sensitivity. Pharmacological inactivation of PDE10A with MP-10 recruited brown adipose tissue, potentiated thermogenesis, and caused weight loss with improved insulin sensitivity in diet-induced obese mice.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: