A novel thermoregulatory role for PDE10A in mouse and human adipocytes.Phosphodiesterase type 10A (PDE10A) is highly enriched in striatum and is under evaluation as a drug target for several psychiatric/neurodegenerative diseases.  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.  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.
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