Adcy3, also known as adenylate cyclase 3, is a transmembrane enzyme and a ciliary adenylyl cyclase. It localizes in primary neuronal cilia and plays a key role in regulating body weight. It is involved in pathways related to energy metabolism and neuronal signaling, and its dysfunction is associated with ciliopathies, obesity, diabetes, and epilepsy [1,2,3,4,5]. Genetic models, such as knockout (KO) mouse models, are valuable for studying its functions.

In KO mouse models, male mice lacking a cold-inducible truncated isoform of Adcy3 (Adcy3-at) display increased energy expenditure and are resistant to obesity and metabolic imbalances, suggesting that Adcy3-at acts as a rheostat in brown adipose tissue (BAT) function [6]. In rats with a protein-coding mutation in Adcy3, both heterozygous knockout (Adcy3+/-) and mutant (Adcy3mut/mut) rats have increased fat mass, with sex-dependent differences in the mechanisms (increased food intake in males, decreased energy expenditure in females), and also altered emotional behaviors [7].

In conclusion, Adcy3 is essential for regulating body weight, energy metabolism, and BAT function. Studies using KO mouse and rat models have revealed its role in obesity and related metabolic and emotional phenotypes, providing insights into the molecular mechanisms underlying these disease conditions.