Role of human carbonic anhydrase isoforms VA and VB in obesity: Implications, mechanisms, and therapeutic prospects

Carbonic anhydrases (CAs, EC 4.2.1.1) are metalloenzymes ubiquitous in both prokaryotes and eukaryotes and catalyze a very basic physiological reaction. In particular, hCA VA and hCA VB isoenzymes are mitochondrial isoforms that are involved in metabolic processes such as ureagenesis, gluconeogenesis, and de novo lipogenesis by providing bicarbonate. The development of inhibitors for hCA VA and hCA VB commenced following the observation of weight loss, a metabolic adverse effect, in epileptic patients who were using antiepileptic medicines such as topiramate, zonisamide, and acetazolamide. Based on the structures of these drugs, the rational drug design technique, together with the famous “tail approach” was applied to develop novel hCA VA and hCA VB inhibitors that have potential as anti-obesity drug candidates. This review summarizes the implication of hCA VA and hCA VB in the pathophysiology of obesity and the inhibitory activities of small molecules developed against hCA VA and hCA VB as potential anti-obesity agents.