Azelaic acid induces cholecystokinin secretion and reduces fat-rich food preference via activation of Olfr544

Olfactory receptor 544 (Olfr544) is expressed in extra-nasal tissues and has been shown to reduce adiposity and shift fuel preference to fats. Here, we investigated whether Olfr544 regulates feeding behavior. Azelaic acid increased cholecystokinin (CCK) secretion ex vivo and in vivo by Olfr544 dependently. In a two-food choice study, oral administration of azelaic acid reduced high fat diet (HFD) intake and increased normal diet (ND) intake, which was abolished in Olfr544-knockout mice. In a two-bottle preference test, the oral administration of azelaic acid reduced the intake of linoleic acid solution while increasing the intake of control solution (xanthan gum) and the effect of azelaic acid disappeared in Olfr544-knockout mice. Intraperitoneal injection of proglumide, a CCK-1/2 receptor antagonist, negated the effect of azelaic acid in reducing fat preference. Collectively, our findings suggested that Olfr544 activation by azelaic acid reduced calorie-rich high-fat food intake mediated, at least in part, by CCK secretion.