Salivary Glands treated with AAV vectors encoding PYY and exendin-4 impact upon taste perception and body mass accumulation in mice

Abstract

ABSTRACTThe availability of high-calorie foods is likely a causative factor for high rates of obesity and metabolic disorders, which have been linked to food intake dysregulation. Several gut peptides have been implicated in feeding modulation and body mass accumulation. For example, glucagon peptide-like 1 (GLP-1) and peptide tyrosinetyrosine (PYY) have been shown to mediate satiety and reduce food intake. While systemic administration of such peptides has been explored as a therapy for metabolic disease, the effects of these hormones on taste signaling should also be considered given the importance of taste to feeding decisions. Peptide signaling systems are present in taste buds and oral GLP-1 and PYY signaling has been shown to influence taste responsiveness and feeding. Indeed, we previously demonstrated that genetic knockout of PYY in mice can impact on taste responsiveness and feeding and that viral overexpression of PYY in the salivary glands of these mice can rescue responsiveness. The present work uses AAV-mediated salivary gland treatment of both GLP-1 receptor agonist exendin-4 and PYY encoding vectors to explore the impact of the presence of these peptides on taste and body-mass accumulation in wild-type mice with intact peptide signaling systems. Results showed a significant effect of salivary gland treatment on responsiveness to multiple taste qualities. Treatment with a vector designed to overexpress both peptides in saliva resulted in substantial reduction in body mass accumulation. These findings show taste modulation and impacts on body mass accumulation by the targeting of salivary glands with vectors designed to overexpress metabolic peptides in wild-type mice and suggest that the taste bud is a promising substrate for food intake modulation.