Dietary fatty acids promote sleep through a taste-independent mechanism

Abstract

Consumption of foods that are high in fat contributes to obesity and metabolism-related disorders that are increasing in prevalence and present an enormous health burden throughout the world. Dietary lipids are comprised of triglycerides and fatty acids, and the highly palatable taste of dietary fatty acids promotes food consumption, activates reward centers in mammals, and underlies hedonic feeding. Despite a central role of dietary fats in the regulation of food intake and the etiology of metabolic diseases, little is known about how fat consumption regulates sleep. The fruit fly, Drosophila melanogaster, provides a powerful model system for the study of sleep and metabolic traits, and flies potently regulate sleep in accordance with food availability. To investigate the effects of dietary fats on sleep regulation, we have supplemented fatty acids into the diet of Drosophila and measured their effects on sleep and activity. We found that feeding flies a diet of hexanoic acid, a medium-chain fatty acid that is a by-product of yeast fermentation, promotes sleep by increasing the number of sleep episodes. This increase in sleep is dose-dependent and independent of the light-dark cues. Diets consisting of other fatty acids, including medium- and long-chain fatty acids, also increase sleep, suggesting many fatty acid types promote sleep. To assess whether dietary fatty acids regulate sleep through the taste system, we assessed sleep in flies with a mutation in the hexanoic acid receptor Ionotropic receptor 56d, which is required for fatty acid taste perception. We found that these flies also increase their sleep when fed a hexanoic acid diet, suggesting the sleep promoting effect of hexanoic acid is not dependent on sensory perception. Overall, these results define a role for fatty acids in sleep regulation, providing a foundation to investigate the molecular and neural basis for fatty acid-dependent modulation of sleep duration.