Dietary fatty acids promote sleep through a taste-independent mechanism

Abstract

300 words 16 Introduction: 559 words Abstract 19Consumption of foods that are high in fat contributes to obesity and metabolism-related 20 disorders that are increasing in prevalence and present an enormous health burden throughout 21 the world. Dietary lipids are comprised of triglycerides and fatty acids, and the highly palatable 22 taste of dietary fatty acids promotes food consumption, activates reward centers in mammals, 23 and underlies hedonic feeding. Despite a central role of dietary fats in the regulation of food 24 intake and the etiology of metabolic diseases, little is known about how fat consumption 25 regulates sleep. The fruit fly, Drosophila melanogaster, provides a powerful model system for 26 the study of sleep and metabolic traits, and flies potently regulate sleep in accordance with food 27 availability. To investigate the effects of dietary fats on sleep regulation, we have supplemented 28 fatty acids into the diet of Drosophila and measured their effects on sleep and activity. We found 29 that feeding flies a diet of hexanoic acid, a medium-chain fatty acid that is a by-product of yeast 30 fermentation, promotes sleep by increasing the number of sleep episodes. This increase in 31 sleep is dose-dependent and independent of the light-dark cues. Diets consisting of other fatty 32acids, including medium-and long-chain fatty acids, also increase sleep, suggesting many fatty 33 acid types promote sleep. To assess whether dietary fatty acids regulate sleep through the taste 34 system, we assessed sleep in flies with a mutation in the hexanoic acid receptor Ionotropic 35 receptor 56d, which is required for fatty acid taste perception. We found that these flies also 36 increase their sleep when fed a hexanoic acid diet, suggesting the sleep promoting effect of 37 hexanoic acid is not dependent on sensory perception. Overall, these results define a role for 38 fatty acids in sleep regulation, providing a foundation to investigate the molecular and neural 39 basis for fatty acid-dependent modulation of sleep duration. 40 41