High Dietary Sugar Reshapes Sweet Taste to Promote Feeding Behavior in Drosophila melanogaster

Abstract

SUMMARY Recent studies find that sugar tastes less intense to humans with obesity, but whether this sensory change is a cause or a consequence of obesity is unclear. To tackle this question, we study the effects of a high sugar diet on sweet taste sensation and feeding behavior in Drosophila melanogaster. On this diet, fruit flies have lower taste responses to sweet stimuli, overconsume food, and develop obesity. Excess dietary sugar, but not obesity or dietary sweetness alone, caused taste deficits and overeating via the cell-autonomous action of the sugar sensor O-linked N-Acetylglucosamine (O-GlcNAc) transferase (OGT) in the sweet-sensing neurons. Correcting taste deficits by manipulating the excitability of the sweet gustatory neurons or the levels of OGT protected animals from diet-induced obesity. Our work demonstrates that the reshaping of sweet taste sensation by excess dietary sugar drives obesity and highlights the role of glucose metabolism in neural activity and behavior.

Persistent Epigenetic Reprogramming of Sweet Taste by Diet

“…Drosophila melanogaster fruit flies fed high dietary sugar experience lower sweet taste sensation as a result of the decreased responsiveness of the sweet sensory neurons to sugar stimuli (May et al, 2019a) . Given the importance of sensory cues to control eating, and recent data that diet also impacts taste in mammals (Ahart et al, 2019;Chen et al, 2010;Kaufman et al, 2018;Maliphol et al, 2013;May et al, 2019a;McCluskey et al, 2020;Weiss et al, 2019) , we set out to identify the molecular mechanisms through which the food environment shapes sensory responses. Since sweet taste deficits develop within 2-3 days upon exposure to the high sugar diet and independently of weight gain (May et al, 2019a) , we reasoned that gene regulatory mechanisms may be involved in modulating the responses of the sensory neurons.…”

“…Flies on a high sugar diet have lower sweet taste because the neural responses of the taste neurons to sweet stimuli are decreased (May et al, 2019a) . Since Pcl mutants have identical taste on a control and sugar diet, we hypothesized that the responses of the sensory neurons to sucrose stimulation should also be similar.…”

“…The genome shapes the sensory apparatus of each species to match their unique ecological niche, but despite this genetic constraint, this system is plastic and can be altered by diet composition (Beauchamp and Jiang, 2015) . Indeed, diet has been shown to change the taste perceptions of animals from insects to humans (Bertino et al, 1982;Glendinning et al, 2001;May et al, 2019a;Stewart and Keast, 2012;Wang et al, 2016;Wise et al, 2016;Zhang et al, 2013) , and across organisms, sensory alterations affect food preference and intake, influencing the development of conditions like obesity and heart disease (Bertino et al, 1982;May et al, 2019a;Stewart and Keast, 2012) . We recently found that high dietary sugar dulls the responses of the fruit fly taste neurons to sweet stimuli, causing higher food intake and weight gain (May et al, 2019a(May et al, , 2019b .…”

“…Indeed, diet has been shown to change the taste perceptions of animals from insects to humans (Bertino et al, 1982;Glendinning et al, 2001;May et al, 2019a;Stewart and Keast, 2012;Wang et al, 2016;Wise et al, 2016;Zhang et al, 2013) , and across organisms, sensory alterations affect food preference and intake, influencing the development of conditions like obesity and heart disease (Bertino et al, 1982;May et al, 2019a;Stewart and Keast, 2012) . We recently found that high dietary sugar dulls the responses of the fruit fly taste neurons to sweet stimuli, causing higher food intake and weight gain (May et al, 2019a(May et al, , 2019b . Mammals fed high nutrient diets also show changes in taste, neural responses, and food preferences (Ahart et al, 2019;Chen et al, 2010;Crow, 2012;Kaufman et al, 2018;Maliphol et al, 2013;May et al, 2019a;McCluskey et al, 2020;Sartor et al, 2011;Weiss et al, 2019) , arguing that the effects of diet on taste are conserved and promote obesity.…”

“…We recently found that high dietary sugar dulls the responses of the fruit fly taste neurons to sweet stimuli, causing higher food intake and weight gain (May et al, 2019a(May et al, , 2019b . Mammals fed high nutrient diets also show changes in taste, neural responses, and food preferences (Ahart et al, 2019;Chen et al, 2010;Crow, 2012;Kaufman et al, 2018;Maliphol et al, 2013;May et al, 2019a;McCluskey et al, 2020;Sartor et al, 2011;Weiss et al, 2019) , arguing that the effects of diet on taste are conserved and promote obesity. However, the molecular mechanisms through which the food environment alters taste sensation, and more broadly, neural physiology, are largely unknown.…”