Abstract

   Diets rich in sugar, salt, and fat alter taste perception and food
   preference, contributing to obesity and metabolic disorders, but the
   molecular mechanisms through which this occurs are unknown. Here, we
   show that in response to a high sugar diet, the epigenetic regulator
   Polycomb Repressive Complex 2.1 (PRC2.1) persistently reprograms the
   sensory neurons of Drosophila melanogaster flies to reduce sweet
   sensation and promote obesity. In animals fed high sugar, the binding
   of PRC2.1 to the chromatin of the sweet gustatory neurons is
   redistributed to repress a developmental transcriptional network that
   modulates the responsiveness of these cells to sweet stimuli, reducing
   sweet sensation. Half of these transcriptional changes persist despite
   returning the animals to a control diet, causing a permanent decrease
   in sweet taste. Our results uncover a new epigenetic mechanism that, in
   response to the dietary environment, regulates neural plasticity and
   feeding behavior to promote obesity.

INTRODUCTION

   Diets high in processed foods promote higher calorie intake and weight
   gain, increasing the risk for chronic and metabolic diseases ([34]1).
   How these foods cause overconsumption, however, is still unclear.
   Processed foods are high in salt and fat, which we are genetically
   programmed to like because of their high caloric density ([35]2).
   Evidence is emerging that the levels of salt, sugar, and fat in diets
   can alter taste sensation in humans ([36]3–[37]5), raising the question
   of whether these sensory changes may influence food intake, obesity,
   and metabolic disease ([38]6, [39]7). This idea is supported by a
   number of recent animal studies that found changes in taste, neural
   responses, and food preferences in rodents fed high-nutrient diets