Hedgehog-mediated gut-taste neuron axis controls sweet perception in Drosophila

Abstract

Dietary composition affects food preference in animals. High sugar intake suppresses sweet sensation from insects to humans, but the molecular basis of this suppression is largely unknown. Here, we reveal that sugar intake in Drosophila induces the gut to express and secrete Hedgehog (Hh) into the circulation. We show that the midgut secreted Hh localize to taste sensilla and suppresses sweet sensation, perception, and preference. We further find that the midgut Hh inhibits Hh signalling in the sweet taste neurons. Our electrophysiology studies demonstrate that the midgut Hh signal also suppresses bitter taste and some odour responses, affecting overall food perception and preference. We further show that the level of sugar intake during a critical window early in life, sets the adult gut Hh expression and sugar perception. Our results together reveal a bottom-up feedback mechanism involving a “gut-taste neuron axis” that regulates food sensation and preference.

Overlap and divergence of neural circuits mediating distinct behavioral responses to sugar

“…Taken together with previous studies testing proboscis extension, 17, 39 these results suggest that excess dietary sugar globally dampens short-term behavioral responses to sugar. Because we used optogenetic stimulation of sugar neurons, which bypasses sugar receptor activation, our results additionally demonstrate that a high-sugar diet decreases sugar sensitivity by acting downstream of the sugar receptors.…”

“…A high-sugar diet reduces proboscis extension to sugar but leads to increased long-term feeding. 15,17,39 We found that a high-sugar diet reduces other behavioral responses to sugar, suggesting that short-term responses to sugar are globally dampened. How and where does this suppression occur?…”

“…Observing an effect would suggest that a high-sugar diet affects sugar taste processing in the central brain, in addition to its known effects on sensory neurons. 17, 38, 39 For the 3 interneurons that strongly affected behavior (Rattle, FMIn, and Fdg), we compared the responses of flies raised on a control versus high-sugar diet. We focused on analyzing locomotion, as this behavior was the most robustly affected by interneuron activation.…”

Cardiaca adipokinetic hormone and hedgehog signaling combine to generate intracellular waves of Ca++in starvedDrosophila melanogasterfat body

“…Knockdown of Hh signaling leads to elevated levels of triglycerides in the D. melanogaster fat body (16, 17, 43), and canonical Hh signaling in the fat body activates the Ci transcription factor increasing the expression of the lipase encoding gene bmm (18). In D. melanogaster adults, Hh signaling from midgut ECs to the taste sensilla regulates sweet sensation and perception (44). In mouse activation of the Hh pathway in the adipocyte lineage suppresses high fat diet induced obesity (45) and signals through Gαi, extracellular Ca ++ , and Amp kinase to induce a Warburg-like shift in metabolism (26).…”

JAK-STAT pathway activation compromises nephrocyte function in aDrosophilahigh-fat diet model of chronic kidney disease

“…Immunostaining was performed as previously reported (Zhao et al, 2022) with minor changes. Flies were briefly rinsed in 95% ethanol and dissected in 1xPBS at room temperature.…”