Diet profoundly influences brain physiology, but how metabolic information is transmuted into neural activity and behavior changes remains elusive. Here, we show that the metabolic enzyme O-GlcNAc Transferase (OGT) moonlights on the chromatin of the D. melanogaster gustatory neurons to instruct changes in chromatin accessibility and transcription that underlie sensory adaptations to a high-sugar diet. OGT works synergistically with the Mitogen Activated Kinase/Extracellular signal Regulated Kinase (MAPK/ERK) rolled and its effector stripe (also known as EGR2 or Krox20) to integrate activity information. OGT also cooperates with the epigenetic silencer Polycomb Repressive Complex 2.1 (PRC2.1) to decrease chromatin accessibility and repress transcription in the high-sugar diet. This integration of nutritional and activity information changes the taste neurons’ responses to sugar and the flies’ ability to sense sweetness. Our findings reveal how nutrigenomic signaling generates neural activity and behavior in response to dietary changes in the sensory neurons.
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Persistent epigenetic reprogramming of sweet taste by diet
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.
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- Award ID(s):
- 1941822
- NSF-PAR ID:
- 10274801
- Date Published:
- Journal Name:
- Science Advances
- Volume:
- 6
- Issue:
- 46
- ISSN:
- 2375-2548
- Page Range / eLocation ID:
- eabc8492
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Objective Previous studies have reported that individuals with obesity have reduced taste perception, but the relationship between obesity and taste is poorly understood. Earlier work has demonstrated that diet‐induced obesity directly impairs taste. Currently, it is not clear whether these changes to taste are due to obesity or to the high‐fat diet exposure. The goal of the current study was to determine whether diet or excess weight is responsible for the taste deficits induced by diet‐induced obesity.
Methods C57BL/6 mice were placed on either high‐fat or standard chow in the presence or absence of captopril. Mice on captopril did not gain weight when exposed to a high‐fat diet. Changes in the responses to different taste stimuli were evaluated using live cell imaging, brief‐access licking, immunohistochemistry, and real‐time polymerase chain reaction.
Results Diet and weight gain each affected taste responses, but their effects varied by stimulus. Two key signaling proteins, α‐gustducin and phospholipase Cβ2, were significantly reduced in the mice on the high‐fat diet with and without weight gain, identifying a potential mechanism for the reduced taste responsiveness to some stimuli.
Conclusions Our data indicate that, for some stimuli, diet alone can cause taste deficits, even without the onset of obesity.
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Many mammals can digest starch by using an enzyme called amylase, but different species eat different amounts of starchy foods. Amylase is released by the pancreas, and in certain species such as humans, it is also created by the glands that produce saliva, allowing the enzyme to be present in the mouth. There, amylase can start to break down starch, releasing a sweet taste that helps the animal to detect starchy foods. Curiously, humans have multiple copies of the gene that codes for the enzyme, but the exact number varies between people. Previous research has found that populations with more copies also eat more starch; if this correlation also existed in other species, it could help to understand how diets influence and shape genetic information. In addition, it is unclear how amylase came to be present in saliva, as the ancestors of mammals only produced the protein in the pancreas. Pajic et al. analyzed the genomes of a range of mammals and found that the more starch a species had in its diet, the more amylase gene copies it harbored in its genome. In fact, unrelated mammals living in different habitats and eating different types of food have similar numbers of amylase gene copies if they have the same level of starch in their diet. In addition, Pajic et al. discovered that animals such as mice, rats, pigs and dogs, which have lived in close contact with people for thousands of years, quickly adapted to the large amount of starch present in human food. In each of these species, a mechanism called gene duplication independently created new copies of the amylase gene. This could represent the first step towards some of these copies becoming active in the glands that release saliva. In people, having fewer copies of the amylase gene could mean they have a higher risk for diabetes; this number is also tied to the composition of the collection of bacteria that live in the mouth and the gut. Understanding how the copy number of the amylase gene affects biology will help to grasp how it also affects health and wellbeing, in humans and in our four-legged companions.more » « less
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Animals inhabiting subterranean environments tend to evolve a constellation of ‘regressive’ and ‘constructive’ features. Regressive traits like vision and pigmentation are reduced or lost in derived organisms. In contrast, constructive traits like non-visual sensation, are commonly augmented and evolving under strong selection. Numerous studies have examined the genetic, developmental and molecular bases for regressive traits, while constructive traits have received less attention. A key constructive sensory feature in cave animals is the gustatory system which is likely useful for animals living in complete darkness, given the need to secure food for survival. Interestingly, despite having been studied for decades in the Mexican tetra, Astyanax mexicanus , much remains unknown regarding the biological basis, and adaptive relevance, of taste system evolution in cave morphs. Here, we present a brief review of taste system research in this system, conducted over the past ~90 years. We underscore key differences in gustation between cave and surface fish that reside at the levels of anatomy, perception and behavior. From this review, we sought to identify key knowledge gaps in our understanding of constructive taste system evolution. Future studies will provide further insights to the nature of constructive trait evolution by determining if constructive and regressive traits evolve through similar or different genetic and developmental mechanisms, and provide an essential case study for examining convergence of constructive traits across geographically distinct populations.more » « less
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Background Bitter and sweet taste receptors are present in the human upper airway, where they have roles in innate immunity. Previous studies have shown that 1 of the 25 bitter receptors,
TAS2R38 , responds to specific bacterial signaling molecules and evokes 1 type of a defense response in the upper airway, whereas ligands of sweet receptors suppress other types of defense responses.Methods We examined whether other bitter taste receptors might also be involved in innate immunity by using sensory responses to bitter compounds that are not ligands of
TAS2R38 (quinine and denatonium benzoate) to assess the sensitivity of other bitter receptors in chronic rhinosinusitis (CRS) patients. CRS patients with (n = 426) and without (n = 226) nasal polyps and controls (n = 356) rated the intensity of quinine, denatonium benzoate, phenylthiocarbamide (PTC; a ligand forTAS2R38 ), sucrose, and salt.Results CRS patients rated the bitter compounds denatonium benzoate and quinine as less intense and sucrose as more intense than did controls (false discovery rate [FDR] <0.05) and CRS patients and controls did not differ in their ratings of salt (FDR >0.05). PTC bitter taste intensity differed between patient and control groups but were less marked than those previously reported. Though differences were statistically significant, overall effect sizes were small.
Conclusion CRS patients report bitter stimuli as less intense but sweet stimuli as more intense than do control subjects. We speculate that taste responses may reflect the competence of sinonasal innate immunity mediated by taste receptor function, and thus a taste test may have potential for clinical utility in CRS patients.
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1126/sciadv.abc8492
