Amid much controversy, the Drosophila Department of Agriculture recently published a new food pyramid and updated the serving size recommendations for various fruits. Members of the fly community across the nation are now struggling to adjust their diets, hoping these new regulations will result in healthier body weights, longer lifespan, and increased reproductive success.
We live in a society in which the words “nutritious” and “healthy” are informed by decades upon decades of scientific research on what food components help us stay energized, keep our bones strong, boost our immune systems, lower cholesterol, protect against cancer, etc. Subject to innovations in research tools and data collection, these perceptions of nutrition have morphed over time. (For example, a diet based on Wonder Bread today seems entirely comical, but apparently it was once in vogue.)
Other organisms, however, in the absence of a Department of Agriculture, World Health Organization, or other such institutions, must rely on internal, biological systems for determining what foods will keep them alive and healthy (I know, mind blown). Studying the mechanisms of nutrition perception in model organisms may lead to a more complete understanding of the interactions between human metabolic processes and brain systems, many of which remain unknown.
This week’s seminar speaker, Dr. Hubert Amrein from Texas A&M, studies taste and internal nutrient perception in Drosophila. He recently published a study (Miyamoto et al. 2012) throwing a spotlight on a certain taste receptor also endowed with fantastic nutrition-sensing ability. The star of the show is Gr43a, a member of the gustatory receptor (GR) family. GRs are present on gustatory receptor neurons (GRNs), located in taste sensillae (basically Drosophila taste buds) on various external body parts such as the proboscis and legs.
Gr43a caught the interest of Dr. Amrein and his lab because it is one of few Gr genes to have orthologs across insect species; this conservation suggests that Gr43a might play a more important role than its evolutionarily dispensable Gr counterparts. Dr. Amrein and his team established that Gr43a is a specific, high-affinity fructose receptor present not only in the sensory neurons but also in the brain. But the fly discovered that the food was sweet the moment he extended his little proboscis towards it, so what is the purpose of having a gustatory receptor in the CNS??
As neuroscientists, we spend a lot of time thinking about neurons and synapses, how we create memories, move muscles, and observe our environment. Many of us tend to forget about the vasculature that winds its way through the brain delivering oxygen and sugar. It turns out that the Gr43a receptors in the brain act as a sensor for fructose circulating in the hemolymph (essentially a fancy name for Drosophila blood)! The authors found that after a fly feasts on the sugarlicious fruit on your kitchen counter, the circulating levels of other sugars (namely glucose and trehalose) remain relatively constant while fructose levels, which are normally quite minimal, shoot up until they are high enough to stimulate those Gr43a receptors in the brain. In this way, Gr43a stimulation acts as an indicator of a nutritious meal.
Delving further into the idea of Gr43a as a nutrition sensor, the authors used the capillary feeding (CAFE) assay in which hungry flies had a choice between water and sorbitol, which is tasteless but nutritious. Gr43a mutant flies had no preference, but wildtype flies preferred the sorbitol (somehow—aka via their Gr43a receptors—they just knew it was providing much-needed sugary goodness). The Gr43a mutants, on the other hand, entirely nonplussed by both meal choices, showed no preference. Look at Gr43a, saving flies from their pangs of hunger. What a hero! But is he just a clutch hitter or does he also perform when flies are happily satiated and the game isn’t on the line?
The authors did a second CAFE assay with satiated flies and allowed them to choose among a array of nutritious, sweet-tasting sugars. Intriguingly, the Gr43a mutants went hog-wild and devoured 60-80% more sugar than the wildtype flies! However, when the assay was repeated with sweet, non-nutritious sugars (sugars that cannot be converted to fructose), there was no difference in feeding amount between the two groups, suggesting that in satiated flies, Gr43a acts to suppress rather than promote nutrient intake. So not only is our hero a lifesaver in sticky situations, he also endows flies with a modicum of self-control.
Could Gr43’s awesome bidirectional powers arise from an ability to change valence depending on the feeding state? To address this question, the authors created flies that had temperature sensitive TRPA1 ion channels in their Gr43a brain neurons. Effectively, if flies at ambient 23 °C were moved to above 25 °C, their TRPA1 channels opened, activating neurons expressing Gr43a. This allows control of Gr43a neurons completely independent of hemolymph fructose concentration. Flies were exposed to odor A at 29 °C (activated Gr43a-expressing neurons) and to odor B at 23 °C (inactive Gr43a neurons). Then they had to decide between A and B in a T-maze odor choice assay. Odor A was a magnet for hungry flies, but satiated flies wanted nothing to do with it (Fig. 7A-B). These results imply that, via the Gr43a receptor, fructose triggers a pleasant sensation in hungry flies and an aversive sensation in satiated flies (Fig. 7C)!
I should mention that it gets more complicated for mammals; in mice, fructose promotes feeding behavior while glucose suppresses it. So don’t go seeking all of the high fructose corn syrup you can find—it likely will not aid your food-related self-control as it does for our fly friends.
If you’re hungry for more on this fascinating topic, please come listen to Dr. Hubert Amrein’s talk this Tuesday at 4pm in the CNCB large conference room… It’s going to be sweet!
Catie Profaci is a first-year Neurosciences student currently rotating with Dr. Byungkook Lim. When she is not in lab, you likely can find her running barefoot on the beach, listening to NPR, cooking and consuming spicy food, or watching the Yankees game.
Miyamoto T., Xiangyu Song & Hubert Amrein (2012). A Fructose Receptor Functions as a Nutrient Sensor in the Drosophila Brain, Cell, 151 (5) 1113-1125. DOI: http://dx.doi.org/10.1016/j.cell.2012.10.024