How the fruit fly is helping researchers probe the “appetite question” behind obesity

Whether you’re watching your calories this holiday season or giving yourself a free pass to overindulge, give thanks to Drosophila melanogaster, the lowly fruit fly.

Researchers at the Texas A&M Health Science Center (TAMHSC) College of Medicine have discovered a brain-based sensor in fruit flies that could help solve the mystery of why most animals are better at regulating their food consumption than we are. Their study on the receptor, A Fructose Receptor Functions as Nutrient Sensor in the Drosophila Brain, can be read online in the scientific journal Cell and was published in the Nov. 22 print issue.

“Scientists have known that nutrient sensors play a large role in regulating how much we eat, but on a molecular level, they are poorly understood,” said Hubert Amrein, Ph.D., professor of molecular and cellular medicine in the TAMHSC-College of Medicine and leader of a research team focused on animals’ sensory perception of the external chemical world. “We studied a receptor in fruit flies that relates to eating, and the way it functions turned out to be very surprising.”According to Dr. Amrein, study senior author, whenever a fruit fly ingests a nutritious carbohydrate, there is a significant increase of fructose in its blood, activating a fructose sensor in the brain.

“We have discovered that this sensor’s activation triggers the fly to eat more or to stop eating, depending on the fly’s satiety level,” Dr. Amrein said. “In hungry flies, it promotes feeding, but in flies who are already ‘full,’ it suppresses feeding to prevent overeating.”

Dr. Amrein’s research may offer tantalizing parallels into the mammalian system – that is, in how mammals, including humans, regulate their carbohydrate intake. Converting carbohydrates into fructose and measuring the rise in fructose is more elegant than trying to assess changes in the main blood sugar, glucose, because the level of fructose in the fly’s bloodstream is very small, making increases easy to accomplish and measure.

Mice also have shown significant increase in blood fructose after a carbohydrate-rich meal. Dr. Amrein’s team, in collaboration with Raquel Sitcheran, Ph.D., assistant professor of molecular and cellular medicine in the TAMHSC-College of Medicine, is now investigating whether what Dr. Amrein calls a “surprising parallel” has direct functional consequences in how mice and possibly humans regulate carbohydrate consumption.

“The questions we see before us are large ones, and we are ultimately looking for a sugar or compound that is used as a signal that may regulate appetite and feeding activity in mammals by directly activating a nutrient sensor in the brain – the hypothalamus, for example,” Dr. Amrein said. “If we can identify a molecular sensor that operates similar to that in flies, we will better understand what drives and slows feeding behavior in humans. Given the close association of our culture’s consumption of ‘carbs’ and high-fructose soft drinks and the widening obesity epidemic in Western societies, it will be important for us to determine whether an internal fructose sensing system exists in mammals, including humans.”

Dr. Amrein discussed the study in greater depth in a recent post on the College of Medicine’s Facebook page.

Other contributors to the Cell study from the TAMHSC-College of Medicine Department of Molecular and Cellular Medicine were Tetsuya Miyamoto, Ph.D., postdoctoral research associate; Jesse Slone, now at Vanderbilt University; and Xiangyu Song, now at Proctor & Gamble Technology (Beijing). Research was supported by the National Institutes of Health.