Genes and brain centers that regulate meal size in flies identified

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Washington, May 21 (ANI): Scientists from the California Institute of Technology (Caltech) and Yale University have identified two genes that appear to regulate meal sizes and frequency in fruit flies.

Both genes, the leucokinin neuropeptide and the leucokinin receptor, have mammalian counterparts that seem to play a similar role in food intake, indicating that the steps that control meal size and meal frequency are not just behaviorally similar but are controlled by the same genes throughout the animal kingdom.

In animals, food intake is regulated to keep body weight constant over a long period of time. Most animals consume food in discrete bouts-that is, in meals.

"Identifying the genes and molecules that regulate meal-related parameters is essential for understanding the relationships between body weight and caloric intake," says Bader Al-Anzi, a research scientist at Caltech and the lead author of the Current Biology study.

Al-Anzi and his colleagues developed an assay to examine feeding behavior in the common fruit fly, Drosophila melanogaster. In this assay, genetically normal flies were starved for one day and then transferred into a vial containing sugar meal mixed with red food dye. Invariably, the flies became satiated during their exposure to red food, and their small abdomens turned red. Next, the researchers performed the same experiment using mutant fly strains.

"Our hope was that if flies contained mutations in genes involved in meal regulation, those flies would eat excessive amounts of red food, making them visibly bloated with red abdomens," says Al-Anzi,

Two mutant fly strains produced notable results. One strain contained a mutation in the gene encoding the leucokinin neuropeptide (a peptide initially identified for its ability to induce insect gut contraction), and the second strain contained mutated versions of the receptor that binds to leucokinin. In the assay, both types of fly mutants ate to such excess that they became visibly bloated, with their crops-food storage organs-stretched to the limit with red-dyed food.

Surprisingly, Al-Anzi says, "although in the short term these flies tend to overeat, in the long run they consume a similar amount of food as normal flies. This was largely due to the fact that they are compensating for the large increase in meal size by reducing the number of times they eat." Whereas mutant flies consumed four or five large meals in a single day, normal flies ate seven or eight small meals.

In additional experiments, Al-Anzi and his colleagues found that although the leucokinin neuropeptide is found exclusively in the brain, the leucokinin receptor is found in neurons located in both the brain and the foregut-an area of the gut that contains stretch receptors known to be responsible for monitoring meal size in other insects.

The researchers also found that introducing a normal copy of the leucokinin neuropeptide or of the leucokinin receptor gene to these neurons in their corresponding mutant flies fully restored normal feeding behavior.

Furthermore, when these same neurons were destroyed in normal, nonmutant flies, the flies began to consume abnormally large meals, just like mutants.

"This proves that we identified the right genes responsible for the flies' bingeing as well as the fly brain center that regulates meal size and frequency," Al-Anzi says.

The study will appear in the June 8 issue of the journal Current Biology. (ANI)

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