Young children can eat bags of Halloween candy and feel fine the next day. However, adults who experience all sorts of agony following the same junk food binge. Have you ever wondered why this happens? Evolution and a gene called Foxo may be to blame. Working in fruit flies, scientists at the Buck Institute have identified a mechanism that helps the flies adapt to changes in diet when they're young; they've discovered that same mechanism gets misregulated as the flies age, disrupting metabolic homeostasis, or balance.
In a study appearing in Cell Reports, researchers focus on the function of the Foxo gene in the intestines of fruit flies. Foxo is widely expressed throughout the body (both in flies and in humans), particularly in muscle, the liver and pancreas - and can regulate many aspects of metabolism in response to insulin signaling. Lead author Jason Karpac, PhD, Assistant Research Professor at the Buck, says when young animals experience a change in diet, insulin signaling gets repressed, which turns on Foxo. "In normal young animals Foxo turns on and off quite easily, allowing for a seamless adjustment to changes in diet," said Karpac. "The process is evolutionarily conserved, it protects young animals and helps guarantee their survival," he said.
But Karpac says as the animals age, Foxo stops responding to insulin signaling (not a good thing for non-youngsters who crave that Halloween candy). "In the flies Foxo gets chronically turned on, which disrupts lipid metabolism. The process reflects the development of a general inflammatory condition in the aging gut."