The Science Behind Overeating

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In today’s world, overeating and its consequences are a growing concern. People often struggle to resist the allure of delicious, high-calorie foods that seem to be available everywhere. Recent research by Buck researchers sheds light on why certain chemicals in cooked and processed foods, known as advanced glycation end products (AGEs), can increase our hunger and challenge our willpower when it comes to making healthy food choices.

The study, conducted on tiny nematode worms, has significant implications for human dietary choices and the struggle to resist processed modern diets rich in AGEs. These diets may be tempting, but their long-term health consequences are still not well understood, according to Buck professor Pankaj Kapahi, PhD, the senior author of the study, which is published in eLife.

Our evolutionary history has wired us to seek out and consume flavorful food, especially those with higher sugar content, as a survival strategy. This preference for calorie-dense foods helped our ancestors store excess calories as fat, which they could then use during times of scarcity. However, the challenge lies in understanding the mechanisms that make it difficult to say “no” to such foods.

AGEs are metabolic by-products that naturally form when sugar combines with proteins, lipids, or nucleic acids within our bodies. They also occur during baking, frying, grilling, and are found in many processed foods. These AGEs contribute to the enticing appearance and aroma of cooked foods, making them harder to resist.

While the Maillard reaction, responsible for the “browning” of food during cooking, enhances the taste of food, it also leads to the formation of numerous AGEs. However, these chemicals wreak havoc in our bodies, causing inflammation and oxidative damage, and are associated with various health issues, including blood vessel stiffening, hypertension, kidney disease, cancer, and neurological problems.

One alarming aspect of AGEs is that once they form, they cannot be detoxified or reversed. As we age, our body’s ability to clear AGEs declines, linking them to age-related diseases.

Even the tiny worms in the Kapahi lab could not escape the allure and damage caused by AGEs. These chemicals not only contribute to disease and decreased lifespan but also increase the worms’ appetite for more of the same. The researchers aimed to uncover the biochemical signaling pathway responsible for this overeating behavior.

By isolating specific AGEs, the researchers identified two that increased food intake. Further investigation revealed a particular mutation and a tyramine-dependent pathway responsible for this effect. The study is the first to pinpoint the signaling pathway mediated by specific AGE molecules that enhance overeating and neurodegeneration.

The research has also shown that mutant worms unable to process naturally occurring AGEs have significantly shorter lifespans. This work is being extended to mice to explore the connection between AGEs and fat metabolism.

Understanding this signaling pathway may help us comprehend overeating in the context of modern diets rich in AGEs. Limiting AGEs accumulation is vital in addressing the global rise in obesity and age-related diseases, according to Kapahi.

As Muniesh Muthaiyan Shanmugam, PhD, the lead author of the study, aptly puts it, “We are not controlling our food intake, instead it is the food that is attempting to control us.” In light of this research, both Shanmugam and Kapahi have changed their dietary habits and adopted intermittent fasting, a practice that allows the body to use fat instead of sugars for energy.

There are simple steps anyone can take to reduce AGEs in their diet, including opting for whole grains, using wet heat cooking methods, and adding acids to foods during cooking to slow down the formation of AGEs. It’s a reminder that, while we are naturally drawn to delicious food, we have the power to make healthy choices when it comes to what we eat.