Are We Controlling Food Intake Or Is It Controlling Us?

"This research, done in tiny nematode worms, has immense implications for human dietary choices and the propensity to overeat certain foods," said Buck professor Pankaj Kapahi, Ph.D., the senior author of the study. "Processed modern diets enriched with AGEs are tempting to eat but we know very little about their long-term consequences on our health." The work is currently published in eLife.

"Humans evolved certain mechanisms that encourage us to eat as much food as possible during times of plenty. We store the excess calories as fat that we use to survive times of fasting," explained Muniesh Muthaiyan Shanmugam, Ph.D., a postdoctoral research fellow in the Kapahi laboratory, and the lead author of the study. "Natural selection favored genes that makes us preferentially consume flavorful food, especially those with higher sugar content. But what is the mechanism that makes it so hard to say 'no' to them?"

Advanced glycation end products (AGEs) are metabolic by-products that occur when a sugar combines with part of a protein, lipid, or nucleic acid. AGEs also occur naturally when we metabolize sugars in a cell, but more to the point, they are created during baking, frying, and grilling, and AGEs are present in many processed foods. 

That lovely brown color that appears during cooking that makes food look and smell so yummy is a result of AGEs making food more appetizing and harder to resist. Browning is a reaction that occurs when sugar and protein interact with heat, and is called the Maillard reaction which is beloved among chefs and results in hundreds to thousands of mouthwateringly enticing AGEs.

While the Maillard reaction does have a claim to fame due to tantalizing delicacies, the resulting chemicals can run amok in the body wreaking havoc. AGEs cause neurological problems, inflammation, oxidative damage, hypertension, kidney disease, and certain cancers, as well as contribute to the development of blood vessel stiffening for starters. It is also believed that the accumulation of these metabolic by-products in several organs is likely to be one of the major drivers of the aging of various organs and the organism as a whole, according to the researchers. 

"Once advanced glycation products are formed, they cannot be detoxified," Shanmugam said. Just as toasted white bread becomes brown, the process can't be reversed to make the bread white again. "Similarly, there is no way to reverse the AGEs," adding that the body's ability to clear AGEs declines with age, providing another link to age-related disease.

In their studies, the researchers observed these chemicals in addition to causing disease and decreasing longevity by 25-30%, increased the appetites of worms for more of the same food. To investigate the biochemical signaling pathway for overeating in normal healthy worms some well-studied AGEs were purified, and of these 2 were found to increase eating. A mutation called glod-4 was shown to increase food intake, mediated by an AGE called MG-H1, and further analysis revealed a tyramine-dependent pathway was responsible. 

"Understanding this signaling pathway may help us to understand overeating due to modern AGEs-rich diets," said Kapahi. "Our study emphasizes that AGEs accumulation is involved in diseases, including obesity and neurodegeneration. We think that overall, limiting AGEs accumulation is relevant to the global increase in obesity and other age-associated diseases."

"We are not controlling our food intake, instead it is the food that is attempting to control us," said Shanmugam.

Both Shanmugam and Kapahi have changed the way they view their own diets, and have begun to practice intermittent fasting, which gives the body a chance to use fat instead of sugars. There are simple things that anyone can do to reduce the burden of AGEs in their bodies, said Kapah. As is including eating whole grains (the fiber helps maintain stable glucose levels), cooking with wet heat rather than dry (i.e., steaming vs. frying or grilling), and adding acid when cooking foods which slows the reaction that leads to the formation of AGEs, according to the researchers.

"We are naturally attracted to delicious food, but we could be more mindful that we do have the ability to make healthy choices when we eat," said Shanmugam.