Stimulate appetite: Researchers discover why some foods make us want more

Researchers have found that AGE, a chemical in cooked food, increases hunger and affects health. AGEs are derived from the Maillard reaction and can enhance the appeal of foods but can cause health problems. Research on worms shows increased consumption and shortened lifespan due to AGEs, underscoring the importance of making healthier food choices.

Buck researchers have discovered a mechanism that explains why eating delicious but unhealthy foods makes us feel hungry.

People overeat and become overweight for many reasons. The fact that delicious, high-calorie foods are available almost everywhere doesn’t help. Buck University researchers have determined for the first time why certain chemicals in cooked or processed foods, called advanced glycation end products, or AGEs, increase hunger and test our willpower or ability to make healthy choices when it comes to food. ability.

“This study on microscopic nematodes has huge implications for humans’ dietary choices and tendency to overeat certain foods,” said Dr. Pankaj Kapahi, the Barker Professor and senior author of the study. “The processed modern diet rich in AGEs is tempting, But we know very little about its long-term effects on our health.” The work was recently published in the journal electronic life.

The evolutionary perspective and nature of AGE

“Humans have evolved mechanisms that encourage us to eat as much as possible when food is plentiful. We store excess calories as fat, which we use to survive during periods of fasting,” said Dr. Kapasi, a postdoctoral fellow in the lab and the author of the paper. explains study lead author Dr Muniesh Muthaiyan Shanmugam. “Natural selection favors genes that make us preferentially eat delicious foods, especially those with higher sugar content. But what is it about the mechanism that makes it so difficult for us to say ‘no’ to them?”

AGE is a metabolic byproduct produced when sugar combines with some proteins, lipids or nucleic acids acid. They are produced naturally when we metabolize sugar in our cells, but AGEs are also produced during baking, frying, and grilling, and are found in many processed foods. “The brown color that occurs during cooking, which makes food look and smell delicious, is a result of AGEs,” Shanmugam said. “Basically, we found that AGEs make food more palatable and more irresistible.”

Maillard reaction and health effects

The “browning” reaction that occurs when sugars and proteins interact with heat is beloved by chefs and is called the Maillard reaction. It can lead to the formation of hundreds or thousands of attractive AGEs.

However, while the Maillard reaction is famous for its ability to make food taste great, the resulting chemicals can cause all kinds of damage to the body. They cause inflammation and oxidative damage, leading to hardening of the arteries, high blood pressure, kidney disease, cancer and neurological problems. The accumulation of these metabolic byproducts in multiple organs may be one of the main drivers of aging in various organs and the entire organism, Kapahi said. Kapahi’s lab focuses on how nutrients influence health and disease.

“Once advanced glycation products are formed, they cannot be detoxified,” says Shanmugam. Like toasted white bread turning brown, the process cannot be reversed to make the bread white again. “Again, there is no way to reverse AGEs,” he said, adding that the body’s ability to clear AGEs declines with age, providing another link to age-related diseases.

Research results and dietary implications

Even the tiny worms in Kapahi’s lab can’t escape the temptation and damage caused by AGE. The researchers observed that in addition to causing disease and shortening lifespan, these chemicals increased the worms’ appetite for more of the same substance. The researchers wanted to understand the mechanisms by which AGEs stimulate preferential overeating.

To uncover the biochemical signaling pathways that cause normal, healthy worms to overeat, the researchers purified some well-studied AGEs and found that two of them increased food intake. They further explored one of the compounds to find out the signaling mechanism. They found that a specific mutation, called glod-4, increases food intake, which is mediated by a specific AGE, called MG-H1. Further analysis revealed that a tyramine-dependent pathway was responsible.

Their work is the first to identify signaling pathways mediated by specific AGE molecules that enhance feeding and neurodegeneration. They also found that mutant worms that couldn’t handle even naturally occurring AGEs had their lifespans shortened by about 25-30 percent. This work is being extended to mice, where researchers will study the connection between AGEs and fat metabolism.

“Understanding this signaling pathway may help us understand overeating as a result of modern AGEs-rich diets,” Kapahi said. “Our study highlights that AGEs accumulation is associated with disease, including obesity and neurodegenerative diseases. We believe Overall, limiting AGE accumulation is associated with a global increase in obesity and other age-related diseases.”

“Understanding this signaling pathway may help us understand overeating caused by modern AGEs-rich diets,” Kapahi said.

The message Shanmugam gained from his work was profound. “We are not controlling our food intake, but the food is trying to control us,” he said.

Because of this study and the lab’s previous research, Shanmugam and Kapahi changed the way they viewed their diet. They both practice intermittent fasting, which gives the body a chance to use fat instead of sugar. There are some simple things anyone can do to reduce the burden of AGEs in their body, Kapahi says, including eating whole grains (the fiber helps maintain stable blood sugar levels) and cooking with moist heat instead of dry heat (i.e., steaming vs. frying or grilling). ) and add acid when cooking food to slow down the reactions that lead to the formation of AGEs.

“We are naturally attracted to delicious food, but we can be more mindful of our actual ability to make healthy choices when we eat,” Shanmugam said.

Reference: “Methylglyoxal-derived hydroimidazolone MG-H1 increases food intake by altering tyramine signaling through the GATA transcription factor ELT-3 Caenorhabditis elegans” Author: Muniesh Muthaiyan Shanmugam, Jyotiska Chaudhuri, Durai Sellegounder, Amit Kumar Sahu, Sanjib Guha, Manish Chamoli, Brian Hodge, Neelanjan Bose, Charis Roberts, Dominique O Farrera, Gordon Lithgow, Richmond Saripong, James Jank, Pankr 20, 2023 Year, electronic life.
DOI: doi:10.7554/eLife.82446

Other Buck researchers involved in the study include Jyotiska Chaudhuri, Durai Sellegounder, Amit Kumar Sahu, Sanjib Guha, Manish Chamoli, Brian Hodge, Neelanjan Bose and Gordon Lithgow. Other collaborators include Charis Roberts and Richmond Sarpong of the Department of Chemistry, University of California, Berkeley; Dominique O Farrera and James Galligan, Department of Pharmacology and Toxicology, University of Arizona, Tuscany.

Disclosure/COI: Dr. Kapahi is the founder and CEO of Juvivy Health, a company developing products that reduce sugar-induced glycation. He receives compensation in the form of equity for his role.

Acknowledgments: This work was funded by: National Institutes of Health: R01AG061165, RO1AG068288, R01DK133196, and R35GM137910, and grants from the Larry L. Hillblom Foundation

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