Researchers at Buck have discovered a mechanism that may explain why eating delicious but unhealthy food increases our desire to eat more.
People overeat and gain weight for various reasons. The fact that flavorful, high-calorie foods are often available anytime and anywhere doesn’t help. Researchers at Buck have found that certain chemicals called advanced glycation end products (AGEs) found in prepared and processed foods can increase hunger and reduce our willpower to make healthy choices when it comes to food. For the first time, the reason for testing abilities has been clarified.
“This research, conducted using tiny worms, has enormous implications for human dietary choices and our tendency to overeat on certain foods,” said lead author Pankaj of Bach University. Dr. Kapahi said. “Modern processed foods rich in AGEs are tempting to eat, but little is known about their long-term effects on our health.” This piece was recently published in the journal e-life.
Evolutionary perspective and the nature of AGE
“Humans have evolved certain mechanisms that encourage us to eat as much food as possible when food is plentiful. We store excess calories as fat, which we use to survive periods of fasting.” explained Muneeshu Muthaiyan Shanmugam, Ph.D., a postdoctoral fellow in the Kapahi lab and lead author of the study. “Natural selection has favored genes that preferentially consume flavorful foods, especially those high in sugar. But what are the mechanisms that make it difficult to say ‘no’ to them?”
AGEs are metabolic byproducts that occur when sugars combine with proteins, lipids, or parts of nucleic acids. acid. AGEs occur naturally when sugars are metabolized in cells, but they 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,” said Shanmugam. “Basically, we know that AGEs make food more appetizing and harder to resist.”
Maillard reaction and health effects
The “browning” reaction that occurs when sugars and proteins interact with heat is a favorite among chefs and is called the Maillard reaction. As a result, hundreds to thousands of attractive AGEs are formed.
But while the Maillard reaction is famous for its ability to make food taste good, the resulting chemicals can wreak all sorts of havoc in your body. These cause inflammation and oxidative damage, contributing to the development of blood vessel stiffness, high blood pressure, kidney disease, cancer, and neurological problems. The accumulation of these metabolic byproducts in several organs is probably one of the main factors in the aging of various organs and organisms as a whole, said Professor Kapahi, whose laboratory studies how nutrients affect health and disease. We are researching the impact it has.
“Once the advanced glycation products are formed, they cannot be detoxified,” says Shanmugam. Just like toasted white bread turns brown, this process cannot be reversed to make the bread white again. “Likewise, there is no way to reverse AGEs,” he added, adding that the body’s ability to remove AGEs decreases with age, another link to age-related diseases.
Relationship between research results and diet
Even the tiny bugs in the Kapahi lab were not immune to the temptation and damage of AGEs. Researchers observed that these chemicals not only caused disease and shortened lifespans, but also increased the worms’ appetite for the same substances. Researchers wanted to understand the mechanism by which AGEs promote preferential overeating.
To uncover the biochemical signaling pathways responsible for hyperphagia in normal, healthy worms, the researchers purified several well-studied AGEs, including two that increase food intake. Discovered AGEs. They further investigated one of the compounds to elucidate the signaling mechanism. They showed that a particular mutation (called glod-4) increases food intake through a specific AGE (called MG-H1). Further analysis revealed that a tyramine-dependent pathway was responsible.
Their work is the first to identify a signaling pathway mediated by specific AGE molecules that promotes feeding and neurodegeneration. They also found that the mutant worms, which do not have a way to process even naturally occurring AGEs, have about 25 to 30 percent shorter lifespans. The study is being extended to mice, where the researchers plan to examine the relationship between AGEs and fat metabolism.
“Understanding this signaling pathway may help us understand overeating due to modern AGE-rich diets,” Kapahi said. “Our research highlights that the accumulation of AGEs is involved in diseases such as obesity and neurodegeneration. We believe this is related to the global increase in age-related diseases.”
“Understanding this signaling pathway may help us understand overeating due to modern AGE-rich diets,” Kapahi said.
The message Shanmugam receives from his work is profound. “We don’t control our food intake; our food tries to control us,” he says.
As a result of this study and previous work in the lab, Shanmugam and Kapahi have changed the way they view their diet. They both practice intermittent fasting, which gives the body a chance to utilize fat instead of sugar. Kapahi says simple things anyone can do to reduce the burden of AGEs in the body include eating whole grains (dietary fiber helps maintain stable glucose levels) and using moist heat instead of dry cooking. This includes cooking (i.e., steaming or frying). Adding acids when cooking foods (such as grilling) slows down the reactions that lead to the formation of AGEs.
“While we are naturally attracted to delicious food, we could be more conscious of our ability to make healthy choices when we eat,” says Shanmugam.
Reference: “Methylglyoxal-derived hydroimidazolone, MG-H1, increases food intake by altering tyramine signaling through the GATA transcription factor ELT-3.” Caenorhabditis elegansMunish Muthayan Shanmugam, Jyotiska Choudhury, Durai Selegunder, Amit Kumar Sahu, Sanjiv Guha, Manish Chamoli, Brian Hodge, Neelanjan Bose, Caris Roberts, Dominic O Farella, Gordon Lithgow. , by Richmond Sarpong, James J. Galligan, and Pankaj Kapahi, September 20, 2023, e-life.
DOI: doi:10.7554/eLife.82446
Other back researchers involved in the study include Jyotiska Chaudhuri, Durai Selegounder, Amit Kumar Sahu, Sanjiv Guha, Manish Chamoli, Brian Hodge, Neelanjan Bose, and Gordon Lithgow . Other collaborators include Charis Roberts and Richmond Sarpong from the Department of Chemistry. University of California, Berkeley; Dominic O Farella 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 to reduce sugar glycation. He receives compensation in the form of equity for his role.
Acknowledgment: This research National Institutes of Health: R01AG061165, RO1AG068288, R01DK133196, and R35GM137910, and grants from the Larry L. Hillblom Foundation.