In a new study published in eLife, researchers at Buck Institute have shed light on why some chemicals found in cooked or processed foods can lead to increased hunger and a reduced ability to make healthy dietary choices. These chemicals, known as advanced glycation end products, have been linked to overeating and obesity. This research is particularly important as it offers insights into the factors contributing to the global obesity epidemic and could help inform strategies for healthier eating habits.
Advanced glycation end products, often referred to as AGEs, are a group of complex compounds formed when sugars (carbohydrates) chemically react with proteins, lipids (fats), or nucleic acids (like DNA) in a process known as glycation. This reaction typically occurs slowly within our bodies as a natural part of aging and metabolism.
However, AGEs can also be formed much more rapidly when food is cooked or processed at high temperatures, such as when grilling, frying, or baking. This more advanced stage of glycation is known as the Maillard reaction, which is responsible for the browning and development of desirable flavors in cooked and processed foods.
AGEs are responsible for the appealing color, taste, and aroma of cooked or processed foods. Think about the crispy crust on bread, the sear on a steak, or the golden-brown color of baked goods – all of these are due, in part, to AGE formation.
“This research, done in tiny nematode worms, has immense implications for human dietary choices and the propensity to overeat certain foods,” said Pankaj Kapahi, the senior author of the study and founder of Juvify Health. “Processed modern diets enriched with AGEs are tempting to eat but we know very little about their long-term consequences on our health.”
“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, 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?”
To investigate the impact of AGEs on feeding behavior and its potential link to obesity, the researchers conducted experiments using the nematode worm, Caenorhabditis elegans, as a model organism. These tiny worms, despite their simplicity, share important biological pathways with humans, making them a valuable research tool.
The study involved analyzing the behavior of C. elegans when exposed to AGEs, specifically one type of AGE called MG-H1. The researchers found that both genetically engineered worms lacking a system to detoxify AGEs and worms exposed to MG-H1 exhibited increased feeding behavior. This suggests that the accumulation of AGEs, either due to genetic factors or dietary intake, can lead to overeating.
Kapahi told PsyPost he was surprised by “the fact that the AGE is sufficient to increase food consumption – which explains why we cook our food so much.”
Additionally, worms lacking the glyoxalase system, which detoxifies compounds like MG-H1, had significantly shorter lifespans. This highlights the potential long-term consequences of AGEs on health, even in small organisms like C. elegans.
The researchers delved deeper to understand the mechanism behind this increased feeding behavior. They identified a specific signaling pathway involving the elt-3 GATA transcription factor, which regulates the expression of the tdc-1 gene (tyramine decarboxylase) and tyramine receptors (tyra-2 and ser-2). This pathway is responsible for mediating the adverse effects of AGEs, such as increased feeding, reduced lifespan, and neuronal damage.
Importantly, this study is the first to identify this specific signaling pathway mediated by MG-H1, an AGE, and its impact on feeding and neurodegeneration. These findings highlight the harmful effects of AGEs and their contribution to diseases like obesity and neurodegeneration.
“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.”
This research helps us understand why certain foods can be hard to resist, leading to overeating and weight gain. It also highlights the harmful effects of AGEs in our diet, not only on our weight but also on our health, including our brain.
The findings indicate that “that glycation due to sugar is a major culprit behind the detrimental effects of sugar,” Kapahi told PsyPost. “It also means one should boil and stem food rather than cook on dry heat which creates AGEs. Everytime you make toast, 50+ new AGEs are generated.”
While this study provides valuable insights into how AGEs can influence feeding behavior and health, it’s important to note that C. elegans is a simple organism, and findings in these worms may not directly translate to humans.
“We need to measure more carefully that this is relevant in humans,” Kapahi said. “However, several studies support that indirectly as reducing food with AGEs is better for health.”
As AGEs are associated with various age-related diseases, including obesity and neurodegeneration, limiting their accumulation may have significant relevance for improving public health. The study’s findings suggest that mindful dietary choices, such as cooking methods and food selection, can help reduce the impact of AGEs on our health and well-being.
“My lab has also generated a supplement we call GLYLO which reduces the formation of AGEs. We find that this supplement can help slow aging and improve glucose metabolism in mice.”
The study, “Methylglyoxal-derived hydroimidazolone, MG-H1, increases food intake by altering tyramine signaling via the GATA transcription factor ELT-3 in Caenorhabditis elegans“, was published by Muniesh Muthaiyan Shanmugam, Jyotiska Chaudhuri, Durai SellegounderAmit Kumar Sahu, Sanjib Guha, Manish Chamoli, Brian Hodge, Neelanjan Bose, Charis Roberts, Dominique O. Farrera, Gordon Lithgow, Richmond Sarpong, James J Galligan, and Pankaj Kapahi.