The ketogenic (keto) diet is a low-carbohydrate, high-fat eating plan (LCHF) that is extremely popular in North America, with an estimated 5% of adults trying it in the past year alone. This diet is known for inducing a state of ketosis (where the body burns fat instead of carbohydrates for energy), which has been linked to benefits such as weight loss and improved metabolic health. However, scientists are uncovering new dimensions of how ketosis affects the body, looking beyond dietary trends to explore its profound biological effects.
Obesity remains a significant global health problem, and researchers strive to find new ways to address its underlying causes and associated challenges. A major discovery by a team of scientists led by Professor Xu Yong and Dr. Jonathan Long identified a new biochemical process, a series of chemical reactions in the body that helps sustain life, which could open the door to innovative anti-obesity treatments . The study, published in the respected journal Cell, explores how key compounds produced during fat metabolism (a metabolic state in which the body burns fat instead of carbohydrates for energy) interact with Amino acids (the building blocks of amino acids) interact with each other.
“Our study shows that the body uses ketones in other ways to contribute to energy balance by generating naturally occurring compounds during fat metabolism-derived amino acid conjugates,” explains Dr. Long of Stanford University. “These metabolites not only is merely an energy intermediate, a molecule that plays a role in storing and transferring energy within cells, and is an active regulator of physiological processes, normal functions and activities of the body. Researchers refer to this metabolic pathway as “natural in fat metabolism shunting.” compounds present”, promoted by enzymes that help process amino acids, thereby combining naturally occurring compounds with free amino acids during fat metabolism.
The most abundant product of this pathway is a compound formed from the interaction of a fat-derived molecule and an amino acid, which has shown significant effects in experimental models. In obese mice, administration of compounds formed by the interaction of fat-derived molecules and amino acids reduced food intake and promoted weight loss without adverse side effects. These findings are further supported by studies showing that genetic deletion of an enzyme in mice that helps process amino acids eliminates the production of these bioactive molecules, resulting in increased food consumption and Weight gain.
“Beta-hydroxybutyrate-phenylalanine acts on key neural pathways, neuronal networks in the brain and nervous system that transmit signals in the hypothalamus and brainstem, and the hypothalamus and brain stem,” explained researcher Xu of Baylor College of Medicine. The stem is a key region in controlling hunger and appetite, highlighting the potential for developing treatments targeting these mechanisms to control obesity.
The team’s research also confirmed that this metabolic pathway is conserved in humans. By studying blood samples, they discovered a similar naturally occurring compound involved in fat metabolism, known as amino acid compounds, that increases during ketosis caused by fasting or consuming ketone supplements. This protection emphasizes the relevance of research results and their translational potential, i.e. the possibility that scientific discoveries can be applied to practical treatments or solutions.
Summarizing the broader implications, the researchers highlight that understanding this alternative metabolic pathway could revolutionize our view of energy-related molecules formed during fat metabolism, extending their importance from mere energy substrates to being effective in metabolic health. Conditioner. Future studies aim to explore the medical use of compounds naturally occurring in metabolic processes derived from fat metabolism in the treatment of metabolic diseases, including obesity and diabetes.
As these discoveries continue to unfold, they offer a promising approach to solving one of the most pervasive health challenges of our time.
Journal reference
Moya-Garzon, MD, Wang, M., Li, VL, Xu, Y., Long, JZ, et al. “The beta-hydroxybutyrate shunt pathway produces anti-obesity ketone metabolites.” Cell, 2025.
About the author
Professor Xu Yong is a distinguished researcher specializing in molecular and cellular biology, with a special focus on metabolic regulation and energy homeostasis. Working at Baylor College of Medicine, he has made significant contributions to the understanding of the neural mechanisms that control appetite, metabolism, and weight. His work has advanced the development of new strategies to treat obesity and metabolic disorders, earning him recognition as a leader in the field.
Dr. Jonathan LongA respected scientist at Stanford University known for his innovative research in metabolic biology. His work explores how metabolites influence cellular processes and overall health. Dr. Long pioneered research on ketone body metabolism, revealing the mechanisms linking biochemical pathways to metabolic health. His research has practical implications for addressing obesity and related diseases. The joint efforts of Professor Xu and Dr. Long reveal new ways to combat metabolic diseases.
