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Research from the Wei and Simcox Labs in the Department of Biochemistry investigates how a metabolite linked to obesity and type 2 diabetes is regulated. Here’s the run down on their latest research, published in the Journal of Biological Chemistry:
What background information do you need to know?
Metabolites are small molecules that are made, used, or modified during the body’s biochemical reactions. Primary metabolites, such as vitamins and animo acids, are essential to our survival. Secondary metabolites are not strictly essential, but they can still play important roles in health and disease. Many metabolites are available as dietary supplements to support general health, build muscle, enhance brain function, and help manage metabolic disorders such as obesity and diabetes.
One example is β-alanine, a precursor to vitamin B5 and carnosine that is sometimes used as a dietary supplement to enhance exercise performance. Biochemical reactions lead to modifications in β-alanine that produce other naturally occurring metabolites, including N-acetyl-β-alanine. Dysregulation of N-acetyl-β-alanine production or accumulation has been linked to obesity, type 2 diabetes, and kidney diseases, but the pathways that produce, regulate, and break down this metabolite are not yet well understood.
Why does this matter?
In recent years, drugs that serve as appetite suppressants (including GLP-1 receptor agonists like Ozempic) have been widely used to treat obesity-related conditions. However, these drugs can cause side effects, are costly, and their long-term effectiveness is still being studied. A deeper understanding of how the body regulates the production and breakdown of metabolites associated with obesity and other metabolic diseases, such as N-acetyl-β-alanine, could reveal new biological pathways involved in appetite and metabolism. These insights may eventually help guide the development of naturally occurring metabolite-based supplements or therapies for obesity, type 2 diabetes, and related conditions.
How have scientists made progress?
The Wei Lab, in collaboration with the Simcox Lab, identified that the enzyme PTER plays an essential role in breaking down N-acetyl-β-alanine through hydrolysis. (PTER is already known to mediate other metabolites that are associated with body mass index.) Mice lacking the gene to produce PTER exhibited an accumulation of N-acetyl-β-alanine. The researchers also found that giving an N-acetyl-β-alanine supplement to obese mice reduced their appetite and food intake.
The results point to promising future studies exploring whether natural metabolites can be used therapeutically to maintain and support healthy metabolic function. The researchers’ next steps will be to understand how N-acetyl-β-alanine suppresses appetite, identify other metabolites and metabolic functions involved in this pathway, and explore how N-acetyl-β-alanine is synthesized.
Written by Renata Solan.
In Research In Brief: The What, Why, and How, we explore new research from the UW–Madison Department of Biochemistry to learn more about the world around us — and inside us.
This edition of Research in Brief: The What, Why, and How is based on the following publication: Li, Fu, Lyu, Wang, Hassman, Shuster, Kizzar, Simcox, and Wei. Tissue-dependent enzymatic control of N-acetyl-β-alanine by PTER. J Biol Chem, May 24, 2026, 113191. This research was funded in part by the University of Wisconsin–Madison Department of Biochemistry, the National Institutes of Health (P30DK020579, R01DK133479, and 5T32GM140935), the National Institute of General Medical Sciences (5T32GM135066), and the Glenn Foundation and American Federation for Aging Research (A22068). Judith Simcox is an HHMI Freeman Hrabowski Scholar.