Diet, weight, and metabolism are intricately linked, so studying their relationship is no easy task. People’s eating habits encompass a wide variety of foods, many of which are shared between different types of diets; this complexity makes it difficult to establish cause and effect. “What should you eat? What should you not eat?” mused Jonathan Long, a biochemist at Stanford University. To tackle this challenge, Long focuses on isolating single, chemically well-defined components of diets to better understand their impact on the body. 

Taurine, an amino acid commonly found in meats, shellfish, and energy drinks, is a regular part of many diets. While humans naturally produce taurine, dietary taurine can support the immune system and improve cardiovascular health. It is often used as a supplement for weight loss or to enhance exercise performance. Given taurine’s involvement in various physiological functions, researchers have been keen to understand how it is metabolized in the body, as it is converted into different taurine-containing molecules. This prompted Long to explore its metabolic pathways and he homed in on an understudied taurine metabolite called N-acetyltaurine.¹

N-acetyltaurine, formed when taurine binds to acetate during taurine degradation, can fluctuate in response to diet and exercise. However, the details of its breakdown process and potential functions remain unclear. The researchers were particularly interested in how this molecule might relate to issues such as energy balance or obesity. While investigating this gap, the researchers identified an enzyme responsible for breaking down N-acetyltaurine and linked this pathway to body weight regulation. Their findings, published in Nature, revealed that mice lacking this enzyme accumulated high levels of N-acetyltaurine and when fed a high-fat diet, resisted diet-induced obesity.² The work suggests the taurine metabolism pathway could help regulate body weight and food intake, highlighting its potential as a target for developing new weight-loss drugs similar to Ozempic.

Long’s fascination with metabolism stems from its role in how the body processes food and converts it into energy—a process that impacts health, aging, and weight. In exploring metabolites, he came across taurine, a surprisingly abundant yet understudied compound found in foods like shellfish, meat, and energy drinks. The lack of research on taurine intrigued him.

He remarked, “It’s kind of interesting and unusual for something [like taurine] that’s so abundant and prevalent in the foods we eat, but there’s actually very little understood about how that affects our bodies.” To better understand the relationship between diet and its potential effects on weight, he tackled the question from a chemical perspective.

To do this, the researchers used an old-school biochemistry approach to find the enzyme, or enzymes, responsible for regulating N-acetyltaurine. “We didn’t know where it would be,” explained Long. They ground up and purified enzymatic products from different mouse organs, looking for products of N-acetyltaurine degradation: acetate and taurine. Then, the researchers used chromatography to separate the enzymatic products and search for spikes in hydrolysis activity, which helped them identify three enzyme candidates. Of these candidates, the researchers found that an orphan enzyme called phosphotriesterase-related (PTER) was necessary for N-acetyltaurine hydrolysis. 

A previous large-scale genetic study had suggested that the PTER gene was linked to body weight in people, but almost nothing was known about the enzyme itself.³ This spurred Long to figure out the connection between the two.

To investigate the physiological relevance of PTER, the researchers used a Pter knockout (KO) mouse model. Across all tissues, mice without PTER developed N-acetyltaurine levels that Long described as, “through the roof” compared to wild type animals. Long wondered how this characteristic would affect body weight regulation in mice on a high-fat diet.

While humans consume varying amounts of taurine in their diets, standard mouse chow typically lacks taurine. Since taurine is a component of PTER activity, the researchers added it to the drinking water of Pter KO and wild type mice while feeding them a high-fat diet. After eight weeks, Pter KO mice ate less and resisted diet-induced obesity. These mice also showed improved glucose tolerance and insulin sensitivity compared to wild type mice, likely due to this leanness. However, Pter KO mice fed standard chow showed no changes in weight or food intake, regardless of taurine supplementation. These findings, Long remarked, support a gene-environment interaction, in which the Pter gene interacts with dietary taurine and the relationship with body weight becomes apparent in the presence of an environmental stimulus, such as a high-fat diet.

Chi Chen, a nutritional biochemist at the University of Minnesota who characterized N-acetyltaurine a decade ago as a biomarker for ethanol metabolism, remarked that he was glad to see other groups demonstrating the importance of this compound. He commented that this work has an interesting angle to be translated into pharmacological applications. “One thing that’s attractive is [that] this is an endogenous compound, so in a way, you could consider it as safe and not worry as much about side effects.”

Long echoed the idea of leveraging these findings for treatments in body weight regulation and added, “The fact that this Pter gene is related to body weight control, at least in the mouse, may lead to the development of PTER inhibitors that target this pathway and complement weight loss drugs like Ozempic.”