Diet | Latest Research | Obesity
New Pathway Linking Diet, Genetics, and Body Weight Identified in Stanford-Led Study
Potential for New Anti-Obesity Drugs Suggested by Findings
A new biochemical pathway linking diet, genetics, and body weight has been identified by Stanford Medicine researchers, suggesting the possibility of a new class of anti-obesity drugs. Conducted in mice, the study revealed a connection between the amino acid taurine and a previously unstudied gene called PTER, which has been associated with body weight.
This newly identified relationship highlights a metabolic pathway that regulates body weight, operating independently of the mechanisms used by existing weight loss drugs like Ozempic or Wegovy. The findings suggest that these approaches could potentially be used together to provide new options for weight management.
“This is an additional branch of a very complex system of feeding and body weight regulation,” it was noted by Jonathan Long, PhD, assistant professor of pathology at Stanford Medicine and senior author of the study. The study, published on August 7 in Nature, was led by Long and postdoctoral scholar Wei Wei, PhD.
Taurine, which is abundant in protein-rich foods like meat and shellfish, was the focus of the research. In mice, taurine supplementation has been shown to lower body weight and improve exercise performance.
Conversely, mice engineered to have low levels of taurine displayed muscle atrophy and reduced exercise capacity. The exact mechanisms by which taurine influences body weight, however, have remained unclear.
“Taurine does all sorts of stuff in our bodies and is metabolized in many different ways,” Long explained. “It’s a complicated soup.”
One metabolite of taurine, N-acetyltaurine, is formed when taurine combines with acetate. Levels of N-acetyltaurine in the body fluctuate in response to physiological changes such as endurance exercise and diet, which affect taurine and acetate levels.
The Identified Enzyme
While exploring taurine metabolism and its relationship to body weight, Wei and Long identified an enzyme called PTER (phosphotriesterase-related) that converts N-acetyl taurine back into taurine. This enzyme is part of a molecular seesaw that allows the body to respond to changes in diet, exercise, and other factors.
The PTER gene, part of a group associated with body mass index (BMI) in humans, has remained largely unstudied. Although mutations in another gene in this group, MC4R, are known to cause excessive hunger and are strongly linked to obesity, the function of PTER has been unclear.
“Despite this genetic association, the role of PTER in body weight regulation had not been understood,” it was noted by Long. “It was an orphan gene that encoded an orphan enzyme. Now we know that PTER breaks down, or hydrolyzes, N-acetyltaurine.”
Further research on mice in which the PTER gene had been knocked out revealed that these animals had higher levels of N-acetyltaurine in their blood and tissues compared to control mice. When these knockout mice were fed a high-fat diet and given taurine in their drinking water, they were found to eat less and weigh less than control animals after eight weeks. The reduction in body weight was attributed entirely to a decrease in fat mass.
To further investigate, N-acetyltaurine was administered directly to the mice, resulting in reduced body weight and food intake in both the knockout mice and control animals on a high-fat diet.
It was also found that the PTER pathway operates independently of the pathway used by GLP-1 receptor agonists, such as Ozempic, currently available for weight loss.
“This interaction of genetics and diet in regulating body weight represents a fundamental advance in understanding how diet affects weight and body composition,” Long stated.
But how is it produced in the body?
Interestingly, it remains unclear how N-acetyl taurine is produced in the body. There is speculation that the gut microbiome may play a role, as mice treated with antibiotics to reduce gut bacteria showed a 30% decrease in N-acetyl taurine levels.
“This possible role of the gut microbiome in N-acetyl taurine production is an intriguing area for future research,” Long noted. “It raises the possibility of probiotic or dietary interventions that could promote the formation of N-acetyl taurine to reduce body weight. However, much more work is needed in this area.”
Ongoing studies of PTER and taurine metabolites in humans are being conducted by Long and his colleagues, though the task is acknowledged to be challenging.
“All of the stuff we eat, and we eat a lot of stuff, can interact with our bodies at a molecular and genetic level,” Long said. “It’s not a simple code. But we’re starting to understand these intersecting pathways at a much more granular level than ever before.”
