Fat absorption therapy could help prevent obesity

Researchers hope therapy could reduce cases of related health complications including type 2 diabetes.

A new approach to tackle obesity by targeting fat absorption in the small intestine has been unveiled by researchers.

The cutting-edge nanoparticle system, engineered to deliver therapeutic molecules directly to the digestive tract, has shown significant potential to prevent diet-induced obesity.

Researchers from China presented their findings at the recent United European Gastroenterology (UEG) Week in Vienna.

The study focused on an enzyme called sterol O-acyltransferase 2 (SOAT2), which plays a critical role in fat absorption in the small intestine. By inhibiting this enzyme in the small intestine, the study offers a promising therapeutic approach to reduce fat absorption and potentially prevent obesity and related health complications, including type 2 diabetes.

Effective inhibitors of intestinal fatty acid uptake have remained elusive in previous studies into fat metabolism, despite extensive research.

Dr Wentao Shao, PhD candidate specialising in basic medical research at the Center of Gallstone Disease, Shanghai East Hospital, Tongji University, China and lead researcher, said: “For years, researchers have studied fat metabolism, but finding an effective way to block fat absorption has been difficult. While most strategies focus on reducing dietary fat intake, our approach targets the body’s fat absorption process directly."

The research team developed an innovative delivery system using nanoparticles – a tiny capsule made from a polymer core, coated in a protective shell. The system was designed to efficiently carry small interfering RNAs (siRNAs) to the small intestine, where they can reduce SOAT2 expression, inhibiting fat absorption. In tests, study models treated with the nanoparticle therapy absorbed less fat and avoided obesity, even on a high-fat diet.”

Dr Shao added: “This oral treatment offers several advantages. It is non-invasive, has low toxicity, and it has high potential for better patient compliance compared to current obesity treatments, which are often invasive or difficult to maintain. This makes it a promising alternative.”

The study also uncovered the underlying mechanism by which SOAT2 regulates fat absorption. Inhibition of SOAT2 in the small intestine triggers degradation of CD36, a protein responsible for transporting fat.

Previous studies have shown that blocking hepatic SOAT2 can lead to fat accumulation in the liver, whereas researchers believed their intestine-specific approach circumvents that risk, offering a safer and more focused treatment for obesity.

Professor Zhaoyan Jiang, study supervisor, said: “One of the most exciting aspects of this therapy is its ability to target fat absorption in the intestines without affecting the liver. This is important because previous studies showed that blocking SOAT2 in the liver can lead to fat build-up there – a risk our treatment avoids by focusing only on intestinal SOAT2.”

The research team plans to continue tests with the nanoparticle system to confirm its effectiveness and safety for potential use in humans.

Professor Jiang added: “We believe that this nanoparticle system represents a breakthrough in obesity management, offering a new solution that tackles both fat metabolism and diet-related weight gain, potentially ushering in a new era of more effective treatments.”

The UEG, founded in 1992, is a non-profit organisation for excellence in digestive health in Europe and beyond with its headquarters in Vienna.

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