Researchers from Tongji University and Nanjing Medical University have developed an innovative method to address obesity by focusing on fat absorption in the small intestine. This advanced nanoparticle system, designed to deliver therapeutic molecules directly to the digestive system, has demonstrated promising results in preventing obesity caused by diet
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The study, which was presented at UEG Week 2024, focuses on the enzyme Sterol O-acyltransferase 2 (SOAT2), which is essential in the process of fat absorption in the small intestine. By targeting and inhibiting this enzyme, the research offers a novel therapeutic strategy to reduce fat absorption and potentially prevent obesity.
While fat metabolism has been extensively studied, finding effective inhibitors of intestinal fatty acid absorption has proven challenging until now.
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.
Dr. Wentao Shao, Lead Researcher, Tongji University
The research team designed an innovative nanoparticle delivery system, consisting of a polymer core encapsulated within a protective shell. This system was engineered to efficiently transport small interfering RNAs (siRNAs) to the small intestine, where they work to reduce SOAT2 expression, thereby inhibiting fat absorption.
In mouse models, the animals treated with this nanoparticle therapy showed reduced fat absorption and were able to avoid obesity, even when consuming a high-fat diet.
This oral treatment offers several advantages. It is non-invasive, has low toxicity, and has a 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.
Dr. Wentao Shao, Lead Researcher, Tongji University
The study also revealed the mechanism by which SOAT2 regulates fat absorption. Inhibiting SOAT2 in the small intestine initiates the degradation of CD36, a protein responsible for fat transport. This process involves inducing cellular stress and recruiting the enzyme E3 ligase RNF5, which accelerates CD36 degradation.
Previous research has demonstrated that blocking SOAT2 in the liver can result in fat accumulation, but this intestine-specific approach prevents that risk, providing a safer and more targeted treatment for obesity.
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 buildup – a risk our treatment avoids by focusing only on intestinal SOAT2.
Zhaoyan Jiang, Professor and Study Supervisor, Shanghai East Hospital
The study team intends to test the nanoparticle system in larger animal models in the future to verify its efficacy and safety for possible human use.
“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,” Professor Jiang concluded.
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