Researchers from Tongji University and Nanjing Medical University have unveiled a groundbreaking strategy aimed at addressing obesity by focusing on fat absorption within the small intestine. This advanced nanoparticle system, crafted to deliver therapeutic molecules directly to the digestive tract, has shown promising results in preventing obesity related to dietary habits.
Targeting Fat Absorption for Effective Weight Management
The findings, presented at UEG Week 2024, center on the enzyme Sterol O-acyltransferase 2 (SOAT2), a crucial player in the fat absorption process in the small intestine. By inhibiting this enzyme, the research proposes a novel therapeutic approach to decrease fat absorption and potentially prevent obesity.
While extensive research has been conducted on fat metabolism, identifying effective inhibitors of intestinal fatty acid absorption has long posed a challenge.
“For years, our studies on fat metabolism have struggled to find efficient ways to obstruct fat absorption,” said Dr. Wentao Shao, lead researcher at Tongji University. “Most strategies focus on reducing dietary fat intake, but our approach directly targets the body’s fat absorption mechanisms.”
Innovative Nanoparticle Delivery System
The research team developed an innovative nanoparticle delivery system, featuring a polymer core encapsulated by a protective shell. This system effectively transports small interfering RNAs (siRNAs) to the small intestine, where they function to lower SOAT2 expression, thereby inhibiting fat absorption.
In experiments with mouse models, subjects treated with this nanoparticle therapy exhibited decreased fat absorption and managed to avoid obesity, even while consuming a high-fat diet.
“This oral treatment presents numerous advantages: it is non-invasive, exhibits low toxicity, and has a high likelihood of better patient compliance compared to existing obesity treatments, which are often invasive or difficult to maintain,” Dr. Shao noted, emphasizing the potential of this method.
Mechanisms Behind SOAT2 Regulation
The study also uncovered the mechanism by which SOAT2 regulates fat absorption. When SOAT2 is inhibited in the small intestine, it triggers the degradation of CD36, a protein responsible for fat transport. This process includes the induction of cellular stress and the recruitment of the enzyme E3 ligase RNF5, which accelerates the degradation of CD36.
Prior studies have shown that blocking SOAT2 in the liver can result in fat accumulation. However, this approach, which specifically targets the intestine, avoids that risk, presenting a safer and more focused treatment option for obesity.
“One of the most exciting aspects of this therapy is its ability to specifically target fat absorption in the intestines while sparing the liver,” stated Zhaoyan Jiang, Professor and study supervisor at Shanghai East Hospital. “This focus is critical because previous research indicated that inhibiting SOAT2 in the liver could lead to fat buildup—a risk our treatment circumvents by concentrating solely on intestinal SOAT2.”
Next Steps in Research
The study team plans to further investigate the nanoparticle system in larger animal models to validate its efficacy and safety for potential human application.
“We believe this nanoparticle system represents a significant advancement in obesity management, offering a new solution that addresses both fat metabolism and diet-related weight gain, which may herald a new era of more effective treatments,” concluded Professor Jiang.
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