A new study reveals that an oral nanotherapy could potentially reduce the small intestine’s ability to absorb fat, offering a promising approach to treat diet-related obesity. Although the therapy is still in its early stages, its success in humans could revolutionize obesity treatment.
In 2022, 43% of adults worldwide were classified as overweight, with 16% living with obesity. These conditions significantly increase the risk of developing type 2 diabetes, heart disease, and certain cancers. Despite years of research into fat metabolism, an effective method to inhibit fat absorption in the intestines has remained elusive. However, this recent study suggests a breakthrough using oral nanoparticles designed to target fat absorption directly.
Dr. Wentao Shao, a researcher at Tongji University’s School of Medicine in Shanghai and one of the study’s authors, explained, “For years, researchers have studied fat metabolism, but finding an effective way to block fat absorption has been difficult. Most strategies focus on reducing dietary fat intake, but our approach targets the body’s fat absorption process itself.”
The therapy centers on an enzyme called Sterol O-acyltransferase 2 (SOAT2), which plays a key role in fat absorption. SOAT2 is found in liver cells and cells lining the intestines. It has been well-studied for its involvement in atherosclerosis, but its role in fat absorption has been harder to address.
In the study, the researchers used nanoparticles containing small interfering RNAs (siRNAs), which are known for regulating gene expression. When taken orally, these nanoparticles are delivered to the small intestine, where they reduce the production of SOAT2, inhibiting fat absorption. In tests on mice, even those fed a high-fat diet absorbed less fat and avoided obesity.
“This treatment has several advantages,” Dr. Shao said. “It’s non-invasive, has low toxicity, and is likely to be better accepted by patients compared to existing obesity treatments, which are often invasive or hard to maintain.”
The researchers also uncovered the mechanism behind this inhibition. Reducing SOAT2 in the small intestine triggers the breakdown of CD36, a protein responsible for transporting fat. This process causes cellular stress, prompting the recruitment of an enzyme called E3 ligase RNF3, which accelerates the degradation of CD36.
Unlike previous studies that found liver fat buildup when SOAT2 was blocked in liver cells, this approach focuses on the intestine, avoiding the risk of liver complications.
“Targeting fat absorption in the intestines without affecting the liver is one of the most exciting aspects of this therapy,” said Professor Zhaoyan Jiang, also from Tongji University and co-corresponding author of the study. “This makes our treatment safer and more focused compared to previous methods.”
The researchers plan to continue testing the therapy in larger animal models before moving on to human trials. If successful, the nanotherapy could offer a new solution for managing obesity.
“We believe this nanoparticle system represents a major advancement in obesity treatment,” Professor Jiang said. “It tackles both fat metabolism and diet-related weight gain, potentially marking the beginning of a new era of more effective therapies.”
The study was presented at the United European Gastroenterology (UEG) Week 2024, one of the world’s leading gastroenterology conferences, and published in Advanced Science.
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