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Innovative Nanoparticle Therapy Offers New Approach to Obesity Management
In a significant development in the fight against obesity, researchers have introduced an innovative strategy aimed at reducing fat absorption in the small intestine. This pioneering nanoparticle system, designed to transport therapeutic molecules directly to the digestive system, demonstrates considerable promise in preventing obesity induced by dietary habits. Findings related to this research have been detailed in a study published in the journal Advanced Science.
Targeting SOAT2 Enzyme for Weight Management
Presented during UEG Week 2024, the study centers on the enzyme Sterol O-acyltransferase 2 (SOAT2), a key player in the fat absorption process of the small intestine. By inhibiting this enzyme, researchers propose a novel therapeutic pathway capable of diminishing fat absorption, potentially mitigating obesity prevalence.
Historically, the quest for effective inhibitors of fatty acid uptake in the intestine has proven challenging. “Despite extensive studies on fat metabolism, blocking fat absorption effectively has eluded researchers,” noted Dr. Wentao Shao, the lead investigator. “Conventional methods primarily focus on reducing dietary fat intake; our strategy, however, zeroes in on the body’s absorption mechanism directly.”
Advancements in Nanoparticle Delivery Systems
The research team has crafted a sophisticated delivery method utilizing nanoparticles—minute capsules composed of a polymer core encased in a protective shell. This system adeptly transports small interfering RNAs (siRNAs) to the small intestine, targeting and suppressing SOAT2 expression, which results in decreased fat absorption. Remarkably, in trials with mouse models, those treated with this nanoparticle therapy exhibited lower fat absorption and successfully maintained weight, even when exposed to high-fat diets.
Advantages of the Novel Treatment
“This oral treatment presents numerous benefits,” Dr. Shao commented. “It is non-invasive, exhibits low toxicity, and offers improved patient compliance over existing obesity therapies, many of which are invasive or hard to adhere to. This makes our method a viable alternative.”
Understanding the Mechanism of Action
Intriguingly, the research also elucidated the mechanism by which SOAT2 modulates fat absorption. When SOAT2 is inhibited in the small intestine, it initiates the degradation of CD36, a protein that facilitates fat transport. This process is mediated through cellular stress and the involvement of E3 ligase RNF5, an enzyme that promotes CD36 breakdown.
Prior research indicated that obstructing hepatic SOAT2 can lead to fat accumulation in the liver. However, this study’s focus on intestinal SOAT2 presents a safer and more targeted method for obesity treatment.
Professor Zhaoyan Jiang, who supervised the study, emphasized, “One of the most appealing features of this therapy is its capacity to diminish fat absorption in the intestines without impacting liver function. This is crucial, given that prior studies have demonstrated the risk of fat buildup in the liver when SOAT2 is inhibited there; our approach circumvents this issue by specifically targeting SOAT2 in the intestines.”
Future Directions
The research team is set to explore the nanoparticle system’s efficacy and safety in larger animal models to further assess its potential for human applications.
Professor Jiang concluded, “We are optimistic that this nanoparticle system heralds a breakthrough in obesity treatment, providing a new methodology for addressing both fat metabolism and weight gain associated with diet, potentially ushering in a more effective treatment era.”
More information: Jingjia Liang et al, siRNA/CS‐PLGA Nanoparticle System Targeting Knockdown Intestinal SOAT2 Reduced Intestinal Lipid Uptake and Alleviated Obesity, Advanced Science (2024). DOI: 10.1002/advs.202403442
Source
phys.org