Blocking a key gut enzyme could help treat obesity

Scientists have discovered a new way to tackle obesity by blocking a gut enzyme that helps absorb fat. The enzyme, called SOAT2, plays a role in packaging cholesterol and fatty acids for absorption. When researchers genetically removed SOAT2 from the intestines of mice, the animals absorbed less fat and were protected from diet-induced obesity.

To translate this finding into a treatment, the team developed a nanoparticle-based system to deliver small interfering RNA (siRNA) to the gut, which silences the Soat2 gene. This targeted approach successfully reduced fat absorption and prevented obesity in mice. Further experiments revealed that blocking SOAT2 triggers stress responses in intestinal cells, leading to the breakdown of CD36, a key protein involved in fat uptake.

The findings suggest that targeting SOAT2 in the gut could be a promising strategy for obesity treatment, offering a potential new avenue for siRNA-based therapies.

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Reference: Zhaoyan Jiang, Aihua Gu, et al., siRNA/CS-PLGA Nanoparticle System Targeting Knockdown Intestinal SOAT2 Reduced Intestinal Lipid Uptake and Alleviated Obesity, Advanced Science (2025). DOI: 10.1002/advs.202403442