The prevalence of obesity worldwide is approaching 16%. In France, as an adult, it exceeds 17%. While many options are now available and demonstrated to be effective in combating this major public health scourge, including the adoption of a healthy lifestyle, but also bariatric surgery and weight loss medications including “ new » GLP-1 agonists, new alternative approaches remain necessary.
New approach precisely targets fat absorption in the small intestine. The nanoparticle system is in fact designed to deliver therapeutic molecules directly to the digestive tract. The research provides its first evidence of effectiveness in preventing diet-induced obesity.
The study focuses on an enzyme called sterol O-acyltransferase 2 (SOAT2),
which plays an essential role in the absorption of fats in the small intestine. The approach involves inhibiting this enzyme in the small intestine, to reduce fat absorption and thus prevent obesity.
Lead author Dr Wentao Shao of Tongi University notes that “While most strategies focus on reducing dietary fat intake, the new approach directly targets the body’s fat absorption process”. That being said, this is not the first team to work in this way on fat metabolism, however, until now, no research has led to the identification of an effective inhibitor of intestinal absorption of fatty acids. in the intestine.
The team developed an innovative delivery system based on nanoparticles which efficiently transport small interfering RNAs (siRNAs) to the small intestine, where they go reduce SOAT2 expressionthereby inhibiting the absorption of fats.
The proof of concept is provided in vivo in animal models of obesity which, treated with nanoparticle therapy, in fact absorb less fat and avoid obesity, even when subjected to a high-fat diet.
This is indeed an oral treatment
Consequently, with all the advantages: non-invasive, low toxicity, good compliance with current treatments against obesity.
How does it work? Inhibition of SOAT2 in the small intestine triggers the degradation of CD36, a protein responsible for fat transport. This process involves both cellular stress and the recruitment of another enzyme (E3 ligase RNF5), which enhances CD36 degradation. This new understanding complements findings from previous research showing that blocking hepatic SOAT2 leads to fat accumulation in the liver.
It is therefore a new ability to target the absorption of fats in the intestines without affecting the liver, to be tested, initially, on large animal models then via clinical trials in humans.
This nanoparticle-based system could represent a major advance and a major new weapon in the still insufficient arsenal of therapies against obesity.
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