Scientists have revealed a new strategy to combat obesity, fat absorbed in the small intestine. This was published in Advance Science Journal.
Presented at UEG Week 2024, the research is specifically on an enzyme known as Sterol O-acyltransferase 2 (SOAT2), which plays a significant role in the small intestine fat absorption. As a result of this, the current study presents a therapeutic angle of suppressing this enzyme in the small intestine to prevent fat absorption and consequently obesity.
Although significant efforts have been made in understanding fat metabolism no potent inhibitors of intestinal fatty acid uptake has been developed so far.
“Thus, the fat metabolism has been under research for years but the problem was to find an effective method for blocking the fat absorption,” commented Dr Wentao Shao, the lead researcher. ”Most programmes are centered on the common perception of restraining the intake of fats in foods, whereas, our plan looks at the body’s ability to absorb fats directly.”
For the research team, the key was a delivery system based on the nanoparticles, a tiny capsule that has a polymer core and a protective shell.
The system was developed to effectively deliver small interfering RNA (siRNA) into the small intestine to down-regulate SOAT2 to impede fat digestion. Similarly, in mouse models the animals exposed to the nanoparticle therapy did not consume fats and consequently did not become obese even when they fed on a high fat diet.
“There are several advantages with this type of oral treatment,” Shao added. First, it is not invasive, second it is not very toxic, and it also seems to have a much better potential for better patient compliance compared with current obesity treatments which might be invasive or hard to stick to. This makes it a viable option.”
The study also established how SOAT2 influences fat absorption by identifying the detailed process of this function. Selective knockdown of SOAT2 in the small intestine leads to protein degradation of an important protein for fat transport known as CD36.
This process is associated with cell stress and the binding of E3 ligase RNF5 to CD36, an enzyme that promotes degradation of the receptor.
Prior research has shown that hepatic knock out SOAT2 results in the storage of fat in the liver which is not an intended goal with this new method that utilizes an intestine specific approach thereby eliminating the dangerous side of blocking SOAT2 while giving effective treatment for obesity.
This is important because prior research demonstrated that hepatic deletion of SOAT2 resulted in fat accumulation in the liver, a consequence of our treatment that has not yet been addressed because we only knockdown intestinal SOAT2.
“We think that this nanoparticle system is indeed a breakthrough on obesity treatment and will be a new identified opportunity which can effectively control fat metabolism and address diet induced obesity, ‘ Professor Jiang added.
Reference:
United European Gastroenterology. Novel nanoparticle therapy targets fat absorption to combat obesity
