Locking up Fats in CAGEs to Treat Obesity

A review of:

Brownell, Lindsay. “Locking up Fats in CAGEs to Treat Obesity.” Wyss Institute for Biologically Inspired Engineering, 26 Nov. 2019, wyss.harvard.edu/news/locking-up-fats-in-cages-to-treat-obesity/.

In “Locking up Fats in CAGEs to Treat Obesity” Lindsay Brownell described a new study from Harvard’s Wyss Institute for Biologically Inspired Engineering and John A. Paulson School for Engineering and Applied Sciences (SEAS). The study found that if Choline and Geranate (CAGE) is orally administered, it can physically reduce the absorption of fats from food. CAGE is a liquid salt that was originally created several years ago by Samir Mitragotri as part of an effort to improve medicine absorption by the human body. During that study, it became clear that the uptake of small hydrophobic molecules was not aided by CAGE. The researchers of the study suspected that CAGE was somehow binding to those molecules and preventing them from getting absorbed. “That observation led us to wonder if there were any contexts in which we would want to prevent the uptake of this type of molecule. We realized that fats are small and hydrophobic, and that CAGE could potentially be of interest as a medical treatment for obesity,” said Mitragotri, who is also a professor of bioengineering. The team first tested the impacts of CAGE on fats by mixing it with DHA, an omega-3 fat and water. They then tested the DHA-CAGE solution to healthy rat intestines ex vivo, before moving on to testing CAGE in living organisms. Capsules containing the DHA-CAGE solution was orally fed to living rats. After six hours, the researchers found that only half of the DHA was absorbed into the bloodstream, as compared to when the rats were fed DHA alone. Further tests were performed on the rats, and Mitragotri’s team learned that rats gained 12% less weight on a high fat diet with CAGE than rats on the same diet that were not given CAGE. Most importantly, during the month-long tests with CAGE, there were no side effects observed in the treated rats - no signs of inflammation and no changes in organ structure or function.

This research has the potential to be developed further and to help many people struggling with weight issues. Over one third of American adults are affected by obesity, a condition which also increases the risk of other diseases - high blood pressure, diabetes, asthma, to name a few - which can often be fatal. Obesity is a growing epidemic, and is one of the most significant public health threats. The cost of treating obesity and obesity-related diseases is expected to double every decade. Further testing with CAGE may lead to a widespread solution that would help with the epidemic. “This is the first proof-of-concept that orally administered ionic liquids can help reduce fat uptake and body mass, and this approach has significant clinical potential given that it is simple, fast, and much less invasive than liposuction or bariatric surgery and, because its mechanism of action is physical rather than chemical, it lacks the side effects observed with other drugs,” said Mitragotri.

Brownell’s article was well written, informative, and impactful - a necessary combination for exposure. The article was interesting, and structured in a way that holds a reader’s attention. It’s only weakness was a lack of the researcher’s actual data. There were no data tables or images of the experimental setup, nor images of the proposed molecular molecular bonding between CAGE and fat molecules. Brownell’s article shared the researchers’ sentiments with the readers, a move that also keeps readers aware of the researchers’ intentions and makes the article more powerful. “Our goal is to translate this work into a product that can help people maintain a healthier weight, and this study marks the very beginning of that journey”(M.D. Nurrunabi).