Western Ontario, Canada—Researchers at the University of Western Ontarioare studying a molecule called nobiletin, found in sweet oranges and tangerines, which they have found to drastically reduce obesity and reverse its negative side effects. They don’t, however, understand why it works.

According to a press release, mice fed a high-fat, high-cholesterol diet, and nobiletin were noticeably leaner and had reduced levels of insulin resistance and blood fats compared to mice that were fed a high-fat, high-cholesterol diet alone. Murray Huff, Ph.D., a Professor at Western’s Schulich School of Medicine & Dentistry who has been studying nobiletin for over a decade, added: “We went on to show that we can also intervene with nobiletin. We’ve shown that in mice that already have all the negative symptoms of obesity, we can use nobiletin to reverse those symptoms, and even start to regress plaque buildup in the arteries.”
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However, they still don’t know why it works—but they’ve eliminated one major hypothesis, and that’s a good sign. The pathway that regulates fat in the body, called AMP Kinase, turns on the machinery in the body that burns fats to create energy, and it blocks the manufacture of fats. Researchers hypothesized that nobiletin worked on that pathway—but when they gave nobiletin to mice genetically modified to have no AMP Kinase, the effects were the same, the press release says. Huff noted: “This result told us that nobiletin is not acting on AMP Kinase, and is bypassing this major regulator of how fat is used in the body. What it still leaves us with is the question—how is nobiletin doing this?” What itdoesmean is that nobiletin won’t interfere with other drugs that act on the AMP Kinase system, including metformin, which treats diabetes.

The next step, Huff says, is to begin performing these studies on humans, to determine if nobiletin has the same positive metabolic effects. “Obesity and its resulting metabolic syndromes are a huge burden to our healthcare system, and we have very few interventions that have been shown to work effectively. We need to continue this emphasis on the discovery of new therapeutics.”