Mice fed a high-fat, high-cholesterol diet that were also given nobiletin, a flavonoid found in sweet oranges and tangerines, 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, according to a new study.
Nobiletin is a molecule found in sweet oranges and tangerines. Image credit: Gerhard Gellinger.
“We went on to show that we can also intervene with nobiletin,” said senior author Professor Murray Huff, a researcher at the University of Western Ontario.
“We’ve shown that in mice that already have all the negative symptoms of obesity, we can use nobelitin to reverse those symptoms, and even start to regress plaque build-up in the arteries, known as atherosclerosis.”
“But we still haven’t been able to pinpoint exactly how nobiletin works.”
The scientists hypothesized that the molecule was likely acting on the pathway that regulates how fat is handled in the body.
Called AMP-activated protein kinase (AMPK), this regulator turns on the machinery in the body that burns fats to create energy, and it also blocks the manufacture of fats.
However, when the authors studied nobiletin’s effects on mice that had been genetically modified to remove AMPK, the effects were the same.
“This result told us that nobiletin is not acting on AMPK, 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?” Professor Huff said.
While the mystery remains, this result is still clinically important because it shows that nobiletin won’t interfere with other drugs that act on the AMPK system.
“Current therapeutics for diabetes like metformin for example, work through this pathway,” Professor Huff said.
“The next step is to move these studies into humans to determine if nobiletin has the same positive metabolic effects in human trials.”
“Obesity and its resulting metabolic syndromes are a huge burden to our health care 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.”
The study was published in the Journal of Lipid Research.
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Nadya M. Morrow et al. 2020. The citrus flavonoid nobiletin confers protection from metabolic dysregulation in high-fat-fed mice independent of AMPK. Journal of Lipid Research 61: 387-402; doi: 10.1194/jlr.RA119000542
