Researchers from the Schulich School of Medicine & Dentistry reaffirmed previous findings that mice fed a high-fat, high-cholesterol diet were noticeably leaner and had reduced levels of insulin resistance and blood fats if they were also given the fruit-derived molecule nobiletin.
The study, published in the Journal of Lipid Research, saw researchers test their theory that the flavonoid acts on the pathway that regulates how fat is handled in the body. This regulator, called AMP Kinase, 'turns on' the machinery in the body that burns fats to create energy, and blocks the manufacture of fats.
However, when the researchers studied nobiletin's effects on mice genetically modified to remove AMP Kinase, the effects of the flavonoid were the same. The team were therefore unable to pinpoint the mechanism.
This recent result is still clinically important because it shows that nobiletin won't interfere with other drugs that act on the AMP Kinase system. Current therapeutics for diabetes like metformin, for example, work through this pathway.
Schulich professor Murray Huff, who has been studying nobiletin's effects for more than a decade, said: "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.
"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."
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," added Huff.
"We need to continue this emphasis on the discovery of new therapeutics."
Source: Journal of Lipid Research
Huff. M. W., et al
"The citrus flavonoid nobiletin confers protection from metabolic dysregulation in high-fat-fed mice independent of AMPK"