The study published in the journal Diabetes suggests that nobiletin, found in highest concentrations in the white pith of tangerines, may help to maintain healthy levels of cholesterol, glucose, and insulin, in addition to preventing the build up fat.
“Nobiletin-treated mice were basically protected from obesity … and in longer-term studies, nobiletin also protected these animals from atherosclerosis, the build up of plaque in arteries, which can lead to a heart attack or stroke,” said Dr Murray Huff, director of the vascular biology research group at the Robarts Research Institute, University of Western Ontario, USA.
Huff added that the study “really paves the way for future studies” to test the potential of nobiletin in reducing the risks of metabolic syndrome and related conditions.
However, Huff said that he suspects there is not enough nobiletin in tangerines to transfer the dramatic effects shown in mice into humans – adding that supplements would be most likely be needed.
Dr Huff's research has focused on the properties of naturally-occurring bioactive molecules. Two years ago, his research drew international attention when he discovered a flavonoid in grapefruit called naringenin offered similar protection against obesity and other signs of metabolic syndrome.
“What's really interesting to us is that nobiletin is ten times more potent in its protective effects compared to naringenin, and this time, we've also shown that nobiletin has the ability to protect against atherosclerosis,” said Huff.
Huff and his team evaluated the effects of nobiletin on lipoprotein (lipid transporting particle) secretion in cultured human hepatoma cells (HepG2) and in a mouse model of insulin resistance and atherosclerosis.
In human cells, nobiletin was shown to prevent the build up of fat by stimulating the expression of genes involved in burning excess fat, and inhibiting the genes responsible for manufacturing fat.
“Nobiletin restores glucose tolerance and insulin sensitivity in liver and peripheral tissues. Collectively, improvement in these metabolic parameters leads to the prevention of atherosclerosis,” wrote the authors.
However, a second group, in which nobiletin was administered with the western diet, gained a normal amount of weight and showed no rise in cholesterol, insulin or glucose.
The researchers observed that the nobiletin-fed mice were also more sensitive to insulin, and their livers were found to be less fatty.
“Our studies provide physiological and molecular evidence that nobiletin regulates hepatic lipid metabolism to prevent many of the abnormalities associated with insulin resistance … the correction of hepatic steatosis, dyslipidemia, and glucose homeostasis by nobiletin protects against the development of atherosclerosis through a range of mechanisms,” said the researchers.
Although not evaluated in the current study, the researchers suggested that a reduction in inflammation and foam cell (cells that form early in atherosclerosis) formation may also contribute to the attenuation of atherosclerosis.
Published online ahead of print, doi: 10.2337/db10-0589
“Nobiletin Attenuates VLDL Overproduction, Dyslipidemia, and Atherosclerosis in Mice With Diet-Induced Insulin Resistance”
Authors: E.E. Mulvihill, J.M. Assini, J.K. Lee, E.M. Allister, B.G. Sutherland, J.B. Koppes, et al