Canadian researchers report that a substance they discovered in tangerines prevented obesity in mice fed a junky diet.
Better yet, it produced metabolic changes that should reduce the risk of developing diabetes and discourage atherosclerosis … the underlying condition responsible for most heart disease.
The study was led by Murray Huff, a vascular biologist at The University of Western Ontario’s School of Medicine.
Two years ago, Huff’s lab drew international attention when they discovered a flavonoid in grapefruit called Naringenin, which also offered protection against obesity and other signs of metabolic syndrome in mice (Mulvihill EE et al. 2009).
(Flavonoids constitute most of the antioxidants in plant foods … they’re a subset of the larger group of plant-source antioxidants called polyphenols.)
And, as Huff says, “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.” (UWO 2011)
Tangerine agent seen as potential ally against diabetes and heart disease
The study employed mice genetically prone to developing metabolic syndrome in response to sugary, starchy, fatty diets (Mulvihill EE et al. 2009).
People and animals are said to have metabolic syndrome when they show any three out of six undesirable signs linked to diabetes and heart disease:
Abdominal obesity (excessive fat tissue in and around the abdomen).
High blood triglycerides, low HDL cholesterol and high LDL cholesterol: a state that fosters plaque buildups in artery walls.
Elevated blood pressure.
Insulin resistance or glucose intolerance (the body can’t properly use insulin or blood sugar).
Pro-thrombotic state that promotes dangerous clots (e.g., high fibrinogen or plasminogen activator inhibitor–1 in the blood).
Pro-inflammatory state (e.g., elevated C-reactive protein in the blood).
The mice were divided into two groups, both of which were fed a “western” diet high in fats and sugars … but one group had Nobiletin added to their chow.
The control group became obese and showed all the signs associated with metabolic syndrome: elevated cholesterol and triglycerides, high blood levels of insulin and glucose, and a fatty liver.
These metabolic abnormalities greatly increase the risk of cardiovascular disease and type 2 diabetes.
The second group of mice, fed the exact same diet but with Nobiletin added, experienced no rise in their levels of cholesterol, triglycerides, insulin or glucose, and gained weight normally.
The Nobiletin-fed mice also became much more sensitive to the effects of insulin … a good thing.
Nobiletin was shown to prevent the buildup of fat in the liver by stimulating the expression of genes involved in burning excess fat, and inhibiting the genes responsible for manufacturing fat.
“The Nobiletin-treated mice were basically protected from obesity,” said Dr. Huff. “And in longer-term studies, Nobiletin also protected these animals from atherosclerosis, the buildup of plaque in arteries, which can lead to a heart attack or stroke.”
Genetic effects support findings; human potential seen
When the team exposed isolated mouse cells to Nobiletin, they detected “nutrigenomic” effects that explain the metabolic protections it produced in the animal’s bodies.
Huff went on to note the experiments’ human implications: “This study really paves the way for future studies to see if this is a suitable treatment for metabolic syndrome and related conditions in people.”
That prospect for drug development probably helps explain why, although most of the funding came from the Heart and Stroke Foundation of Ontario, the research was funded in part by the Pfizer Corporation’s Canada Cardiovascular Research Program.
Whether or not a drug based on Nobiletin ever sees the light of day, it will still make sense for most people to favor the whole tangerine fruit, which contains many other beneficial antioxidants as well as fiber.
Plus, it’ll be free of side effects, and will always taste far better than any pill!
Mulvihill EE, Assini JM, Lee JK, Allister EM, Sutherland BG, Koppes JB, Sawyez CG, Edwards JY, Telford DE, Charbonneau A, St-Pierre P, Marette A, Huff MW. Nobiletin Attenuates VLDL Overproduction, Dyslipidemia, and Atherosclerosis in Mice With Diet-Induced Insulin Resistance. Diabetes. 2011 Apr 6. [Epub ahead of print]
Mulvihill EE, Allister EM, Sutherland BG, Telford DE, Sawyez CG, Edwards JY, Markle JM, Hegele RA, Huff MW. Naringenin prevents dyslipidemia, apolipoprotein B overproduction, and hyperinsulinemia in LDL receptor-null mice with diet-induced insulin resistance. Diabetes. 2009 Oct;58(10):2198-210. Epub 2009 Jul 10.
Schulich School of Medicine & Dentistry, The University of Western Ontario (UWO). Substance in tangerines fights obesity and protects against heart disease. April 6th, 2011. Accessed at