New joint research by scientists at the Hebrew University of Jerusalem and Harvard University’s Massachusetts General Hospital (MGH) has demonstrated the mechanism by which a single compound in grapefruit controls fat and glucose metabolism, replacing multiple drugs. Naringenin, an antioxidant derived from the sour flavor of grapefruits and other citrus fruits, may cause the liver to break down fat while increasing sensitivity to insulin – a process that naturally occurs during long periods of fasting.

The US-Israeli team reports that naringenin activates a family of small proteins called nuclear receptors, causing the liver to break down fatty acids. In fact, the compound seems to mimic the actions of other drugs, such as the lipid-lowering fenofibrate and the anti-diabetic rosiglitazone, offering the advantages of both. If the results of this study extend to human patients, this dietary supplement could become a staple in the treatment of hyperlipidemia, type-2 diabetes and perhaps metabolic syndrome, the precursor of diabetes. The report appeared two weeks ago in the online journal PLoS (Public Library of Science) One.

“It’s a fascinating find,” says senior author Dr. Yaakov Nahmias of HU. “We show the mechanism by which naringenin increases two important pharmaceutical targets, PPAR alpha and PPAy, while blocking a third, LXR alpha. The results are similar to those induced by long periods of fasting.” The liver is the main organ responsible for the regulation of carbohydrate and lipid levels. Following a meal, the blood is flushed with sugars, which activate LXR alpha, causing the liver to create fatty acids for long-term storage. During fasting, the process is reversed; fatty acids are released by fat cells, activate PPAR alpha in the liver, and are broken down to ketones. A similar process, involving PPARy, increases sensitivity to insulin.

“It is a process which is similar to the Atkins diet, without many of the side effects,” says Dr. Martin Yarmush, director of the MGH Center for Engineering in Medicine and one of the paper’s authors.

“The liver behaves as if fasting, breaking down fatty acids instead of carbohydrates.”

“Dual PPAR alpha and PPARy agonists, like naringenin, were long sought by the pharmaceutical industry,” says Nahmias, “but their development was plagued by safety concerns. Remarkably, naringenin is a dietary supplement with a clear safety record. Evidence suggests it might actually protect the liver from damage.”

Grapefruit’s sour taste is caused the presence of the flavonoid naringin, which is broken down in the gut into naringenin.

Earlier evidence has shown the compound has cholesterol-lowering properties and may ameliorate some symptoms associated with diabetes. The researchers showed that the compound activates PPAR alpha and PPARy by dramatically increasing the levels of a coactivator peptide of both, called PGC1 alpha.

At the same time, naringenin bound directly to LXR alpha, blocking its activation. These effects culminated with increased fatty acid oxidation and the inhibition of LDL (“bad cholesterol”) production.

ISRAELIS HONORED

Two Israelis were recently presented with very prestigious awards. Prof. Alberto Gabizon, chief of oncology at Jerusalem’s Shaare Zedek Medical Center, has received the 2010 Alec Bangham Lifetime Achievement Award at the Liposome Research Days Conference in Vancouver, Canada. Since its inception 17 years ago, the conference has been the leading gathering of the international liposome research community. Liposomes are tiny globules of fat that can be used to deliver drugs more effectively. Gabizon was cited for his outstanding contributions to liposome technology. In 1998, fellow Israeli Prof.

Yechekel Barenholz – who with Gabizon codeveloped the widely used cancer drug Doxil – received the same award.

Meanwhile, Prof. Lea Baider of Hadassah University Medical Center was the only Israeli to receive an award of the International Psycho-Oncology Society for her outstanding work on the psychological aspects of cancer and promoting awareness of the relevance of life quality for cancer patients and their families. Founded in 1984, the society was created to foster international multidisciplinary communication about clinical, educational and research issues that relate to psycho-oncology and psychosocial dimensions of cancer. Its members include over 5,000 professionals in over 40 countries.

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