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)
“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
Grapefruit’s sour taste is caused the presence of the flavonoid
naringin, which is broken down in the gut into naringenin.
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,
oncology at Jerusalem’s Shaare Zedek Medical Center, has received the
Bangham Lifetime Achievement Award at the Liposome Research Days
Vancouver, Canada. Since its inception 17 years ago, the conference has
leading gathering of the international liposome research community.
are tiny globules of fat that can be used to deliver drugs more
Gabizon was cited for his outstanding contributions to liposome
1998, fellow Israeli Prof.
Yechekel Barenholz – who with Gabizon
codeveloped the widely used cancer drug Doxil – received the same
Meanwhile, Prof. Lea Baider of Hadassah University Medical Center
was the only Israeli to receive an award of the International
Society for her outstanding work on the psychological aspects of cancer
promoting awareness of the relevance of life quality for cancer patients
their families. Founded in 1984, the society was created to foster
multidisciplinary communication about clinical, educational and research
that relate to psycho-oncology and psychosocial dimensions of cancer.
members include over 5,000 professionals in over 40 countries.