Grapefruit's Antioxidant Ingredients Beneficial for Diabetes Therapy

Naringenin, an antioxidant derived
from the bitter flavor of grapefruits
and other citrus fruits, may cause
the liver to break down fat while
increasing insulin sensitivity,
a process that naturally occurs
during long periods of fasting.

A team of researchers from the Hebrew University of Jerusalem
and Massachusetts General Hospital (MGH) report 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 report appears in this week issue of
the online journal PLoS ONE.

"It is a fascinating find," said the researchers of the Hebrew
University of Jerusalem "We show the mechanism by which
naringenin increases two important pharmaceutical targets,
PPARα and PPARγ, while blocking a third, LXRα. 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 in the blood. Following a meal, the
blood is flushed with sugars, which activate LXRα, 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 PPARα in the liver, and are broken down to ketones.
A similar process, involving PPARγ, increases sensitivity
to insulin.

"It is a process which is similar to the Atkins diet, without many
of the side effects," they added... "The liver behaves as if fasting,
breaking down fatty acids instead of carbohydrates."

"Dual PPARα and PPARγ agonists, like naringenin, were
long sought after by the pharmaceutical industry, but their
development was plagued by safety concerns. Interestingly,
naringenin is a dietary supplement with a clear safety record.
Evidence suggests it might actually protect the liver from
damage."

Grapefruit's bitter 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 of the symptoms
associated with diabetes. The researchers demonstrated that
the compound activates PPARα and PPARγ by dramatically
increasing the levels of a co-activator peptide of both, called
PGC1α. At the same time, naringenin bound directly to LXRα,
blocking its activation. These effects culminated with increased
fatty acid oxidation and the inhibition of vLDL ('bad cholesterol') production.

The research was supported by grants from the National
Institutes of Health (NIH) and European Research Council
(ERC).

This work was supported by the National Institute of Diabetes
and Digestive and Kidney Diseases (K01DK080241), a
European Research Council starting grant (TMIHCV 242699),
and the Harvard Clinical Nutrition Research Center
(P30-DK040561). Resources were provided by the BioMEMS
Resource Center (P41 EB-002503), Shriners Burns Hospital,
and the Alexander Silberman Institute of Life Sciences.


Journal Reference:
"Transcriptional Regulation of Human and Rat Hepatic Lipid
Metabolism by the Grapefruit Flavonoid Naringenin"

Public Library of Science (2010, August 27). Grapefruit's
bitter taste holds a sweet promise for diabetes therapy.