Grapefruit tegen overgewicht en diabetes*
Uit een Israëlisch-Amerikaanse studie blijkt dat de bioactieve stof in grapefruit,
naringenine zorgt dat in de lever vet afgebroken wordt en de gevoeligheid voor insuline verhoogd wordt. Iets wat normaal gebeurt tijdens een lange periode van vasten. Naringenine is de stof die een bittere smaak geeft aan grapefruit. De manier waarop naringenine dit doet is te vergelijken met de manier zoals medicijnen als fibraten om de
triglyceriden te verlagen en thiazolidinedion-geneesmiddelen zoals rosiglitazon en pioglitazon voor de behandeling van
diabetes type 2 dit doen. Naringenine doet dit wel zonder enige bijwerking.
Grapefruit's Bitter Taste Holds A Sweet Promise 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," says Yaakov Nahmias, PhD, of the Hebrew University of Jerusalem the paper's senior author. "We show the mechanism by which naringenin increases two important pharmaceutical targets, PPARa and PPAR?, while blocking a third, LXRa. 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 LXRa, 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 PPARa in the liver, and are broken down to ketones. A similar process, involving PPAR?, increases sensitivity to insulin.
"It is a process which is similar to the Atkins diet, without many of the side effects," says Martin L. Yarmush, MD, PhD, 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." Yarmush is the Helen Andrus Benedict Professor of Surgery and Bioengineering at Harvard Medical School.
"Dual PPARa and PPAR? agonists, like naringenin, were long sought after 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 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 PPARa and PPAR? by dramatically increasing the levels of a co-activator peptide of both, called PGC1a. At the same time, naringenin bound directly to LXRa, blocking its activation. These effects culminated with increased fatty acid oxidation and the inhibition of vLDL ('bad cholesterol') production.
Additional co-authors of the PLoS ONE paper are Jonathan Goldwasser, PhD, Eric Yang, PhD, MGH; Pazit Cohen, PhD, Hebrew University; and Patrick Balaguer, PhD, INSERM Univ. Montpellier France. The work was supported by grants from the National Institutes of Health (NIH) and European Research Council (ERC).
Citation:
Goldwasser J, Cohen PY, Yang E, Balaguer P, Yarmush ML, et al. (2010) Transcriptional Regulation of Human and Rat Hepatic Lipid Metabolism by the Grapefruit Flavonoid Naringenin: Role of PPARa, PPARc and LXRa. PLoS ONE 5(8): e12399. doi:10.1371/journal.pone.0012399
Competing Interests:
The authors have declared that no competing interests exist.
Funding:
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. The funders had no role in study design, data collection and analysis,decision to publish, or preparation of the manuscript.
Source:
Jen Laloup
Public Library of Science (December 2010)
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