Cholesterol,
glutathion en leverproblemen.*
Cholesterol speelt volgens een nieuw onderzoek een belangrijke rol bij het ontstaan van en voortgang van een “vette lever”. Een vette lever leidt op termijn tot onherstelbare leverschade. Opeenhoping van cholesterol in de lever doet de waarde van de krachtige lichaamsantioxidant glutathion flink dalen. Alleen cholesterol en niet andere vorm van vet in de lever doen de leverziekte verergeren. Het is dus belangrijk ervoor te zorgen om het cholesterol in het lichaam laag te houden en een aanvullend glutathion verhogend supplement te nemen.
Cholesterol
Implicated In Progression Of Fatty Liver Disease
Cholesterol
may play an important role in the progression of fatty liver to an advanced
stage of disease that can lead to permanent liver damage, according to a report
in the September, 2006 issue of the journal Cell Metabolism, published by Cell
Press. The findings suggest that low-cholesterol diets or cholesterol-lowering
drugs might offer a useful therapy for the rising epidemic of fatty liver
disease.
The researchers found in mice that accumulation of cholesterol in the liver
depletes a powerful antioxidant. The depleted cells are left sensitive to
inflammatory factors that cause damage to the liver, they found. The buildup of
other forms of fat in the liver, including free fatty acids and triglycerides,
were insufficient to spark the events leading to worsening disease.
The findings suggest a key role for the type, as opposed to the amount, of fat
in susceptibility to the liver condition known as nonalcoholic steatohepatitis (NASH),
said Jose Fernandez-Checa and Carmen García-Ruiz of Consejo Superior de
Investigaciones Científicas (CSIC) in Barcelona.
"To avoid the progression of liver disease, it may be important to eat less
and be more conscious of the lipid content of the diet, particularly
cholesterol," Fernandez-Checa said. Supplements that boost levels of
glutathione--the antioxidant that becomes depleted in animals whose livers
accumulate cholesterol--might also be beneficial, he added.
"These data also support a potential therapeutic role of statins in NASH
development," he added. Statins are a class of drugs used to lower
cholesterol in those at risk of cardiovascular disease.
Characterized by fat accumulation, inflammation, and liver damage, NASH affects
2%-5% percent of Americans. An additional 10%-20% percent of Americans have fat
in their liver, but no inflammation or liver damage. Both conditions are
becoming more prevalent, possibly due to the rise of obesity.
The accumulation of lipids in the liver cells, mostly in the form of fatty acids
and triglycerides, had been considered the first step in the development of
fatty liver disease, the researchers said. However, disease progression usually
does not occur in the absence of a second hit that promotes oxidative stress,
inflammation, cell death, and fibrosis.
In the current study, the researchers examined the connection between fat type
and liver disease progression in mice with high levels of particular lipids in
the liver as a result of their diet or genetic modifications that left them
obese or unable to handle cholesterol properly.
In every case, mice with high levels of cholesterol in their livers became
increasingly susceptible to two inflammatory factors known as cytokines, they
found. The cholesterol accumulated specifically in the cellular powerhouses
known as mitochondria, where it caused a drop in glutathione. Treatments that
selectively depleted liver cells of glutathione produced symptoms that mirrored
the effects of high liver cholesterol, they reported.
In obese mice, treatment with the cholesterol-lowering drug Atorvastatin
prevented the cholesterol increase in mitochondria and restored antioxidant
levels, offering protection from liver damage.
The new findings represent some of the first evidence for a role of cholesterol
in delivering the "second hit" that leads to full-blown NASH,
Fernandez-Checa said.
Earlier studies that found a poor correlation between blood cholesterol levels
and fatty liver disease had led to some doubt about cholesterol's role, he added.
Cholesterol metabolism is a complicated process, however, such that blood levels
might not always reflect the amount of cholesterol in the liver, he said.
###
The researchers include Montserrat Marí, Francisco Caballero, Anna Colell,
Albert Morales, Juan Caballeria, Anna Fernandez, Carlos Enrich, Jose C.
Fernandez-Checa, and Carmen García-Ruiz of the Universitat de Barcelona,
Instituto Investigaciones Biomédicas August Pi i Sunyer (IDIBAPS), Consejo
Superior de Investigaciones Científicas in Barcelona, Spain.
The work presented was
supported in part by the Research Center for Liver and Pancreatic Diseases, P50
AA 11999; and grant 1R21 AA014135-01, funded by the US National Institute on
Alcohol Abuse and Alcoholism; Plan Nacional de I+D grants SAF (2002-3564,
2003-04974, 2005-03923, 2005-03943); and Red Tematica de Investigacion
Cooperativa G03/015, Red de Centros C03/02 and FIS (04/1039, 03/0426, 02/3057
and 02/0339) grants supported by Instituto de Salud Carlos III, Spain.
Marí et al.: "Mitochondrial free cholesterol loading sensitizes to TNF-
and Fas-mediated steatohepatitis." Publishing in Cell Metabolism 4,
185-198, September 2006 DOI 10.1016/j.cmet.2006.07.006
Related Preview by Ginsberg et al.: "Is the slippery slope from steatosis
to steatohepatitis paved with triglyceride or cholesterol?"
Contact: Heidi Hardman
(Sept. 2006) (Opm. Kijk bij Specifiek advies hoe u hoge cholesterolwaarden kunt voorkomen of bestrijden en kijk bij ImmunoPro voor het beste supplement ter verhoging van glutathionwaarden in het lichaam.)