- ROCHESTER, Minn. -- Obesity
is the number one cause of chronic liver disease in the United States.
Mayo Clinic researchers have discovered the mechanism that causes liver
damage in many obese children and adults: excess fatty acids cause a protein
reaction that kills liver cells, causing scarring and liver damage.
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- Known as Non-Alcoholic Fatty Liver Disease - NAFLD -
the condition was first identified and named by a Mayo Clinic research
team in 1980. It affects up to a quarter of the population in western countries.
The latest Mayo Clinic discovery on NAFLD appears in today's version of
the journal Hepatology online.
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- "As a pediatrician, I feel we are dealing with a
big epidemic - NAFLD is certainly surpassing Hepatitis C, in terms of potential
damage to the liver," says Ariel Feldstein, M.D., Mayo Clinic pediatric
gastroenterologist and principal investigator. "NAFLD is a growing
worldwide problem related to affluence and the diet and lifestyle associated
with it. It's as true in the U.S. as it is in Europe, Japan, and my native
country Argentina." See how NAFLD occurs here.
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- Early signs of NAFLD consist of accumulation of fat in
the liver, which can be found in almost two-thirds of obese people. Another
indication is inflammation of the liver, sometimes with scarring. While
simple fatty liver is usually a benign condition, about 10 percent of individuals
can develop other liver abnormalities including inflammation and scarring
that can lead to impaired function in a condition known as Nonalcoholic
Steatohepatitis, or NASH. Both NAFLD and NASH are strongly associated with
other components of the metabolic syndrome including diabetes, elevated
cholesterol and triglyceride levels, and hypertension.
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- Significance of the Mayo Clinic Research
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- The discovery of how excess fatty acids poison livers
is important because currently there is no treatment for obesity-associated
liver disease. Knowing the cellular mechanisms behind NAFLD is the necessary
first step to developing treatments for it. And while most cases of NAFLD
do not progress to cirrhosis or require a liver transplant, physicians
are nonetheless worried that this could change because they are seeing
more symptoms of pediatric NAFLD earlier.
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- "Every week I have several patients in which the
mean age is about 12 that come with symptoms of liver disease-and that's
very young for this to be happening," says Dr. Feldstein. "Perhaps
1 in 10 of my patients has signs of liver disease, and that group can be
thought of as the first step toward NASH: nonalcoholic steatohepatitis."
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- Other symptoms include an enlarged liver or minor elevation
of the liver enzyme in tests. Fatty liver disease can be suspected based
on ultrasound or computerized tomography (CT) scan, but the diagnosis must
be confirmed by liver biopsy.
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- The Experiment and Its Findings
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- By studying livers of both obese and lean mice, as well
as liver samples from obese and lean human patients, the Mayo Clinic researchers
discovered key points about how NAFLD works. The process starts when there's
so much dietary fat in the blood that it can no longer be contained in
the usual storage places, such as fat cells. When this happens, the fatty
acids are "free," roving around space inside cells known as cytosol.These
freely circulating fatty acids inside the liver cells' cytosol start the
chain of events that the Mayo Clinic researchers discovered.
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- Understanding these processes gives researchers a basis
for designing treatments to interrupt the chain of events, and thus, shut
down injurious cellular processes. This could lead one day to new drugs
for NAFLD. Drug-development approaches are important because the only treatment
for early-stage NAFLD now is the same as that prescribed for the other
symptoms of metabolic syndrome, such as insulin resistance, high blood
pressure, high blood fats, and these measures- eat less and exercise more
to lose weight- are difficult for certain patients to do.
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- In addition to Dr. Feldstein, the Mayo Clinic research
paper was authored by Nathan W. Werneburg, Ali Canbay, M.D.; Maria Eugenia
Guicciardi, Ph.D.; Steven F. Bronk, Robert Rydzewski, Laurence J. Burgart,
M.D., and Gregory Gores, M.D., in whose laboratory the investigation was
conducted. The work was supported by a grant from the National Institutes
of Health to Dr. Gores, the American Gastroenterological Association Transition
Award to Dr. Feldstein, and the Mayo Foundation.
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