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 José 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.
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Controlling electronic current is essential to modern electronics, as data and signals are transferred by streams of electrons which are controlled at high speed. Demands on transmission speeds are also increasing as technology develops. Scientists from the Chair of Laser Physics and the Chair of Applied Physics at Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU) have succeeded in switching on a current with a desired direction in graphene using a single laser pulse within a femtosecond ¬¬ – a femtosecond corresponds to the millionth part of a billionth of a second. This is more than a thousand times faster compared to the most efficient transistors today.
Graphene is up to the job
At the productronica trade fair in Munich this November, the Fraunhofer Institute for Laser Technology ILT will be presenting Laser-Based Tape-Automated Bonding, LaserTAB for short. The experts from Aachen will be demonstrating how new battery cells and power electronics can be micro-welded more efficiently and precisely than ever before thanks to new optics and robot support.
Fraunhofer ILT from Aachen relies on a clever combination of robotics and a laser scanner with new optics as well as process monitoring, which it has developed...
Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.
A warming planet
Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.
The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...
Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...
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