Nav: Home

Scientists reverse mechanism of fatty liver disease

June 13, 2017

Researchers have identified the mechanism which causes a build-up of fat in the liver in a disease affecting one in five in the UK -- and were able to reverse it in a mouse model.

People with Non-Alcoholic Fatty Liver Disease (NAFLD) develop excess fat in the liver even though they drink little or no alcohol. The condition can range from simple fatty liver to fibrosis and cirrhosis, and can ultimately lead to liver cancer.

A group of international researchers publishing today in the journal Nature Communications, report that senescent or old cells in the liver store excessive fat because mitochondria, the batteries of the cells, become damaged and cannot effectively use the fat as a source of fuel, resulting in its storage.

Reversing the process

Researchers from the Newcastle University Institute for Ageing, UK, in collaboration with researchers from the Mayo Clinic, USA, and the Erasmus Medical Centre, in the Netherlands, used pharmacological and genetic approaches to "kill-off" senescent cells from mice, to decrease the build-up of unwanted fat in the liver and restore liver function to normal.

Dr Diana Jurk from Newcastle University's Institute for Ageing, who leads the research team, said: "This is the first time that we have an effective therapy for fatty liver disease. Our discovery shows that by using this new method that can kill senescent cells, we may be able to make a significant impact in dealing with this very common life-threatening disease.

"While our approach worked in laboratory mice, we hope in the near future to be able to test these interventions in humans and potentially make a positive impact on people's lives."

Method

The team used two separate methods to eliminate senescent cells; firstly by using a genetically engineered mouse in which senescent, worn-out cells can be "killed-off" and secondly by a treatment with a combination of the drugs -- dasatinib and quercetin (D+Q) -- known to specifically kill senescent cells.

Both approaches were equally successful in reducing the build-up of fat in the liver caused by a high fat diet or ageing in mice.

Mikolaj Ogrodnik, PhD student within the Institute for Ageing and lead author on the paper, said: "We are witnessing a very exciting time in ageing research. Scientists have realised that senescent cells are the cause of many diseases and we now have a way to fight them off."

Dr Jurk adds: "As we age we accumulate cell damage and we have shown that these older cells are storing excess fat due to their inefficient mitochondria. What is exciting is that we have been able to reverse this damage in mice by removing these older, worn-out cells, which opens the door to a potential cure."

The work has been funded by the BBSRC and Newcastle University's Institute for Ageing.

The team are now intending to further their research by examining how the technique can be developed as a potential clinical treatment.
-end-
Reference: Cellular senescence drives age-dependent hepatic steatosis. Mikolaj Ogrodnik et al. Cellular senescence drives age-dependent hepatic steatosis. Nature Communications. Doi: 10.1038/ncomms15691

NAFLD
  • Non-Alcoholic Fatty Liver Disease is caused by a build-up of fat in the liver cells
  • NAFLD develops in four main stages:


1. simple fatty liver (steatosis) - a largely harmless build-up of fat in the liver cells that may only be diagnosed during tests carried out for another reason v2. non-alcoholic steatohepatitis (NASH) - a more serious form of NAFLD, where the liver has become inflamed; this is estimated to affect up to 5% of the UK population

3. fibrosis - where persistent inflammation causes scar tissue around the liver and nearby blood vessels, but the liver is still able to function normally

4. cirrhosis - the most severe stage, occurring after years of inflammation, where the liver shrinks and becomes scarred and lumpy; this damage is permanent and can lead to liver failure (where your liver stops working properly) and liver cancer
  • There aren't usually any symptoms of NAFLD in the early stages. You probably won't know you have it unless it's diagnosed during tests carried out for another reason.
  • Occasionally, people with NASH or fibrosis may experience: a dull or aching pain in the top right of the tummy (over the lower right side of the ribs), fatigue (extreme tiredness), unexplained weight loss, weakness


http://www.nhs.uk/conditions/fatty-liver-disease/pages/introduction.aspx

Once the paper is published electronically, it can be viewed at: http://dx.doi.org/10.1038/NCOMMS15691

Newcastle University

Related Mitochondria Articles:

Unexpected insights into the dynamic structure of mitochondria
As power plants and energy stores, mitochondria are essential components of almost all cells in plants, fungi and animals.
Mitochondria are the 'canary in the coal mine' for cellular stress
Mitochondria, tiny structures present in most cells, are known for their energy-generating machinery.
Master regulator in mitochondria is critical for muscle function and repair
New study identifies how loss of mitochondrial protein MICU1 disrupts calcium balance and causes muscle atrophy and weakness.
Oxygen deficiency rewires mitochondria
Researchers slow the growth of pancreatic tumor cells.
Self-cannibalizing mitochondria may set the stage for ALS development
Northwestern Medicine scientists have discovered a new phenomenon in the brain that could explain the development of early stages of neurodegeneration that is seen in diseases such as ALS, which affects voluntary muscle movement such as walking and talking.  The discovery was so novel, the scientists needed to coin a new term to describe it: mitoautophagy, a collection of self-destructive mitochondria in diseased upper motor neurons of the brain that begin to disintegrate from within at a very early age.
Uncovering the presynaptic distribution and profile of mitochondria
In a recent study published in the Journal of Neuroscience, scientists from the MPFI and the University of Iowa CCOM have provided unprecedented insight into the presynaptic distribution and profile of mitochondria in the developing and mature calyx of Held.
Temple researchers identify new target regulating mitochondria during stress
Like an emergency response team that is called into action to save lives, stress response proteins in the heart are activated during a heart attack to help prevent cell death.
Runaway mitochondria cause telomere damage in cells
Targeted damage to mitochondria produces a 'Chernobyl effect' inside cells, pelting the nucleus with harmful reactive oxygen species and causing chromosomal damage.
Interplay between mitochondria and nucleus may have implications for new treatment
Mitochondria, the 'batteries' that produce our energy, interact with the cell's nucleus in subtle ways previously unseen in humans, according to research published today in the journal Science.
Dissolving protein traffic jam at the entrance of mitochondria
Researchers from Freiburg discovered a novel mechanism that ensures obstacle-free protein traffic into the powerhouse of the cell.
More Mitochondria News and Mitochondria Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Listen Again: Reinvention
Change is hard, but it's also an opportunity to discover and reimagine what you thought you knew. From our economy, to music, to even ourselves–this hour TED speakers explore the power of reinvention. Guests include OK Go lead singer Damian Kulash Jr., former college gymnastics coach Valorie Kondos Field, Stockton Mayor Michael Tubbs, and entrepreneur Nick Hanauer.
Now Playing: Science for the People

#562 Superbug to Bedside
By now we're all good and scared about antibiotic resistance, one of the many things coming to get us all. But there's good news, sort of. News antibiotics are coming out! How do they get tested? What does that kind of a trial look like and how does it happen? Host Bethany Brookeshire talks with Matt McCarthy, author of "Superbugs: The Race to Stop an Epidemic", about the ins and outs of testing a new antibiotic in the hospital.
Now Playing: Radiolab

Dispatch 6: Strange Times
Covid has disrupted the most basic routines of our days and nights. But in the middle of a conversation about how to fight the virus, we find a place impervious to the stalled plans and frenetic demands of the outside world. It's a very different kind of front line, where urgent work means moving slow, and time is marked out in tiny pre-planned steps. Then, on a walk through the woods, we consider how the tempo of our lives affects our minds and discover how the beats of biology shape our bodies. This episode was produced with help from Molly Webster and Tracie Hunte. Support Radiolab today at Radiolab.org/donate.