non-alcoholic fatty liver disease Archives - Sanford Burnham Prebys

Tag: non-alcoholic fatty liver disease

Institute News

Fishman Fund Fellowship awarded to Cynthia Lebeaupin for liver cancer research

AuthorMiles Martin
Date

June 8, 2022

Cynthia Lebeaupin, PhD

Cynthia Lebeaupin, PhD was recently awarded the 2022 Fishman Fund Fellowship, a postdoctoral award unique to Sanford Burnham Prebys.

The award provides a boosted stipend to exceptional postdocs from the Institute who have a demonstrated research track record and whose work shows significant potential for future breakthroughs.

“It’s an honor to have been selected for such a prestigious award from the Institute, says Lebeaupin, who works in the lab of Randal J. Kaufman, PhD “The resources and people at Sanford Burnham Prebys are incredible and I’m happy to be able to continue my research here.” 

Sanford Burnham Prebys introduced the Fishman Fund Awards in 2001 to honor of the Institute’s founders, Dr. William and Lillian Fishman. The fund was established by Reena Horowitz and the late Mary Bradley, longtime supporters of the Institute.

“The Fishmans created an Institute that fosters a collaborative, inspirational atmosphere for postdoc students,” said Horowitz at the 2021 Fishman Fund Awards. “The Fishmans understood that support for new science is a brilliant research investment.”

Lebeaupin has been at the Institute since 2018, and this is not her first honor from the Fishman Fund. In 2021, she was awarded a Fishman Fund Career Development Award, a smaller prize offered to several postdocs each year. She also completed an internship at the Institute’s former Lake Nona campus in 2014.

“I’ve had an affinity for Sanford Burnham Prebys for a long time,” says Lebeaupin. “I knew once I met Dr. Kaufman and everybody on campus that this was the best place to complete my postdoc.”

Lebeaupin’s research focuses on a growing and pressing problem in medicine – liver cancer. One of the major risk factors for developing liver cancer is fat accumulation in the liver, known as fatty liver disease. Increases in obesity rates over the last several decades have led to a dramatic increase in fatty liver disease.

Fatty liver disease is increasing at an alarming rate, and unfortunately, it’s here to stay,” says Lebeaupin. “My research is figuring out how fatty liver disease progresses to liver cancer, so we can use this knowledge to help prevent it.” 

In particular, Lebeaupin is working on exploring how cells respond to fatty liver disease over time. She discovered that a molecule that helps liver cells protect themselves from short-term stress can promote cancer in the long-term. She has now moved into studying the system in human tissues.

“This research is exciting because we aim to translate our discoveries from the bench to the bedside,” says Lebeaupin. “What I hope to do in the future is use new technologies on liver samples from patients so we can identify what’s actually going on in liver diseases.”

Institute News

How cholesterol-lowering drugs ameliorate fatty liver disease

AuthorJessica Moore
Date

October 27, 2016

Fatty liver tissue (trichrome stain)

Nonalcoholic fatty liver disease (NAFLD) is quietly becoming an epidemic alongside obesity—up to 20% of people in Western countries have it. Though NAFLD, the mildest of a spectrum of liver diseases characterized by excess fat in liver cells, has no symptoms at first, it increases risk for liver cancer and can worsen to nonalcoholic steatohepatitis (NASH) or even liver failure.

There are no specific treatments for NAFLD, but cholesterol-lowering drugs called statins appear to slow its progression to more serious liver inflammation and fibrosis/scarring, characteristics of NASH. However, they haven’t been widely adopted, in part because of concerns about statins’ potential liver toxicity, though recent analyses suggest that severe toxicity is rare.

Now, a study co-led by Timothy Osborne, PhD, professor and director of the Integrative Metabolism Program, and published in Scientific Reports, outlines the molecular pathway through which statins break down fat stores in the liver.

“We show directly that these drugs reduce the amount of fat molecules and cholesterol in the liver in an animal model of NAFLD,” said Osborne. “Our results provide support for using statins to treat NAFLD itself, even if patients’ serum cholesterol isn’t dangerously high.”

The experiments were initiated by Young-Kyo Seo, PhD, now a professor at the Ulsan National Institute of Science and Technology, while he was a postdoc in Osborne’s laboratory. The study was based on previous work that found statins activate a protein called SREBP-2, a transcription factor that activates genes to regulate cholesterol balance.

To figure out how statins work on liver cells, the team searched SREBP-2’s target genes for enzymes that break down fat molecules and found PNPLA8, which splits certain fat molecules into pieces that regulate cell signaling. Further experiments showed that PNPLA8 helps liver cells break down stored fat molecules.

The new study provides some hints as to PNPLA8’s mechanism. Statins are known to enhance a cellular recycling process called autophagy, which breaks down cell parts—such as lipid droplets, the site of fat storage—for energy and re-use. The new results suggest that this may depend on PNPLA8’s ability to target the autophagy machinery directly to lipid droplets.

“This is the first time PNPLA8 has been implicated in freeing fat from liver cells,” Osborne commented. “Looking in more detail at how it mobilizes fat stores will give us an idea of whether it might be a good drug target.”

Institute News

Novel model for cardiomyopathy paves the way for new therapies

Authorsgammon
Date

May 29, 2015

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A new fruit fly model that captures key metabolic defects associated with cardiomyopathy could translate into more-effective treatments for this potentially deadly heart condition, according to a study conducted by researchers at Sanford-Burnham and the Universidad Autónoma de Madrid in Spain. The findings, published April 9 in Human Molecular Genetics, could also have broader clinical implications for human metabolic diseases affecting other organ systems such as the liver and skeletal muscle. Continue reading “Novel model for cardiomyopathy paves the way for new therapies”

Institute News

Ketogenesis prevents fatty liver disease

Authorsgammon
Date

January 12, 2015

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A new study, published in the Journal of Clinical Investigation, suggests that ketogenesis may prevent non-alcoholic fatty liver disease (NAFLD). NAFLD is term used to describe the accumulation of fat in the liver of people who drink little or no alcohol. It affects approximately one billion individuals worldwide, has become a leading cause of cirrhosis, and increases the risk of cardiovascular disease, including heart attacks and stroke. Continue reading “Ketogenesis prevents fatty liver disease”