PRESS-NEWS.org - Press Release Distribution
PRESS RELEASES DISTRIBUTION

New potential therapy for fatty liver disease

In a subset of patients with partial lipodystrophy and/or NASH, the hormone leptin can be leveraged as a therapeutic agent to move fat out of the liver

2021-06-07
(Press-News.org) In those with fatty liver disease, a person's fat goes to their liver instead of their fat tissue, either because of an absence of fat depots, which is seen in the rare genetic disease lipodystrophy, or because the depots are too full, which is seen in people with obesity.

One third of these people will go on to develop nonalcoholic steatohepatitis, or NASH - an advanced form of fatty liver disease brought on by progressive inflammation and scarring in the organ.

In 2002, Michigan Medicine endocrinologist Elif Oral, M.D., who had just moved from the National Institutes of Health at the time, published her discovery that patients with severe lipodystrophy lack leptin, a hormone that helps curb appetite and control weight gain. When given leptin as a supplement, the patient's serious metabolic abnormalities like NASH improved substantially.

Oral set out to U-M to further study the role of leptin, now in more common forms of NASH. Almost two decades later, her research team found that whether from a leptin deficiency or the presence of partial lipodystrophy, patients with NASH and relatively low leptin levels can mobilize the extra fat in their liver, out of their liver, and help reverse their condition by undergoing leptin therapy.

"Familial partial lipodystrophy often accompanies NASH. It's a rare, genetic condition where patients have a lack of fat in their extremities but remain fat in their upper body," Oral explained. "I wanted to test the effect of leptin in both those with this rare condition and those that just present with NASH to see if there would be a difference in therapeutic outcomes."

This work, which is the first of its kind in humans and compiles research from three different studies, showed that leptin is an important signal in regulating fat deposition in the liver, and reversing fat deposition and its subsequent NASH.

During the lifetime of the study, the manufacturer of leptin changed several times, posing substantial bureaucratic obstacles for the research team to overcome.

"I could've moved on to something easier to study, but I wanted to see this through. This is my life's work," Oral said. "I'm grateful for all of my collaborators and co-authors for sticking with me through it all."

Outlined in Med: Cell Press, Oral and her team conducted two open-label trials studying nine male patients with NASH and relatively low leptin levels (less than 9 ng/ml) and 23 patients with both partial lipodystrophy and NASH. Both groups received leptin therapy in the form of metreleptin for one year.

The trials consisted of male patients because Oral found that 35-40% of the men that had leptin levels measured had levels less than the twenty-fifth percentile of their body weight, making them ideal study candidates.

"Not all NASH is created equal. There's a vast distribution of leptin levels in this patient population," Oral said. "High levels of leptin, seen in obesity, can actually be causative of NASH so it was important to carefully select trial participants for low levels."

After blind, paired liver biopsies, both groups were found to have reduced fat in the liver and lower NASH scores after 12 months of leptin therapy. The patients also had improved insulin sensitivity and body weight.

The findings are only applicable to leptin, but Oral thinks other molecules or treatments that activate leptin in the body could be of focus in future studies in an attempt to widen the therapeutic window for these patients.

After obesity is established, there's little gain by giving someone leptin. However, a patient in the early overweight state may get value from undergoing leptin therapy, inspiring the research team to study leptin as a preventive weight control option in those at risk of crossing the obesity threshold and developing more fat in the liver.

"Although these results were encouraging, this justifies a larger trial," Oral said. "But there's no approved treatments for NASH of any form, so to have a therapeutic that can help at least a fraction of these patients is exciting."

INFORMATION:

This study was funded by the National Institutes of Health, grant R03 DK074488 and R01 DK088114.

Paper cited: "Metreleptin therapy for nonalcoholic steatohepatitis: Open-label therapy interventions in two different clinical settings," Med: Cell Press. DOI: 10.1016/j.medj.2021.04.001



ELSE PRESS RELEASES FROM THIS DATE:

Feedback on cafeteria purchases helps employees make healthier food choices

2021-06-07
BOSTON - Automated emails and letters that provide personalized feedback related to cafeteria purchases at work may help employees make healthier food choices. That's the conclusion of a new study that was led by investigators at Massachusetts General Hospital (MGH) and is published in END ...

RUDN University chemists created anti-hantavirus drugs 5 times more efficient than existing drugs

RUDN University chemists created anti-hantavirus drugs 5 times more efficient than existing drugs
2021-06-07
RUDN University chemists and their colleagues from Novosibirsk State University, Novosibirsk Institute of Organic Chemistry and The State Research Center of Virology and Biotechnology VECTOR have obtained a new class of compounds that inhibit the replication of the deadly Hantaan virus that affects blood vessels and internal organs of humans. The resulting substances were 5 times more effective than existing antiviral drugs. The results have been published Bioorganic & Medicinal Chemistry Letters. The Hantaan virus causes acute haemorrhagic fever with renal syndrome (HFRS). The disease ...

Space travel weakens our immune systems: Now scientists may know why

2021-06-07
Microgravity in space perturbs human physiology and is detrimental for astronaut health, a fact first realized during early Apollo missions when astronauts experienced inner ear disturbances, heart arrhythmia, low blood pressure, dehydration, and loss of calcium from their bones after their missions. One of the most striking observations from Apollo missions was that just over half of astronauts became sick with colds or other infections within a week of returning to Earth. Some astronauts have even experienced re-activation of dormant viruses, such as the chickenpox virus. These findings stimulated studies on the effects of weak gravity, or ...

Drop in convalescent plasma use at US hospitals linked to higher COVID-19 mortality rate

2021-06-07
A new study from researchers at Johns Hopkins Bloomberg School of Public Health and colleagues suggests a slowdown in the use of convalescent plasma to treat hospitalized COVID-19 patients led to a higher COVID-19 mortality during a critical period during this past winter's surge. U.S. hospitals began treating COVID-19 patients with convalescent plasma therapy--which uses antibody-rich blood from recovered COVID-19 patients--in the summer of 2020 when doctors were looking to identify treatments for the emerging disease. By the spring of 2021, doctors in the United States had treated over 500,000 COVID-19 patients with convalescent plasma. The use ...

Mice fathers pass down stress responses to offspring via sperm

Mice fathers pass down stress responses to offspring via sperm
2021-06-07
Male mice more susceptible to stress can pass down their behaviors to offspring via changes in their sperm's genetic code, according to new research published in JNeurosci. Stressful experiences alter gene expression, which parents can pass down to their offspring. But it was unclear if sperm itself transmits this information, or if behavioral cues between the parents play a larger role. Cunningham et al. tracked the stress response of male mice after ten days of chronic stress and sorted them into resilient and susceptible groups, based on the severity of their response. The offspring of resilient and control mice showed decreased stress behaviors ...

Health benefits of low protein-high carbohydrate diets depend on carb type

Health benefits of low protein-high carbohydrate diets depend on carb type
2021-06-07
Researchers at the University of Sydney's Charles Perkins Centre conducted the largest ever study of nutrient interactions by examining the health of mice on 33 different diets containing various combinations of protein to carbs, and different sources of carbohydrate. They found that a low-protein (10% of dietary energy), high-carbohydrate (70%) diet produced either the healthiest or unhealthiest metabolic outcomes of all 33 diets, depending on the kind of carbs. When carbs were made up mainly of resistant starch, a form of starch that is resistant to digestion and is fermented by bacteria in the gut, the low protein diet was the healthiest of all diets. When the ...

Gender bias is real for women in family-owned businesses

Gender bias is real for women in family-owned businesses
2021-06-07
A study examining gender bias and family-owned businesses found daughters were rarely encouraged nor received support to pursue entrepreneurship education while sons mostly did. Professors James Combs, Peter Jaskiewicz, and Sabine Raul from the Telfer School of Management uncovered new insights about how gender bias - the preference of a gender over the other - affects the succession strategy in multi-generational family firms. Their findings are published in the Journal of Small Business Management. When nurturing the next generation, entrepreneurial families often prepare their daughters and sons differently for their careers. The researchers noticed a common pattern in the stories shared by the next generation: Sons are often nurtured to ...

Stream of stars extends thousands of light-years across the Milky Way

2021-06-07
It's hard to see more than a handful of stars from Princeton University, because the lights from New York City, Princeton and Philadelphia prevent our sky from ever getting pitch black, but stargazers who get into more rural areas can see hundreds of naked-eye stars -- and a few smudgy objects, too. The biggest smudge is the Milky Way itself, the billions of stars that make up our spiral galaxy, which we see edge-on. The smaller smudges don't mean that you need glasses, but that you're seeing tightly packed groups of stars. One of the best-known of these "clouds" or "clusters" -- groups of stars that travel together -- is the Pleiades, also known as the Seven Sisters. Clusters are stellar nurseries where thousands of stars are born from clouds of gas and dust and then ...

A quantum step to a heat switch with no moving parts

2021-06-07
COLUMBUS, Ohio - Researchers have discovered a new electronic property at the frontier between the thermal and quantum sciences in a specially engineered metal alloy - and in the process identified a promising material for future devices that could turn heat on and off with the application of a magnetic "switch." In this material, electrons, which have a mass in vacuum and in most other materials, move like massless photons or light - an unexpected behavior, but a phenomenon theoretically predicted to exist here. The alloy was engineered with the elements bismuth and antimony at precise ranges based ...

CO2 sensors in two urban areas registered big drop in emissions during COVID-19 pandemic

2021-06-07
Carbon dioxide emissions in Los Angeles fell 33% in April of 2020 compared with previous years, as roads emptied and economic activity slowed due to the COVID-19 pandemic, according to a new study in Geophysical Research Letters. In the Washington, D.C./Baltimore region, emissions of carbon dioxide, or CO2, dropped by 34% during the same period. The study was led by scientists at NASA's Jet Propulsion Laboratory (JPL), the National Institute of Standards and Technology (NIST) and the University of Notre Dame. While the emissions reductions are significant, the method that scientists used to measure them may have the greater long-term impact. In both locations, scientists had previously ...

LAST 30 PRESS RELEASES:

Scientists unlock secrets behind flowering of the king of fruits

Texas A&M researchers illuminate the mysteries of icy ocean worlds

Prosthetic material could help reduce infections from intravenous catheters

Can the heart heal itself? New study says it can

Microscopic discovery in cancer cells could have a big impact

Rice researchers take ‘significant leap forward’ with quantum simulation of molecular electron transfer

Breakthrough new material brings affordable, sustainable future within grasp

How everyday activities inside your home can generate energy

Inequality weakens local governance and public satisfaction, study finds

Uncovering key molecular factors behind malaria’s deadliest strain

UC Davis researchers help decode the cause of aggressive breast cancer in women of color

Researchers discovered replication hubs for human norovirus

SNU researchers develop the world’s most sensitive flexible strain sensor

Tiny, wireless antennas use light to monitor cellular communication

Neutrality has played a pivotal, but under-examined, role in international relations, new research shows

Study reveals right whales live 130 years — or more

Researchers reveal how human eyelashes promote water drainage

Pollinators most vulnerable to rising global temperatures are flies, study shows

DFG to fund eight new research units

Modern AI systems have achieved Turing's vision, but not exactly how he hoped

Quantum walk computing unlocks new potential in quantum science and technology

Construction materials and household items are a part of a long-term carbon sink called the “technosphere”

First demonstration of quantum teleportation over busy Internet cables

Disparities and gaps in breast cancer screening for women ages 40 to 49

US tobacco 21 policies and potential mortality reductions by state

AI-driven approach reveals hidden hazards of chemical mixtures in rivers

Older age linked to increased complications after breast reconstruction

ESA and NASA satellites deliver first joint picture of Greenland Ice Sheet melting

Early detection model for pancreatic necrosis improves patient outcomes

Poor vascular health accelerates brain ageing

[Press-News.org] New potential therapy for fatty liver disease
In a subset of patients with partial lipodystrophy and/or NASH, the hormone leptin can be leveraged as a therapeutic agent to move fat out of the liver