UCI study reveals new mechanism for estrogen suppression of liver lipid synthesis

Findings point to potential new treatment approaches for liver diseases

2013-05-24

(Press-News.org) By discovering the new mechanism by which estrogen suppresses lipid synthesis in the liver, UC Irvine endocrinologists have revealed a potential new approach toward treating certain liver diseases.

With this finding, Dr. Ellis Levin and colleagues believe they are changing long-held views in the field. Study results appear in the May 21 issue of the journal Science Signaling.

"The dogma in the steroid receptor field for 50 years has been that only receptors located in the nucleus respond to steroid hormones by regulating genes that produce the developmental, functional and pathological effects of steroid hormones," said Levin, Professor of Medicine, biological chemistry and pharmacology, and Chief of endocrinology, diabetes and metabolism at UC Irvine and the VA Long Beach Healthcare System.

"In our study, we show that an estrogenic receptor compound acting at the cell membrane-based estrogen receptor alpha in the liver of transgenic and wild type mice suppresses all lipid synthesis. This includes cholesterol, triglycerides and fatty acids."

Levin said this occurs through AMP kinase signaling, which inhibits the processing of the key transcription factor for many lipid-synthesis pathways genes. This causes the transcription factor to be retained in cytoplasm and prevents lipid synthesis gene expression.

"This action occurs without any participation of the nuclear receptor pool," he added. "Thus, the membrane ER-alpha can regulate genes that produce a metabolic phenotype entirely unrelated to the nuclear receptor contributing."

Estrogen plays a role in liver functions, and may be a deterrent to liver cancer, as men get this type of cancer at a rate of four-to-six times more than women and animals models of this cancer show clear suppression by estrogen. The hormone also helps suppress the development of fatty liver, which can lead to liver damage and failure, and inflammatory liver disease that result from chronic hepatitis. Levin said that he and his colleagues are now testing compounds that target the membrane estrogen receptor in transgenic mice to see the impact for such diseases.

"We're re-thinking the whole idea of hormone replacement of estrogen by exploring ways to boost estrogen receptor action selectively in a positive way," he said. "This could include targeting one form of the receptor, or receptors at one location in cells but not all estrogen receptors."

Last month, Levin was honored with the 2013 Solomon A. Berson Distinguished Researcher Award and Lectureship from the American Physiological Society, Endocrinology Division. The award is in recognition of Levin's work on estrogen receptors outside the nucleus that mediates important functions of this steroid in breast cancer and the cardiovascular system, and is applicable to many other steroid receptors, including progesterone and androgen receptors in breast and prostate cancer, respectively.

### Ali Pedram and Fiona O'Mahony with UC Irvine, Mahnaz Razandi with the VA Long Beach Healthcare System, and Brian J. Harvey and Harry Harvey with the Royal College of Surgeons in Dublin, Ireland, contributed to the study, which was supported by grants from National Institutes of Health (CA-100366) and the Department of Veterans Affairs Merit Review Program (ERL). O'Mahony, who is also affiliated with the VA Long Beach Healthcare System was co-funded by Marie Curie Actions, the Irish Higher Education Authority Programme for Third Level Institutions Cycle 4, and the Italian National Research Council.

ELSE PRESS RELEASES FROM THIS DATE:

Understanding job committment may lead to better correctional employees

2013-05-24

DETROIT — Commitment to the job by correctional staff members cannot be bought but must be earned by an organization, a Wayne State University researcher believes. A study by Eric Lambert, Ph.D., professor and chair of criminal justice in the College of Liberal Arts and Sciences, describes three types of commitment and the effects of three organizational concepts on them, based on a survey of 450 staff members at a maximum-security correctional institution in Michigan. "Loyalty, Love, and Investments: The Impact of Job Outcomes on the Organizational Commitment of Correctional ...

Scientists offer first definitive proof of bacteria-feeding behavior in green algae

2013-05-24

A team of researchers has captured images of green alga consuming bacteria, offering a glimpse at how early organisms dating back more than 1 billion years may have acquired free-living photosynthetic cells. This acquisition is thought to have been a critical first step in the evolution of photosynthetic algae and land plants, which, in turn, contributed to the increase in oxygen levels in Earth's atmosphere and ocean and provided one of the conditions necessary for animal evolution. In a paper that appears in the June 17 issue of Current Biology and is available online ...

Death rates decline for advanced heart failure patients, but outcomes are still not ideal

2013-05-24

UCLA researchers examining outcomes for advanced heart-failure patients over the past two decades have found that, coinciding with the increased availability and use of new therapies, overall mortality has decreased and sudden cardiac death, caused by the rapid onset of severe abnormal heart rhythms, has declined. However, the team found that even today, with these significant improvements, one-third of patients don't survive more than three years after being diagnosed with advanced disease. Heart failure is increasingly common, affecting close to 6 million individuals ...

Syracuse University professor argues Earth's mantle affects long-term sea-level rise estimates

2013-05-24

From Virginia to Florida, there is a prehistoric shoreline that, in some parts, rests more than 280 feet above modern sea level. The shoreline was carved by waves more than 3 million years ago—possible evidence of a once higher sea level, triggered by ice-sheet melting. But new findings by a team of researchers, including Robert Moucha, assistant professor of Earth Sciences in Syracuse University's College of Arts and Sciences, reveal that the shoreline has been uplifted by more than 210 feet, meaning less ice melted than expected. Equally compelling is the fact that ...

H7N9 animal model looks at transmission of H7N9 influenza virus

2013-05-24

Toronto – May 23, 2013 – Embargoed until 2:00 PM – An international team of scientists has proved that the H7N9 influenza virus is efficiently transmitted when animals are in close contact -- defined in the study as touching, coughing and the exchange of bodily fluids. "This study was designed to give us clues about the transmission of H7N9 which has affected some humans in China," said David Kelvin, PhD, a senior scientist at the Toronto General Research Institute and Professor at the University of Toronto. "The animals used in the study had very mild clinical symptoms ...

University of Illinois biophysicists measure mechanism that determines fate of living cells

2013-05-24

Cells in the human body do not function in isolation. Living cells rely on communication with their environment—neighboring cells and the surrounding matrix—to activate a wide range of cellular functions, including reproduction of new cells, differentiation of stem cells into distinct cell types, cell adhesion, and migration of white blood cells to fight bodily infections. This cellular communication occurs on the molecular level and it is reciprocal: a cell receives cues from and also transmits function-activating cues to its neighbors. The mechanics of this type of ...

UC Santa Barbara scientists discover cinnamon compounds' potential ability to prevent Alzheimer's

2013-05-24

Cinnamon: Can the red-brown spice with the unmistakable fragrance and variety of uses offer an important benefit? The common baking spice might hold the key to delaying the onset of –– or warding off –– the effects of Alzheimer's disease. That is, according to Roshni George and Donald Graves, scientists at UC Santa Barbara. The results of their study, "Interaction of Cinnamaldehyde and Epicatechin with Tau: Implications of Beneficial Effects in Modulating Alzheimer's Disease Pathogenesis," appears in the online early edition of the Journal of Alzheimer's Disease, and ...

Ferrets, pigs susceptible to H7N9 avian influenza virus

2013-05-24

Chinese and U.S. scientists have used virus isolated from a person who died from H7N9 avian influenza infection to determine whether the virus could infect and be transmitted between ferrets. Ferrets are often used as a mammalian model in influenza research, and efficient transmission of influenza virus between ferrets can provide clues as to how well the same process might occur in people. The research was supported, in part, by the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health. The researchers dropped H7N9 virus into ...

Reforestation study shows trade-offs between water, carbon and timber

2013-05-24

More than 13,000 ships per year, carrying more than 284 million tons of cargo, transit the Panama Canal each year, generating roughly $1.8 billion dollars in toll fees for the Panama Canal Authority. Each time a ship passes through, more than 55 million gallons of water are used from Gatun Lake, which is also a source of water for the 2 million people living in the isthmus. However, the advent of very large "super" cargo ships, now more than 20 percent of the ships at sea, has demanded change. The Panama Canal is being expanded to create channels and locks three times ...

New filtration material could make petroleum refining cheaper, more efficient

2013-05-24

A newly synthesized material might provide a dramatically improved method for separating the highest-octane components of gasoline. Measurements at the National Institute of Standards and Technology (NIST) have clarified* why. The research team, which included scientists from NIST and several other universities, has published its findings in the journal Science.* Created in the laboratory of Jeffrey Long, professor of chemistry at the University of California, Berkeley, the material is a metal-organic framework, or MOF, which can be imagined as a sponge with microscopic ...

UCI study reveals new mechanism for estrogen suppression of liver lipid synthesis

ELSE PRESS RELEASES FROM THIS DATE:

LAST 30 PRESS RELEASES: