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Study Shows Component of Common Supplement May Alleviate Fatty Liver Disease, Improve Insulin Sensitivity

Researchers from Baylor College of Medicine, the Emery School of Medicine, and The Scripps Research Institute have found that a natural product increases sensitivity to insulin and reduces fatty liver in mice, suggesting it may be able to provide a treatment for prediabetic patients.

The study, which appears in the June 23, 2011 print edition of the journal Nature, focuses on a trace component of lecithin called DLPC (dilauroyl phosphatidylcholine). Lecithin, a major constituent of cell membranes, is found in foods including egg yolk, soybeans, grains, wheat germ, fish, legumes, yeast, and peanuts; it is also available in supplement form.

The new study found that, in mice, DLPC induced the production of bile acid enzymes, lowered fat in the liver, and dramatically improved insulin sensitivity.

"Their overall body weight was not changed," said David D. Moore, professor of molecular and cellular biology at Baylor College of Medicine. "But they had improved sensitivity to insulin (which helps keep glucose levels in check) and less fatty livers."

Fatty liver, which is associated with diabetes, high blood pressure, and cardiovascular disease, can lead to scarring of the liver and poor liver function. Insulin sensitivity is important for maintaining healthy levels of blood sugar, which helps prevent type 2 diabetes.

Clinical Trial Planned

The researchers first became interested in DLPC as a tool for studying the function of a receptor protein—liver receptor homolog-1 or LRH-1—that regulates the production of bile acids in the liver. The team then screened compounds to identify candidates that activated LRH-1 function, finding that DLPC enhanced LRH-1 activity in cells.

"Our lab at Scripps Florida has been developing assays to support discovery of synthetic inverse agonists of LRH1 as potential treatments as anti-cancer agents," said Patrick Griffin, chair of the Department of Molecular Therapeutics and director of the Translational Research Institute at Scripps Florida. "These same assays were used in our collaboration with David Moore's efforts demonstrating the natural product DLPC bound specifically to LRH1 and modulated the interaction with coactivator proteins."

While DLPC decreased fatty liver and lowered glucose levels in the blood in two kinds of mice that had resistance to insulin, DLPC had no effect in mice lacking LRH-1 in the liver, underlining the dependence on LRH-1 for these biological effects.

A pilot clinical study of DLPC for patients with prediabetes has been launched at Baylor in Waco, Texas; those who wish to enroll should contact Dr. Kerem Ozer at 713-798-7684.

In addition to Moore and Griffin, authors of the Nature article, "A nuclear-receptor-dependent phosphatidylcholine pathway with antidiabetic effects," include Jae Man Lee, Yoon Kwang Lee, and Jennifer L. Mamrosh of Baylor; Scott A. Busby of Scripps Florida; and Manish C. Pathak and Eric A. Ortlund of Emory. For more information, seehttp://www.nature.com/nature/journal/vaop/ncurrent/abs/nature10111.html

Funding for this research was provided by the National Institutes of Health, the Alkek Foundation, the National Institute of Diabetes and Digestive and Kidney Diseases, and the Robert R.P. Doherty Jr. - Welch Chair in Science.

About The Scripps Research Institute

The Scripps Research Institute (TSRI) is one of the world's largest independent, not-for-profit organizations focusing on research in the biomedical sciences. TSRI is internationally recognized for its contributions to science and health, including its role in laying the foundation for new treatments for cancer, rheumatoid arthritis, hemophilia, and other diseases. An institution that evolved from the Scripps Metabolic Clinic founded by philanthropist Ellen Browning Scripps in 1924, the institute now employs more than 2,500 people on its campuses in La Jolla, CA, and Jupiter, FL, where its renowned scientists—including two Nobel laureates and 20 members of the National Academies of Science, Engineering or Medicine—work toward their next discoveries. The institute's graduate program, which awards PhD degrees in biology and chemistry, ranks among the top ten of its kind in the nation. In October 2016, TSRI announced a strategic affiliation with the California Institute for Biomedical Research (Calibr), representing a renewed commitment to the discovery and development of new medicines to address unmet medical needs. For more information, see www.scripps.edu.

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Patrick Griffin, Ph.D. Chairman and Professor Department of Molecular Therapeutics
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