During the Sunday afternoon symposium Nonalcoholic Steatohepatitis (NASH)—Emerging Concepts and Opportunities, four investigators will provide updates in four promising areas of NASH research. The two-hour symposium begins at 4:30 p.m. CT Sunday, June 14.

Liangyou Rui, PhD, the Louis G. D’Alecy Collegiate Professor of Physiology at the University of Michigan Medical School, will share new insights into the function of brown fat in liver disease. He will also discuss recent research into the epigenetic mechanisms involved in lipid accumulation.

Brown fat is well known for its protective affects against obesity, but it is less understood whether brown fat has obesity-independent effects. Recent research has uncovered examples of “lipid trafficking” by brown fat, Dr. Rui explained. Lipids are typically saved in white fat, then released into the blood and delivered to the target organs, providing energy. But if too much lipid is taken into an organ, it can lead to lipid accumulation.

“The brown fat seems to be involved in the control for this lipid trafficking,” said Dr. Rui, explaining that lipids can be rerouted to brown fat and oxidized to prevent lipid toxicity in organs, particularly in the liver.

“Secondarily, the brown fat can actively secrete some protective molecules,” Dr. Rui continued. “We call them the endocrine factors that can prevent hepatocyte injury, and therefore provide a second level of protection against liver disease. This function is independent of obesity and is really new.”

Ira Tabas, MD, PhD, Professor of Pathology and Cell Biology (in Physiology and Cellular Biophysics) at Columbia University Irving Medical Center, will share new research that aims to answer a 15-year-old mystery about why an increase in liver cholesterol is associated with patients’ progression from benign steatosis to fibrotic NASH. Dr. Tabas and his research team discovered a new mechanism linking liver cholesterol to NASH that has shown promise in the lab.

“We’ve used animal models to show how the mechanism of this link involved two types of liver cells talking to each other,” Dr. Tabas said. “One liver cell is the classic liver cell, the hepatocyte, and the cells that the hepatocyte talk to is the cell that is primarily responsible for fibrotic NASH, the hepatic stellate cell (HSC).”

In a paper published four years ago, the researchers reported that the transcription factor TAZ is increased in hepatocytes as benign steatosis progresses to fibrotic NASH. TAZ induces a number of genes, among them Indian hedgehog (Ihh), which gets secreted from the hepatocytes, interacts with HSCs, activates them into a pro-fibriotic program, and causes the progression of benign steatosis to fibrotic NASH.

The lab’s recent work addresses how hepatocyte TAZ is increased as steatosis progresses to NASH.

“The reason TAZ goes up in the liver is because of cholesterol,” Dr. Tabas said. “By sparking a set of signals in hepatocytes, cholesterol drives the increase in TAZ that begins this whole chain of events.”

Also during the session, Frank Tacke, MD, PhD, Chairman of Hepatology/Gastroenterology at Charité University Medical Center in Berlin, will present new insights into liver macrophages in NASH pathogenesis; and Laura Nagy, PhD, Professor of Molecular Medicine in Pathobiology and Gastroenterology at the Lerner Research Institute at Cleveland Clinic, will discuss inflammation and cell death in NASH.