CC: Room 22/23
Much has been learned over the past decade about the basic molecular mechanisms of hepatic damage and inflammation fundamental for the development of various types of liver diseases, and ongoing research continues to provide important new insight. An expert panel of scientists will discuss two different, yet related, areas of current research during Friday’s Liver Cell Biology Special Interest Group Program, “Organelle Trafficking and Lipid Droplet Biology” beginning at 4:15 pm in Room 22/23, Moscone North/South.
The symposium will be divided into two halves, with the first half focusing on organelle trafficking effects and how they are relevant to liver diseases, according to Steven A. Weinman, MD, PhD, FAASLD, Professor and Vice Chair for Research in the Department of Internal Medicine and Director of the Liver Center at the University of Kansas Medical Center. Dr. Weinman will serve as moderator of the symposium alongside program co-chairs Natalia Nieto, PharmD, MSc, PhD, of the University of Illinois at Chicago, and Yasuko Iwakiri, PhD, of the Yale School of Medicine.
The mechanisms that produce exosomes in liver disease and how secretion of exosomes occurs upon inflammasome activation is one of the topics that will be covered in part one of the program.
“There’s been a huge advance over the last several years in our understanding of the role of exosomes in inflammatory diseases,” Dr. Weinman said. “In response to diseases, particularly inflammatory diseases, there is a big burst of exosome production that comes out of cells.”
Hepatocytes in the liver, for example, secrete exosomes that regulate the function of immune cells, sometimes making them cause more injury, sometimes less injury, Dr. Weinman said. Additionally, he noted, research has shown that fat cells in fatty tissue and adipocytes send out exosomes that regulate liver function.
“This is an emerging area and there’s a lot of research looking at what these exosomes do when they encounter other cells,” he said. “We’re learning more and more about the mechanisms, including previously unrecognized pathways, that link inflammatory stimuli to the production of exosomes.”
The first half of the program will also include a discussion on how lipid droplets move through the cell and how they interact with other organelles, such as lysosomes and mitochondria, and a presentation on the role of exosomes that are produced by immune cells and how they regulate fibrosis and the development of collagen.
The second half of the program will focus on lipid droplet biology and novel signaling pathways that contribute to the pathophysiology of liver disease and its resolution.
“This is a very exciting area of research with a lot of developments that have happened over the last 10 years or so,” Dr. Weinman said. “It was once thought that fat accumulated in the liver in big, inert globules. What we now know is that these structures that contain fat are not just oil droplets, but they are actually organelles called lipid droplets that give up their lipid under certain circumstances, and then take it in under others.”
The processes by which lipid droplets accumulate in the liver are very common, affecting about 20 percent of the population, he said, and are now recognized as one of the leading causes of advanced liver disease in the United States.
The topics scheduled for this part of the program include the functional role of de novo lipogenesis in oncogene-induced hepatocarcinogenesis, altered lipoprotein metabolism in nonalcoholic and alcoholic fatty liver diseases, and the role of the IRE1-alpha/XBP1 pathway in steatohepatitis.