Distinguished Seminar Series

December 8, 2014 - 1:30pm to 2:30pm

Speaker: Xiao-Ming Yin, M.D., Ph.D.                        

Director of Clinical Laboratories, Indiana University                                                                                                                      Health Pathology Laboratory and Vice Chairman for Clinical  Pathology                                                                                       Department of Pathology and Laboratory Medicine                                                                                                                        Indiana University, School of Medicine

 Seminar Title: "Autophagy in Fatty Liver Disease”

Hosted by Dr. Ekihiro Seki, UCSD SRC Project Leader

December 19, 2014 | Meeting Summary By: Mei-Fei Yueh, Ph.D.                                                                                                Web content: Michelle Feiock, Program Manager and Bethany Behnke, Assistant

Meeting Summary

     In the Distinguished Seminar Series, we were honored to have as our speaker Xiao-Ming Yin, M.D., Ph.D., the Louis Y. Mazzini Professor of Pathology and Director of Clinical Laboratories, Indiana University Health Pathology Laboratory. One of his laboratory research focuses is the regulation of macroautophagy in liver disease. Macroautophagy (“autophagy”) - an intracellular degradation system encoded by a number of ATG genes – is responsible for the degradation of macromolecules and subcellular organelles and is most closely associated with human disease (compared to microautophagy and chaperone-mediated autophagy). As autophagy is commonly activated in response to a variety of stress conditions (such as starvation), Dr. Yin’s laboratory has been exploring how autophagy regulates cellular homeostasis in hepatocytes in response to ethanol- or high fat diet (HFD)-induced liver pathogenesis.

     Previous studies in Dr. Yin’s laboratory have demonstrated that ethanol could induce the autophagy process in primary hepatocytes dependent on ethanol metabolism (by CYP2E1), ROS generation, and mTOR inhibition. It is also known that autophagy has the ability to remove and decrease intracellular lipid droplets. Fatty liver disease – including alcohol and non-alcoholic fatty liver conditions – is the early response of liver pathogenesis, can progress and manifest to steatohepatitis, fibrosis, and cirrhosis, and has significantly increased in the era of obesity epidemic. By promoting or inhibiting autophagy through pharmacological modulators of autophagy, Dr. Yin’s laboratory conducted a series of experiments and examined the impact of autophagy on fatty liver due to ethanol feeding or high fat diet.

UCSD SRC Speaker Dr. Xiao-Ming Yin

Dr. Yin presenting his research on fatty liver disease

   
    They found that both carbamazepine and rapamycin – acting as autophagy activators by suppressing mTOR activity - promote autophagy in hepatocytes. When mice were treated with these autophagy activators, they reduce steatosis, liver injury, ALT elevation, and lipid droplets following acute or chronic ethanol feeding in mice. In contrast, chloroquine, which blocks autophagy, exacerbates stenosis, the accumulation of lipid droplets, and liver injury in these animals. In combination with previous results, Dr. Yin concluded that although ethanol-induced autophagy did not affect protein degradation, it is selective for damaged mitochondria and accumulated droplets and plays a protective role by limiting ethanol-induced liver toxicity.

    To explore fatty liver disease induced by a high fat diet (HFD), Dr. Yin’s team found that carbamazepine and rapamycin significantly reduce stenosis, hepatic and serum triglycerides, and insulin resistance when mice were fed a HFD for 12 weeks, indicating that autophagy inducing agents are benefiting fatty liver by increasing autophagy.  These studies point out the potential treatment of fatty liver due to ethanol or HFD by stimulating autophagic flow using pharmacological modulators.

    The transcription factor EB (TFEB) has been identified as one of the transcription factors that regulate autophagy gene expression. Following a HFD feeding in mice, Dr. Yin’s laboratory discovered the following signaling events: mTOR can be activated through a HFD, which in turn suppresses TFEB, subsequently affects lysosome function, and returns back to regulate mTOR activation, forming an mTOR-TFEB feedback loop and contributing to autophagy degradation. Another phenomenon they discovered is that mTOR modulation is rather dynamic and exhibits an oscillation pattern, which is conversely correlated with TFEB and lysosome activities at the different time points throughout the course of HFD treatment. These studies imply that suppression of mTOR and promotion of TFEB along with autophagy enhancement may be an effective therapeutic approach for treating fatty liver disease.   

divider1

Xiao-Ming Yin, MD, PhD

Mazzini Professor, Vice Chairman for Clinical Pathology, Director of Clinical Laboratories
PubMed Link
Research Information

IU Health Pathology Laboratory
350 West 11th Street, Room 6016A
Indianapolis, IN 46202-4108
Phone: 317-491-6096
Fax: 317-491-6639
E-mail: xmyin@iupui.edu

 

Upcoming Events

There are no events to display.

Past Events

May 13, 2015 - 12:00pm to 1:00pm

Project 5- Seki
"The Enhancement of Toxin-Induced Liver Fibrosis in Fatty Liver Disease"

April 8, 2015 - 12:00pm to 1:00pm

Project 7- Schroeder
"Molecular Mechanisms of Heavy Metal Detoxification and Accumulation in Plants"

March 11, 2015 - 12:00pm to 1:00pm

SALK/Project 3 - Evans/Lu
"Nuclear receptors and their roles in mammalian response to environmental stressors"

February 11, 2015 - 12:00pm to 1:00pm

Project 1- Karin
"Stress and Liver Cancer- the p62 connection"

January 14, 2015 - 12:00pm to 1:00pm

Project 5 - Brenner
"Approaches to Inhibit Carbon Tetrachloride Induced Liver Fibrosis"

December 10, 2014 - 12:00pm to 1:00pm

CEC/RTC: Pezzoli/Al-Delaimy/Zaslavsky
"Land Use and Public Health: An integrated approach to Superfund toxicants in urban agriculture, stormwater, and dust"

December 8, 2014 - 1:30pm to 2:30pm

Speaker: Xiao-Ming Yin, M. D., Ph. D., Mazzini Professor, Vice Chairman for Clinical Pathology, Director of Clinical Laboratories, Indiana University, School of Medicine
"Autophagy in Fatty Liver Disease"

November 19, 2014 - 12:00pm to 1:00pm

TSRI/Project 2 - Russell/Ganguly
"Functional Profiling and Bioassays in Fission Yeast for Assessing Genetic Pathways Affecting Cellular Sensitivity to Chromium and other Metal Toxicants"

November 12, 2014 - 8:45am to November 14, 2014 - 2:00pm

The 2014 Superfund Research Program (SRP) annual meeting --hosted by UC Berkeley's Superfund Research Center and the NIEHS.

October 8, 2014 - 12:00pm to 1:00pm

PROJECT 4 - TUKEY/YUEH
"The commonly used antimicrobial additive triclosan is a liver tumor promoter"

Pages

Contact

UCSD Superfund Research Center
University of California, San Diego
Pharmacology Department
9500 Gilman Drive, Mail Code 0722
La Jolla, CA 92093-0722