In Western nations, obesity and diabetes have led to a form of fatty liver disease (FLD) that, in certain individuals, can progress to cirrhosis and deadly liver cancer. How and why these life-threatening medical conditions develop remain unclear. This will be one of the topics of discussion at the Symposium on Metabolism at the 2017 ASCB|EMBO Meeting in Philadelphia.
The laboratory of Helen H. Hobbs, a Howard Hughes Medical Institute investigator at the University of Texas Southwestern Medical Center in Dallas, is using human genetics and advanced imaging techniques to reveal the molecular basis of FLD. In her talk, “Human Genetics Provides Molecular Handles to Elucidate Pathogenesis of Fatty Liver Disease,” Hobbs will explain how she used human genetics and 1H magnetic resonance spectroscopy to identify genetic risk factors contributing to fatty liver disease. Her group measured hepatic triglyceride (TG) content accumulation in a multiethnic population and discovered some startling results about how one’s genetic makeup influences one’s chance of developing FLD.
“We found significant differences in the prevalence of FLD among ethnic groups, suggesting that differences in genetic ancestry may influence the propensity for one to accumulate liver TG,” Hobbs said. “Using a genome-wide association study, we identified variants in two genes that confer susceptibility to FLD.”
Based on her findings, Hobbs also said that the role of TGs in liver disease progression may be similar to the role of LDL-cholesterol in coronary atherosclerosis. Chronic accumulation of TG in the liver promotes inflammation and fibrosis in a fashion that is similar to the relationship between LDL-cholesterol and atherosclerosis.
The other main topic of this symposium will be the role of mTOR (or mechanistic target of rapamycin) in cancer. Michael Hall of the Biozentrum, University of Basel, Switzerland will present the talk “mTOR Signaling in Growth and Metabolism.”
“I will talk about the role of mTOR in cancer, with regard to both mechanisms of evasive resistance to targeted therapies and the effector pathways via which mTOR drives tumorigenesis,” Hall said.
Disruption of the TOR network contributes to human illnesses such as diabetes and cancer and also has been implicated in a wide range of age-related disorders. Hall’s work shows that the TOR system adjusts cell size in response to the availability of raw materials and reveals an unanticipated linchpin of normal cell physiology.
Before Hall made these discoveries, cell growth was thought to be a passively regulated, spontaneous process that occurs when nutrients are available, without the help of an underlying regulatory system. These scientific breakthroughs have contributed to the understanding of the fundamental mechanisms that underlie growth, development, and aging.
The Symposium on Metabolism will be held Sunday, December 3, at 9:45 am.