Fatty Liver Research Discovery With Implications For Obesity And Type 2 Diabetes

Diabetes Center researcher Allison Xu, PhD, is focused on understanding how the central nervous system regulates body weight and glucose levels. She studies how body weight is dependent on the brain sensing and responding to changes in energy stores in the body. Her exciting research often focuses on the hormone leptin and how it works in a critically important organ of the body, the liver.

The liver is responsible for changing fats eaten in the diet to types of fat that can be stored and used by the body. Hepatic steatosis, or fatty liver, is the collection of excessive amounts of triglycerides and other fats inside liver cells which, left untreated, can contribute to numerous illnesses. It has been generally thought to develop via peripheral mechanisms associated with obesity.

This month in the scientific journal Cell Metabolism, Dr. Xu and her team from UCSF, the San Francisco VA Medical Center, and the University of Michigan discovered that the hormone leptin will help suppress the fat content in the liver by stimulating the sympathetic nervous system’s control over the liver. They discovered that leptin can play this suppressive effect, independent of feeding and body weight -- if an enzyme that is involved in various cellular functions is present. If this leptin-induced enzyme, phosphatidylinositol 3-kinase (PI3K), is impaired or reduced, it leads to decreased liver activity and increased triglyceride levels -- without affecting obesity or key insulin signaling pathways in the liver.

This study is significant because conditions such as obesity and liver fat content are strongly correlated with insulin resistance. Thus, this study provides a new view on the role of central leptin resistance in causing obesity-associated fatty liver, insulin resistance and type 2 diabetes.

Dr. Xu is a member of the UCSF's Center for Obesity Assessment, Study and Treatment (COAST). Founded in 2004, COAST is focused on reducing the prevalence and adverse consequences of obesity. This group seeks to advance knowledge and understanding of the mechanisms by which stress influences obesity, and to develop effective interventions.