UCSF DIABETES, ENDOCRINOLOGY & METABOLISM TRAINING PROGRAM FACULTY RESEARCH SUMMARIES

Our research focuses on understanding lipid synthesis and energy metabolism in cells and organisms. Work in the laboratory falls into three major categories. The first is aimed at understanding the pathways and enzymes involved in neutral lipid synthesis and how they function in physiology and disease in whole organisms. Specifically, we study genes that encode enzymes in triglyceride and cholesterol ester biosynthesis and how they function in lipid metabolism in physiology and diseases such as atherosclerosis, obesity, and diabetes. Second, we study how these enzymes function in the storage of lipids in cells and how they contribute to lipid droplet formation. Finally, we are interested in processes that regulate energy expenditure in animals, with a particular emphasis on hormones and processes that regulate cellular fat storage and oxidation.

The accumulation of lipids in tissues plays a central role in diseases that are major worldwide health concerns. For example, triglyceride accumulation in adipose tissue gives rise to obesity. In addition, triglyceride deposition in other tissues is associated with the development of diseases such as diabetes, steatohepatitis, and cardiomyopathy. We are studying the pathways and enzymes that synthesize these lipids to understand the basic mechanisms and determine their role in disease. Our research has identified several potential targets for new therapies.

We use a variety of approaches, including cell culture models and genetically modified mice. Our work spans multiple research disciplines, from molecular biology to lipid biochemistry to whole organism physiology. Ultimately, we are interested in both the fundamental biology of lipid metabolism at the molecular level and how this basic research relates to physiology and disease. 

We have identified and cloned many of the genes that encode important enzymes in neutral lipid synthesis, and we have elucidated the functions of these enzymes in physiology and disease. For example, we defined the functional roles of acyl CoA:cholesterol acyltransferase (ACAT) enzymes in systemic cholesterol metabolism and atherosclerosis. We also identified the mammalian acyl CoA:diacylglycerol acyltransferase (DGAT) genes and elucidated their roles in mammalian triglyceride and energy metabolism.

Selected References

Buhman, K.K., Accad, M., Novak, S., Choi, R.S., Wong, J.S., Hamilton, R.L., and Farese, R.V., Jr. (2000) Resistance to diet-induced hypercholesterolemia and gallstone formation in ACAT2-deficient mice. Nat. Med. 6:1341–1347.

Chen, H.C., Jensen, D.R., Myers, H.M., Eckel, R.H., and Farese, R.V., Jr. (2003) Obesity resistance and enhanced glucose metabolism in mice transplanted with white adipose tissue lacking acyl CoA:diacylglycerol acyltransferase 1. J. Clin. Invest. 111:1715–1722.

Stone, S., Myers, H.M., Brown, B., Watkins, S. , Feingold K., Elias P., and Farese, R.V., Jr. (2004) Lipopenia and skin barrier abnormalities in DGAT2-deficient mice. J. Biol. Chem. 279:11767–11776.

Website: http://www.gladstone.ucsf.edu/gladstone/php/?sitename=farese

back to faculty list