Some UCLA researchers focus on manipulating the performance of mitochondria (the cell’s energy-burning engine) and other cell structures. Meanwhile, their scientific colleagues are taking a genetic approach to understanding metabolism and metabolic disorders.
Peter Tontonoz, PhD, a professor of pathology and laboratory medicine, studies the genetic components of obesity as a disorder of energy balance. His lab also studies Type 2 diabetes as a disorder of lipid, or fat, metabolism.
Lipids include triglycerides and cholesterols. Lipid metabolism involves all aspects of lipids coming into the body and either being stored in fat cells or burned for energy in mitochondria.
Tontonoz studies how genes are regulated in response to lipid metabolism. He has researched ways to slow the process of metabolism or speed it up.
“At its essence, obesity is a disorder of energy balance, and type 2 diabetes is a disorder of lipid, or fat, metabolism.”
- Dr. Peter Tontonoz
He and his colleagues have identified enzymes called liver X receptors (LXRs) that are master regulators of cholesterol, fat and inflammatory gene expression. LXRs regulate fatty acid synthesis and lipid use in the brain. Loss of LXRs appears to influence the development of metabolic disorders.
The role of this enzyme has provided the possibility of developing LXR inhibitors for clinical use.
When stimulated, LXRs "turn on" several hundred genes that hold instructions to create proteins for carrying out bodily processes in cells, from transporting and excreting cholesterol to synthesizing fat in the liver. Evidence also shows that they suppress inflammatory processes in several contexts.
In mice, compounds that turn on the receptors have been shown to lower cholesterol levels in blood and liver tissues, effectively treating: