Lipids are a large and diverse group of naturally occurring molecules known to most of us as cholesterol, fatty acids, triglycerides, etc.
For decades, researchers have studied the complex process of lipid metabolism — the uptake of processing, storing and disposing of these molecules — because they have very fundamental functions not only in energy storage, but also are very important mediators of various events between cells and intercellular activity. In addition to playing a role in diabetes and obesity, they’re now being linked to cancer.
At MD Anderson, Ivan Uray, M.D., Ph.D., assistant professor in Clinical Cancer Prevention, is focusing on the fast-growing field of lipidomics — the study of cellular lipids and lipid-mediated signaling pathways in biological systems — to investigate a lipogenic enzyme that, as part of a maladaptive process, may promote cancer development.
“It’s important that we understand this underserved area of research because obesity, diabetes and insulin resistance are risk factors for breast cancer,” he says. “On the other hand, it’s difficult to establish reliable, accurate methods to answer scientific questions pertaining to the study of lipids because they’re not water soluble and, therefore, cannot easily be studied by the same methods as proteins and sugars.”
He and his team are studying diacylglycerol acyltransferase (DGAT1), a lipogenic enzyme responsible for making complex lipids for storage, which is amplified in 5% to 20% of cancer cases.
“Our research is unique because this enzyme has never been studied in cancer,” Uray says.
In a grant recently funded by the National Cancer Institute, he and his team are investigating the potential of suppressing DGAT1 activity to prevent or delay breast cancer.
The other important aspect of studying this enzyme is that drugs have already been developed and are currently being clinically tested as a treatment for type II diabetes and obesity. In preclinical studies, data showed that mice lacking DGAT1 were leaner, had higher insulin sensitivity and lived longer.
“If we can find a way to better control obesity and diabetes, we can also reduce the risk of cancer,” Uray says.
The facts are daunting
More than one-third of U.S. adults are obese with medical costs of $147 billion in 2008 alone.
Yet, according to the Centers for Disease Control and Prevention, obesity-related conditions — heart disease, stroke, type 2 diabetes and certain types of cancer — cause deaths that might have been prevented.
At MD Anderson, the condition, increasingly referred to as a disease itself, is being addressed on several fronts by behavioral scientists, epidemiologists and clinical cancer prevention experts.