Ilya Levental, PhD, associate professor in the Department of Integrative Biology and Pharmacology, saw his paper “Lipidomic and biophysical homeostasis of mammalian membranes in 1 response to dietary lipids is essential for cellular fitness,” published in March issue of Nature Communications.
“Our lab is interested in how dietary fats affect cell function,” Levental said. “It is widely known that diet is a foremost contributor to health and disease, but often these are just correlations without clear mechanisms.”
The lab used lipidomics, like genomics for lipids, which is the study of lipid metabolism to better understand the biochemical mechanisms in specific changes in lipid metabolism. They treated cells with dietary fats, like docosahexaenoic acid (DHA) and manipulated mouse diets. After isolating lipids from the tissues, the lab measured in detail the different lipids present in the cells.
“To our great surprise, we found that a very large portion of the lipids in our cells comes straight from the diet,” Levental said. “Close to one-third of a given tissue may be made of something our cells themselves do not make.”
Levental and the lab fed fish oil to cells and mice. After measuring the lipidomes, the lab discovered the presence of w-3 polyunsaturated fats, which are not produced by mammals, meaning they must come directly from the diet.
“The question for us became, how is it possible that cells don’t care what their lipids are,” Levental said. “The stuff coming from the diet always changes, which means cell membranes are also always changing. That’s very surprising since lipids and membranes play essential roles in almost all cell functions.”
This question led to the discovery that rather than working as a restriction against what comes into the cell, the cells regulate membranes on the “back end.” The cells sense collective membrane properties – how fluid, they are, how permeable they are, how stiff they are – and they regulate those properties. When the cells are unable to regulate those properties, the cell dies.
“We’ve discovered that mammalian cells sense lipid membrane physical properties, and that they need to do this to homeostatically deal with constant variable inputs from dietary fats,” Levental said. “This adaptation appears to be essential for homeostasis in mammals.”
Going forward, research in the Levental Lab will advance to better understand what this research means for human health.
“We believe that the fact that dietary fats are actually incorporated into our cells, they must be important to their function,” Levental said. “If we can understand how this works, maybe we can manipulate it with drugs or diet.”
Research in the lab was driven by Kandice R. Levental, PhD, assistant professor of integrative biology and pharmacology. Robb Chapkin, PhD, Allen Endowed Chair in Nutrition & Chronic Disease at the Texas A&M University College of Agriculture & Life Sciences guided the lab on animal experience and provided tissue samples.