Studying fish to learn about fat

In mammals, most lipids (such as fatty acids and cholesterol) are absorbed into the body via the small intestine. The complexity of the cells and fluids that inhabit this organ make it very difficult to study in a laboratory setting. New research from Carnegie's Steven Farber, James Walters and Jennifer Anderson reveals a technique that allows scientists to watch lipid metabolism in live zebrafish.

This method enabled them to describe new aspects of lipid absorption that could have broad applications for human health. Their work is published in Chemistry & Biology.

The small intestine is composed of multiple cell types. It is also the site of microorganisms, bile and mucus that help digest and absorb food. In this environment, dietary lipids are digested by enzymes and bile so that the body, via the absorptive cells of the intestine called enterocytes, can take in critical nutrients.

One type of lipid, cholesterol, is known to impact a number of highly prevalent human diseases and is absorbed by enterocytes. In zebrafish and humans, newly absorbed cholesterol combines with proteins to form lipoproteins - vehicles destined for the lymphatic system for subsequent distribution throughout the body.

In humans, a protein called NPC1L1 (short for Niemann-Pick disease, type C1, gene-like 1) plays an important role in absorption by the enterocytes , but how this protein facilitates cholesterol's journey through the cell is poorly understood.

Another lipid metabolic product, called fatty acids, are absorbed by these same cells. Despite years of study, the physiological process by which proteins mediate the initial steps of fatty acid uptake is unclear. Once absorbed, the fatty acids are converted to triacyglycerides (fat) and either prepared to be transported out of the cell or transformed into droplets of stored fat. How these fat droplets form inside intestinal cells is not well understood.