A new technique allows scientists to visualize lipid metabolism in live zebrafish and to investigate aspects of lipid absorption that, until now, have remained poorly understood. The small intestine is the primary site of dietary lipid absorption in many vertebrates. The precise balance of nutrients, microorganisms and substances in the intestine is difficult to reproduce outside of a living organism, hindering study of the processes by which the body digests and absorbs dietary lipids in order to take in critical nutrients.

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Steven A. Farber and his team at the Carnegie Institution for Science (Baltimore, MD) developed a strategy for using fluorescence to visualize lipids and relevant proteins within the cells of the small intestines of live zebrafish larvae, which are transparent, in order to observe fat and cholesterol absorption. “Historically, the zebrafish has been used in the field of embryology and development and we felt that it had been underutilized for studies of whole-animal physiology,” Farber said in a press release. “Using the zebrafish in this novel way allowed us to be the first to observe cholesterol absorption in a living vertebrate system.”

Cholesterol and fatty acids are absorbed by intestinal cells called enterocytes. Newly absorbed fatty acids are either exported as lipoproteins or stored as fat droplets, but scientists know little about how the fate of fatty acids is determined. By studying fluorescent lipids in the zebrafish, the researchers were able to determine that fatty acid conversion depends on the level of fatty acids in the intestine: when fatty acid levels are high, fat storage in the form of lipid droplets is favored (Chem. Biol. 19, 1–13; 2012).

The scientists also used their method to investigate lingering questions about cholesterol absorption and how this process is related to the absorption of fatty acids. In the zebrafish, the researchers found that the presence of one type of fatty acid, oleic acid, is required for cholesterol uptake by enterocytes. Oleic acid also regulates the location within the enterocyte of the protein NPC1L1, which is integral to the process by which newly absorbed cholesterol combines with proteins to form lipoproteins. The intracellular location of NPC1L1 is fundamental to its role in promoting cholesterol uptake.

This study provides insights into the relationship between cholesterol and fatty acid metabolism that could have broad applications for human health. The researchers emphasize that their technique may be used in future studies to investigate other aspects of lipid metabolism as well.