Mutation blocks fat absorption

A newly discovered gene in zebrafish seems to prevent the animals from absorbing fat molecules from their diets. The finding could lead to new strategies to fight obesity, high cholesterol, and other lipid-related disorders in people.

Five years ago, Baltimore-based Steven A. Farber of the Carnegie Institution of Washington (D.C.) and his colleagues discovered mutant zebrafish larvae that don’t absorb lipids from dietary fat. Since all cells need fat to function properly, this disorder killed the larvae soon after they hatched. The researchers suspected that a single gene was altered in the mutant fish.

In a new study, published in the April Cell Metabolism, Farber’s team zeros in on a gene that the researchers call fat-free (ffr). It’s on the fish’s chromosome 10. When the team inserted normal ffr into fish embryos carrying the mutant gene, the resulting larvae could process lipids as well as healthy zebrafish could.

To determine the gene’s function, the researchers examined mutant fish larvae under the microscope. Compared with healthy larvae, the mutants’ intestinal cells had grossly enlarged Golgi bodies, cell structures that process lipids and proteins. Rather than leaving these structures after processing, lipids in the mutant animals’ cells became trapped inside.

Farber notes that the new findings give researchers a better understanding of how cells process lipids. Scientists may eventually exploit this knowledge to selectively control lipid processing throughout the body, he adds.