A protein found in cells lining the small intestines, FATP4, appears to control fat absorption and may provide a target for treating obesity.

Studies have shown that controlling the activity of FATP4 (blunting its activity) can reduce the amount of fat absorbed by the intestinal cells by up to 60%, according to Dr. Harvey Lodish from the Whitehead Institute for Biomedical Research in Cambridge, Massachusetts, and his team.

When fat reaches the intestines, a protein made by the pancreas breaks it down into smaller components called fatty acids and monoglycerides. The larger fatty acids cannot simply be absorbed by the cells; instead, proteins in the walls of intestinal cells must transport these long chain fatty acids (LCFA) into the cell.

The highest levels of FATP4 are located on the side of intestinal cells facing inside the intestines, where it comes into contact with fatty acids. FATP4 is the main fatty acid transporter found in the small intestines.

Cells in the laboratory in which FATP4 levels are artificially increased absorbed long chain fatty acids three times as fast as normal cells, according to the report. On the other hand, blocking FATP4 with compounds called antisense nucleotides decreased fatty acid absorption by 50% to 60%.

Taken together, these results show not only that FATP4 is involved in the transport of dietary fatty acids into enterocytes, but also that blocking FATP4 significantly reduces fatty acid uptake.

"Our... data have shown that such treatments could in principle result in drastic reduction of LCFA uptake by the small intestine, making FATP4 an attractive target for future antiobesity drugs," Lodish suggest.

SOURCE: Molecular Cell 1999;4:1-20.