When macrophages were incubated in the lab with a milky fluid containing lymph and fatty acids, Angptl4 showed reduced formation of lipid-laden foam cells, lower expression of inflammatory genes, and of a form of cellular stress.

The data show that Angptl4 is a key player in the protection against the severe proinflammatory effects of dietary saturated fat, the researchers conclude.

The findings may have implications for the approximately three percent of the human population who carry a mutation in the Angptl4 gene. "Based on our data in mice, it can be hypothesized that human subjects homozygous for the E40K mutation in Angptl4, which has reduced ability to inhibit LPL and is associated with lower plasma triglycerides, may be particularly sensitive to the proinflammatory effects of dietary saturated fat," the researchers wrote.

Kersten also speculates that Western diets loaded in saturated fats could perhaps overwhelm the system, particularly if it is "not working perfectly." The findings point more generally to an underappreciated role for the intestinal lymphatic system in managing the response to high concentrations of dietary fats.

Source: Cell Press