Pla2g12b is critical for intestinal lipid absorption and C129Y is a dominant negative mutation

Nonetheless, the MUT mice had significantly lower plasma triglyceride (TG), cholesterol, HDL-C, LDL-C, apoB48, and apoB100 levels than WT mice. Several mechanisms for lower plasma lipids and lipoproteins in MUT mice were investigated. C129Y mutation had no effect on the expression of Pla2g12b and several other proteins necessary for lipid transport.

Therefore, the low plasma lipid levels in MUT mice were neither due to the absence of Pla2g12b protein nor due to reductions in critical proteins in lipid transport. Next, we addressed the role of Pla2g12b in hepatic lipid mobilization and intestinal lipid absorption. MUT livers exhibited normal TG synthesis, defective TG secretion, and enhanced fat accumulation.

MUT mice also showed defective intestinal fat absorption, intracellular lipid accumulation, and elevated fat excretion in the feces. We propose that Pla2g12b is critical for fat absorption and C129Y is a dominant negative mutation.