Activation of the angiopoietin-like 4 (ANGPLT4) gene by milk fat and casein

Studies have shown a negative correlation between milk intake and obesity indicating that milk intake may impact on the regulation of body weight. Angiopoietin-like 4 (ANGPTL4) is suggested to be a regulator of lipid metabolism and is known to inhibit lipoprotein lipase. Milk-induced activation of ANGPTL4 gene expression and the mechanism behind it were investigated. Raw whole milk up-regulated ANGPTL4 mRNA ten-fold while skimming only exerted a five-fold up-regulation, as determined in the human epithelial colon cancer cell line HCT 116. Fractionation of the skimmed milk revealed an up-regulation of ANGPTL4 mRNA levels when exposed to casein, but no effects of the whey or residual cream fractions. Whole milk activated all three peroxisome proliferator-activated receptor (PPAR) subtypes in a dose-dependent manner, whereas skimmed milk only activated PPARα and casein had no effect. Thus, the fat fraction might be explained by PPAR activation but the effect of caseins needs further investigation.