Dairy protein and leucine alter GLP-1 release and mRNA of genes involved in intestinal lipid metabolism in vitro

Abstract

Objective A growing body of evidence supports an antiobesity effect of dairy products; however, the mechanisms remain unclear. The objective of this study was to explore possible intestinal mechanisms by which dairy delivers an antiobesity effect. The human intestinal cell line, NCI-H716, was used to test the hypothesis that branched-chain amino acids and dairy proteins regulate satiety hormone secretion and modulate genes involved in fatty acid and cholesterol metabolism. Methods In dose–response (0.5%, 1.0%, 2.0%, and 3.0%) studies, the effect of leucine, isoleucine, valine, skim milk, casein, and whey on glucagon-like peptide-1 release and the expression of selected genes were tested. Results Leucine, isoleucine, skim milk, and casein stimulated glucagon-like peptide-1 release ( P < 0.05). Isoleucine and whey downregulated the expression of intestinal-type fatty acid binding protein ( i-FABP), fatty acid transport protein 4 ( FATP4), Niemann-Pick C-1–like-1 protein ( NPC1L1), acetyl-coenzyme A carboxylase ( ACC), fatty acid synthase ( FAS), sterol regulatory element-binding protein-2 ( SREBP-2), and 3-hydroxy-3-methylglutaryl-CoA reductase ( HMGCR; P < 0.05). Leucine and valine downregulated the expression of NPC1L1, ACC, FAS, SREBP-2, and HMGCR ( P < 0.05). Casein downregulated the expression of i-FABP, FATP4, ACC, FAS, SREBP-2, and HMGCR ( P < 0.05). Skim milk downregulated the expression of ACC, FAS, and SREBP-2, but not i-FABP, FATP4, and NPC1L1. Conclusion This work suggests that the antiobesity effect of dairy may be mediated, at least in part, by integration of events that promote glucagon-like peptide-1 secretion and inhibit expression of genes involved in intestinal fatty acid and cholesterol absorption and synthesis.