Dairy proteins and branched‐chain amino acids stimulate GLP‐1 release and downregulate genes involved in fatty acid and cholesterol metabolism in the human NCI‐H716 cell line

Abstract

The possibility that increased dairy intake can reduce body weight or exaggerate weight loss is attracting an increasing amount of attention. The objective of this work is to test the hypothesis that dairy proteins and branched-chain amino acids (BCAA) regulate satiety hormone secretion, and modulate selective genes involved in fatty acid and cholesterol metabolism. A human intestinal cell line was used to determine the dose effects of skim milk, casein, whey, leucine, isoleucine and valine on glucagon-like peptide-1 (GLP-1) release and the mRNA expression of i-FABP (intestinal type fatty acid binding protein), FATP4 (fatty acid transport protein), NPC1L1 (Niemann-Pick C1 like protein), ACC (acetyl CoA carboxylase), FAS (fatty acid synthase), SREBP-2 (sterol regulatory element-binding protein-2) and HMGCR [3-hydroxy-3-methylglutary-CoA (HMG-CoA) reductase]. The results showed that skim milk, casein, leucine and isoleucine stimulated GLP-1 release. Whey and isoleucine down-regulated the expressions of i-FABP, FATP4, NPC1L1, ACC, FAS, SREBP-2 and HMGCR. Skim milk and casein down-regulated the expression of ACC, FAS, and SREBP-2, but not i-FABP, FATP4 and NPC1L1. Leucine and valine down-regulated the expressions of NPC1L1, ACC, FAS, SREBP-2 and HMGCR, but not i-FABP, FATP4. The findings suggested that the anti-obesity effect of dairy may be mediated, in part, by integration of events that promote GLP-1 secretion and inhibit expression of genes involved in fatty acid and cholesterol absorption and synthesis. (Supported by CIHR and NSERC)