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


CONCLUSIONS
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.
Chen
Qixuan
Q
Faculty of Kinesiology and Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada.
Reimer
Raylene A
RA
D000818:Animals; D002364:Caseins / Q000494:pharmacology; D002460:Cell Line; D004044:Dietary Proteins / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D050612:Fatty Acid Transport Proteins / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D005786:Gene Expression Regulation; D052216:Glucagon-Like Peptide 1 / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects / Q000502:physiology; D007532:Isoleucine / Q000494:pharmacology; D007930:Leucine / Q000031:analogs & derivatives / Q000494:pharmacology*; D050356:Lipid Metabolism / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D008892:Milk; D008894:Milk Proteins / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D000067816:Whey Proteins
D002364:Caseins; D004044:Dietary Proteins; D050612:Fatty Acid Transport Proteins; D008894:Milk Proteins; D012333:RNA, Messenger; D000067816:Whey Proteins; D007532:Isoleucine; D052216:Glucagon-Like Peptide 1; D007930:Leucine