Effect of L-Tryptophan and L-Leucine on Gut Hormone Secretion, Appetite Feelings and Gastric Emptying Rates in Lean and Non-Diabetic Obese Participants: A Randomized, Double-Blind, Parallel-Group Trial

Abstract

Background/ObjectivesGut hormones such as cholecystokinin (CCK) and glucagon-like peptide-1 (GLP-1) play a role as satiation factors. Strategies to enhance satiation peptide secretion could provide a therapeutic approach for obesity. Carbohydrates and lipids have been extensively investigated in relation to peptide release. In contrast, the role of proteins or amino acids is less clear. Our aim was to compare the effects of the amino acids L-tryptophan (L-trp) and L-leucine (L-leu) separately on gastric emptying and gut peptide secretion.Participants/MethodsThe study was conducted as a randomized (balanced), double-blind, parallel-group trial. A total of 10 lean and 10 non-diabetic obese participants were included. Participants received intragastric loads of L-trp (0.52 g and 1.56 g) and L-leu (1.56 g), dissolved in 300 mL tap water; 75 g glucose and 300 mL tap water served as control treatments.ResultsResults of the study are: i) L-trp at the higher dose stimulates CCK release (p = 0.0018), and induces a significant retardation in gastric emptying (p = 0.0033); ii) L-trp at the higher dose induced a small increase in GLP-1 secretion (p = 0.0257); iii) neither of the amino acids modulated subjective appetite feelings; and iv) the two amino acids did not alter insulin or glucose concentrations.ConclusionsL-trp is a luminal regulator of CCK release with effects on gastric emptying, an effect that could be mediated by CCK. L-trp’s effect on GLP-1 secretion is only minor. At the doses given, the two amino acids did not affect subjective appetite feelings.Trial RegistrationClinicalTrials.gov NCT02563847

Bidirectional Relationship between Gastric Emptying and Plasma Glucose Control in Normoglycemic Individuals and Diabetic Patients

“…In contrast with whole-structure proteins, intragastric administration of isolated amino acids such as lysine, leucine, or isoleucine does not seem to influence gastric emptying, even though it may reduce postprandial glycemic levels, most probably by direct stimulation of insulin secretion [ 69 , 70 ]. However, paradoxical results are also published, leaving the debate about free amino acid effects on gastric emptying still open [ 71 , 72 ]. Other three amino acids, histidine, glutamate, and aspartate, were reported to increase both postprandial glycemic levels, velocity of gastric emptying, and GLP-1 serum concentrations [ 71 ].…”

The Impact of the Use of Glycomacropeptide on Satiety and Dietary Intake in Phenylketonuria

“…It involves complex pathways that affect vagus-mediated signals, satiety related hormones and their metabolites (including the peptide ghrelin, cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1), glucose dependent insulinotropic polypeptide (GIP) and peptide tyrosine–tyrosine (PYY)) [ 11 , 15 , 20 , 21 , 22 , 23 ]. Some blood amino acids, particularly leucine, lysine, tryptophan, isoleucine and threonine, are linked to satiety responses [ 24 , 25 , 26 , 27 ]. CGMP is a small peptide and likely to be quickly absorbed [ 22 , 28 , 29 ].…”

l‐Glutamate stimulates cholecystokinin secretion via the T1R1/T1R3 mediated PLC/TRPM5 transduction pathway

“…Many clinical trials revealed that intraduodenal perfusion of individual amino acid decreased meal sizes through the release of CCK and GLP-1. 4,5 As a nonessential amino acid, L-glutamate (L-Glu), which is abundant naturally in commonly consumed proteins, plays a vital role in the regulation of host metabolism, growth, and immune response. 6,7 Research with rodents and pigs has confirmed that dietary supplementation with L-Glu/monosodium glutamate (MSG) reduced food consumption.…”