Effects of intraduodenal infusion of the branched-chain amino acid leucine on ad libitum eating, gut motor and hormone functions, and glycemia in healthy men.
BACKGROUND
Branched-chain amino acids (BCAAs), particularly leucine, act as nutrient signals regulating protein synthesis and degradation as well as glucose metabolism. In addition, leucine has been demonstrated in animal experiments to modulate eating and energy homeostasis.


OBJECTIVE
We aimed to characterize the effects of physiologic and supraphysiologic loads of intraduodenal leucine on eating, gut hormone and motor functions, and blood glucose in humans.


METHODS
Twelve lean men were studied on 3 occasions in a randomized, double-blind order. Antropyloroduodenal motility, plasma ghrelin, cholecystokinin, glucagon-like peptide 1, peptide YY, insulin, glucagon, blood glucose, appetite perceptions, and gastrointestinal symptoms were measured during 90-min intraduodenal infusions of leucine at 0.15 kcal/min (total 3.3 g, 13.5 kcal), 0.45 kcal/min (total 9.9 g, 40.5 kcal), or saline (control). Ad libitum eating from a buffet lunch was quantified immediately after the infusions.


RESULTS
Leucine at 0.45 kcal/min inhibited eating (energy intake by ∼13%, P < 0.05), increased plasma cholecystokinin, slightly reduced blood glucose and increased plasma insulin, and decreased antral pressures (all P < 0.05). Leucine at 0.15 kcal/min had no effect on food intake, blood glucose, or antral pressures but also slightly increased plasma cholecystokinin (P < 0.05). Neither dose affected plasma ghrelin, glucagon, glucagon-like peptide 1 and peptide YY, or pyloric and duodenal pressures. Plasma leucine concentrations were related to the dose of intraduodenal leucine, with substantial increases during both 0.15 and 0.45 kcal/min.


CONCLUSIONS
The effects of intraduodenal infusions of free leucine on eating are probably not primarily mediated by changes in gut motor and hormone functions, with perhaps the exception of cholecystokinin. Instead, increased plasma leucine concentrations may be a potential signal mediating the eating-inhibitory effect of leucine. The study was registered as a clinical trial with the Australia and New Zealand Clinical Trial Registry (www.anzctr.org.au) as ACTRN12613000899741.
University of Adelaide Discipline of Medicine, Adelaide, Australia; National Health and Medical Research Council of Australia, Centre of Research Excellence in Translating Nutritional Science to Good Health, Adelaide, Australia; and re.steinert@gmail.com.
Robert E
RE
Steinert
University of Adelaide Discipline of Medicine, Adelaide, Australia;
Maria F
MF
Landrock
University of Adelaide Discipline of Medicine, Adelaide, Australia; National Health and Medical Research Council of Australia, Centre of Research Excellence in Translating Nutritional Science to Good Health, Adelaide, Australia; and.
Sina S
SS
Ullrich
University of Adelaide Discipline of Medicine, Adelaide, Australia; National Health and Medical Research Council of Australia, Centre of Research Excellence in Translating Nutritional Science to Good Health, Adelaide, Australia; and.
Scott
S
Standfield
Medizinische Klinik und Poliklinik IV, Klinikum der Universität München-Campus Innenstadt, Munich, Germany.
Bärbel
B
Otto
University of Adelaide Discipline of Medicine, Adelaide, Australia; National Health and Medical Research Council of Australia, Centre of Research Excellence in Translating Nutritional Science to Good Health, Adelaide, Australia; and.
Michael
M
Horowitz
University of Adelaide Discipline of Medicine, Adelaide, Australia; National Health and Medical Research Council of Australia, Centre of Research Excellence in Translating Nutritional Science to Good Health, Adelaide, Australia; and.
Christine
C
Feinle-Bisset
D000293:Adolescent; D000328:Adult; D001066:Appetite / Q000187:drug effects; D001786:Blood Glucose / Q000378:metabolism*; D015992:Body Mass Index; D002766:Cholecystokinin / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004386:Duodenum / Q000187:drug effects / Q000378:metabolism; D004435:Eating / Q000187:drug effects*; D002149:Energy Intake; D005768:Gastrointestinal Hormones / Q000097:blood*; D005769:Gastrointestinal Motility / Q000187:drug effects*; D054439:Ghrelin / Q000097:blood; D005934:Glucagon / Q000097:blood; D052216:Glucagon-Like Peptide 1 / Q000097:blood; D006801:Humans; D007328:Insulin / Q000097:blood; D007930:Leucine / Q000008:administration & dosage* / Q000097:blood; D008297:Male; D019894:Peptide YY / Q000097:blood; D055815:Young Adult
D001786:Blood Glucose; D005768:Gastrointestinal Hormones; D054439:Ghrelin; D007328:Insulin; D019894:Peptide YY; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D002766:Cholecystokinin; D007930:Leucine
cholecystokinin; food intake; glucagon; glucagon-like peptide 1; humans; insulin; peptide YY