title: Leucine acts in the brain to suppress food intake but does not function as a physiological signal of low dietary protein.
abstract: Intracerebroventricular injections of leucine are sufficient to suppress food intake, but it remains unclear whether brain leucine signaling represents a physiological signal of protein balance. We tested whether variations in dietary and circulating levels of leucine, or all three branched-chain amino acids (BCAAs), contribute to the detection of reduced dietary protein. Of the essential amino acids (EAAs) tested, only intracerebroventricular injection of leucine (10 μg) was sufficient to suppress food intake. Isocaloric low- (9% protein energy; LP) or normal- (18% protein energy) protein diets induced a divergence in food intake, with an increased consumption of LP beginning on day 2 and persisting throughout the study (P < 0.05). Circulating BCAA levels were reduced the day after LP diet exposure, but levels subsequently increased and normalized by day 4, despite persistent hyperphagia. Brain BCAA levels as measured by microdialysis on day 2 of diet exposure were reduced in LP rats, but this effect was most prominent postprandially. Despite these diet-induced changes in BCAA levels, reducing dietary leucine or total BCAAs independently from total protein was neither necessary nor sufficient to induce hyperphagia, while chronic infusion of EAAs into the brain of LP rats failed to consistently block LP-induced hyperphagia. Collectively, these data suggest that circulating BCAAs are transiently reduced by dietary protein restriction, but variations in dietary or brain BCAAs alone do not explain the hyperphagia induced by a low-protein diet.
authors.affiliation: Pennington Biomedical Research Center, Baton Rouge, Lousiana; and.
authors.forename: Thomas
authors.initials: T
authors.lastname: Laeger
authors.affiliation: Pennington Biomedical Research Center, Baton Rouge, Lousiana; and.
authors.forename: Scott D
authors.initials: SD
authors.lastname: Reed
authors.affiliation: Pennington Biomedical Research Center, Baton Rouge, Lousiana; and.
authors.forename: Tara M
authors.initials: TM
authors.lastname: Henagan
authors.affiliation: Pennington Biomedical Research Center, Baton Rouge, Lousiana; and.
authors.forename: Denise H
authors.initials: DH
authors.lastname: Fernandez
authors.affiliation: Virginia Polytechnic Institute and State University, Blacksburg, Virginia.
authors.forename: Marzieh
authors.initials: M
authors.lastname: Taghavi
authors.affiliation: Virginia Polytechnic Institute and State University, Blacksburg, Virginia.
authors.forename: Adele
authors.initials: A
authors.lastname: Addington
authors.affiliation: Pennington Biomedical Research Center, Baton Rouge, Lousiana; and.
authors.forename: Heike
authors.initials: H
authors.lastname: Münzberg
authors.affiliation: Pennington Biomedical Research Center, Baton Rouge, Lousiana; and.
authors.forename: Roy J
authors.initials: RJ
authors.lastname: Martin
authors.affiliation: Virginia Polytechnic Institute and State University, Blacksburg, Virginia.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Hutson
authors.affiliation: Pennington Biomedical Research Center, Baton Rouge, Lousiana; and morriscd@pbrc.edu.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Morrison
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D000597:Amino Acids, Branched-Chain / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D018753:Diet, Protein-Restricted / Q000009:adverse effects; D004044:Dietary Proteins / Q000494:pharmacology*; D004435:Eating / Q000187:drug effects* / Q000502:physiology; D006963:Hyperphagia / Q000209:etiology; D007276:Injections, Intraventricular; D007930:Leucine / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D023421:Models, Animal; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
chemical_list: D000596:Amino Acids; D000597:Amino Acids, Branched-Chain; D004044:Dietary Proteins; D007930:Leucine
keywords: branched-chain amino acids; food intake; hypothalamus; macronutrient; protein restriction