ArticleAmerican journal of physiology. Regulatory, integrative and comparative physiology2014
Leucine acts in the brain to suppress food intake but does not function as a physiological signal of low dietary protein.
Article in American journal of physiology. Regulatory, integrative and comparative physiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 62 citations in OpenAlex.
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- Manipulating dietary protein and amino acids in the common marmoset Callithrix jacchus impacts circulating metabolites and FGF21 levels.Scientific reports · 2025Article
- Brain amino acid sensing for organismal amino acid homeostasis.Open biology · 2025Review
- Leucine Reduced Blood-Brain Barrier Disruption and Infarct Size in Early Cerebral Ischemia-Reperfusion.Brain sciences · 2023Article
- Branched-Chain Amino Acids Are Linked with Alzheimer's Disease-Related Pathology and Cognitive Deficits.Cells · 2022Article
- Nutrient-Based Appetite Regulation.Journal of obesity & metabolic syndrome · 2022Review
- Lysine Deprivation Regulates Npy Expression via GCN2 Signaling Pathway in Mandarin Fish (International journal of molecular sciences · 2022Article
- Protein Appetite at the Interface between Nutrient Sensing and Physiological Homeostasis.Nutrients · 2021Review
- First evidence for the presence of amino acid sensing mechanisms in the fish gastrointestinal tract.Scientific reports · 2021Article
- Validation of a Feed Protocol in a Mouse Model That Mimics Marasmic Malnutrition.Frontiers in veterinary science · 2021Article
- Dietary Protein and Amino Acid Deficiency Inhibit Pancreatic Digestive Enzyme mRNA Translation by Multiple Mechanisms.Cellular and molecular gastroenterology and hepatology · 2021Article
- Animal Models of Undernutrition and Enteropathy as Tools for Assessment of Nutritional Intervention.Nutrients · 2019Review
- A review of the alleged health hazards of monosodium glutamate.Comprehensive reviews in food science and food safety · 2019Article
- FGF21 Signals Protein Status to the Brain and Adaptively Regulates Food Choice and Metabolism.Cell reports · 2019Article
- Methionine restriction prevents onset of type 2 diabetes in NZO mice.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
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.
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