ArticleBioFactors (Oxford, England)
Metabolic responses to dietary leucine restriction involve remodeling of adipose tissue and enhanced hepatic insulin signaling.
Article in BioFactors (Oxford, England). The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 54 citations in OpenAlex.
- Short-term dietary reduction of branched-chain amino acids reduces meal-induced insulin secretion and modifies microbiome composition in type 2 diabetes: a randomized controlled crossover trial.The American journal of clinical nutrition · 2019Trial
- Alterations in 3-Hydroxyisobutyrate and FGF21 Metabolism Are Associated With Protein Ingestion-Induced Insulin Resistance.Diabetes · 2017Trial
- Methionine-supplemented longevity diet increases growth hormone, GLP-1, and FGF21; reduces frailty; and promotes healthspan.Cell metabolism · 2026Article
- Dietary Insulinogenic Amino Acid Restriction Improves Glucose Metabolism in a Neonatal Piglet Model.Nutrients · 2025Article
- FGF21 as a mediator of adaptive changes in food intake and macronutrient preference in response to protein restriction.Neuropharmacology · 2024Review
- Modulation of GCN2/eIF2α/ATF4 Pathway in the Liver and Induction of FGF21 in Young Goats Fed a Protein- and/or Phosphorus-Reduced Diet.International journal of molecular sciences · 2023Article
- The Origins, Evolution, and Future of Dietary Methionine Restriction.Annual review of nutrition · 2022Review
- PAT2 regulates vATPase assembly and lysosomal acidification in brown adipocytes.Molecular metabolism · 2022Article
- Protein restriction and branched-chain amino acid restriction promote geroprotective shifts in metabolism.Aging cell · 2022Review
- Impacts of essential amino acids on energy balance.Molecular metabolism · 2022Review
- Protein Appetite at the Interface between Nutrient Sensing and Physiological Homeostasis.Nutrients · 2021Review
- The Role of Reduced Methionine in Mediating the Metabolic Responses to Protein Restriction Using Different Sources of Protein.Nutrients · 2021Article
- A fifty percent leucine-restricted diet reduces fat mass and improves glucose regulation.Nutrition & metabolism · 2021Article
- Low Protein Diets and Energy Balance: Mechanisms of Action on Energy Intake and Expenditure.Frontiers in nutrition · 2021Review
- Still Living Better through Chemistry: An Update on Caloric Restriction and Caloric Restriction Mimetics as Tools to Promote Health and Lifespan.International journal of molecular sciences · 2020Review
- Restriction of essential amino acids dictates the systemic metabolic response to dietary protein dilution.Nature communications · 2020Article
- Sexually Dimorphic Effects of Dietary Methionine Restriction are Dependent on Age when the Diet is Introduced.Obesity (Silver Spring, Md.) · 2020Article
- FGF21 and the Physiological Regulation of Macronutrient Preference.Endocrinology · 2020Review
- Article
- Influence of Diets with Varying Essential/Nonessential Amino Acid Ratios on Mouse Lifespan.Nutrients · 2019Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Dietary leucine was incrementally restricted to test whether limiting this essential amino acid (EAA) would fully reproduce the beneficial responses produced by dietary methionine restriction. Restricting leucine by 85% increased energy intake and expenditure within 5 to 7 days of its introduction and reduced overall accumulation of adipose tissue. Leucine restriction (LR) also improved glucose tolerance, increased hepatic release of fibroblast growth factor 21 into the blood stream, and enhanced insulin-dependent activation of Akt in liver. However, LR had no effect on hepatic lipid levels and failed to lower lipogenic gene expression in the liver. LR did affect remodeling of white and brown adipose tissues, increasing expression of both thermogenic and lipogenic genes. These findings illustrate that dietary LR reproduces many but not all of the physiological responses of methionine restriction. The primary differences occur in the liver, where methionine and LR cause opposite effects on tissue lipid levels and expression of lipogenic genes. Altogether, these findings suggest that the sensing systems which detect and respond to dietary restriction of EAAs act through mechanisms that both leucine and methionine are able to engage, and in the case of hepatic lipid metabolism, may be unique to specific EAAs such as methionine.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.