Metabolic responses to dietary leucine restriction involve remodeling of adipose tissue and enhanced hepatic insulin signaling
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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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FGF21 is also increased by the restriction of individual amino acids.
“with FGF21 also being increased by the restriction of individual amino acids”
From FGF21 and the physiological regulation of macronutrient preference (2020) · cites this paper as [154]
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- Authors
- Wanders, D., Stone, K. P., Dille, K., Simon, J., Pierse, A., & Gettys, T. W.
- Affiliations
- Georgia State University (US)
- Pennington Biomedical Research Center (US)
- Corresponding author
- Gettys, Thomas W.
- Venue
- BioFactors
- Publisher
- Wiley
- Published
- 2015-11-12
- Volume
- 41
- Issue
- 6
- Pages
- 391-402
- ISSN
- 0951-6433 (ISSN-L)
- 1872-8081
- PMC
- PMC4715699
- OpenAlex
- W2196344142
- Cited by
- 57
- References
- 40
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 1 · 2023: 1 · 2022: 5 · 2021: 9 · 2020: 6 · 2019: 9 · 2018: 6 · 2017: 7 · 2016: 4
- FWCI
- 4.18
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- BioFactors (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (DK‐096311, F32 DK098918, P20‐GM103528, 2P30 DK072476)
- Topics
- Health Sciences › Medicine › Physiology › Dietary Effects on Health
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- methionine restriction, essential amino acids, adipose tissue remodeling, white adipose tissue, brown adipose tissue, hepatic insulin signaling, Akt, FGF21, glucose tolerance, energy expenditure, lipogenic gene expression, hepatic lipid metabolism, thermogenesis
- MeSH terms
- Adipose Tissue, Amino Acids, Essential, Animals, Fibroblast Growth Factors, Glucose, Humans, Insulin, Leucine, Liver, Methionine, Signal Transduction, Dietary Supplements, Mice
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