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Interplay between Lipids and Branched-Chain Amino Acids in Development of Insulin Resistance
Open accessAbstract
Fatty acids (FA) and FA-derived metabolites have long been implicated in the development of insulin resistance and type 2 diabetes. Surprisingly, application of metabolomics technologies has revealed that branched-chain amino acids (BCAA) and related metabolites are more strongly associated with insulin resistance than many common lipid species. Moreover, the BCAA-related signature is predictive of incident diabetes and intervention outcomes and uniquely responsive to therapeutic interventions. Nevertheless, in animal feeding studies, BCAA supplementation requires the background of a high-fat diet to promote insulin resistance. This Perspective develops a model to explain how lipids and BCAA may synergize to promote metabolic diseases.
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“Thus, chronic elevations in incomplete oxidation of fatty acids and branched chain amino acids (Newgard, 2012) might foster a mitochondrial microenvironment that is conducive to ROS production.”
From Lipid-Induced Mitochondrial Stress and Insulin Action in Muscle (2012) · cites this paper as Newgard, 2012
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Metadata
- Authors
- Newgard, C. B.
- Affiliations
- Duke University (US)
- Corresponding author
- Newgard, Christopher B.
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2012-05
- Volume
- 15
- Issue
- 5
- Pages
- 606-614
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC3695706
- OpenAlex
- W2079195246
- Cited by
- 1,080
- References
- 58
- Citations by year
- 2026: 54 · 2025: 72 · 2024: 66 · 2023: 80 · 2022: 106 · 2021: 116 · 2020: 86 · 2019: 82 · 2018: 83 · 2017: 71 · 2016: 89 · 2015: 48 · 2014: 69 · 2013: 46 · 2012: 12
- FWCI
- 7.55
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Pfizer
- GlaxoSmithKline
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (P01DK058398)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- branched-chain amino acids, insulin resistance, type 2 diabetes, fatty acids, lipid metabolism, high-fat diet, BCAA supplementation, metabolomics, metabolic disorders, predictive biomarkers
- MeSH terms
- Amino Acids, Branched-Chain, Animals, Humans, Insulin Resistance, Metabolic Diseases, Lipid Metabolism
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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