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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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