A branched-chain amino acid-related metabolic signature that differentiates obese and lean humans and contributes to insulin resistance
- PMID: 19356713
- PMCID: PMC3640280
- DOI: 10.1016/j.cmet.2009.02.002
A branched-chain amino acid-related metabolic signature that differentiates obese and lean humans and contributes to insulin resistance
Erratum in
- Cell Metab. 2009 Jun;9(6):565-6
Abstract
Metabolomic profiling of obese versus lean humans reveals a branched-chain amino acid (BCAA)-related metabolite signature that is suggestive of increased catabolism of BCAA and correlated with insulin resistance. To test its impact on metabolic homeostasis, we fed rats on high-fat (HF), HF with supplemented BCAA (HF/BCAA), or standard chow (SC) diets. Despite having reduced food intake and a low rate of weight gain equivalent to the SC group, HF/BCAA rats were as insulin resistant as HF rats. Pair-feeding of HF diet to match the HF/BCAA animals or BCAA addition to SC diet did not cause insulin resistance. Insulin resistance induced by HF/BCAA feeding was accompanied by chronic phosphorylation of mTOR, JNK, and IRS1Ser307 and by accumulation of multiple acylcarnitines in muscle, and it was reversed by the mTOR inhibitor, rapamycin. Our findings show that in the context of a dietary pattern that includes high fat consumption, BCAA contributes to development of obesity-associated insulin resistance.
Figures
![Figure 1](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/3640280/bin/nihms99376f1.gif)
![Figure 2](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/3640280/bin/nihms99376f2.gif)
![Figure 3](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/3640280/bin/nihms99376f3.gif)
![Figure 4](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/3640280/bin/nihms99376f4.gif)
![Figure 5](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/3640280/bin/nihms99376f5.gif)
Similar articles
-
BCAA Supplementation in Mice with Diet-induced Obesity Alters the Metabolome Without Impairing Glucose Homeostasis.Endocrinology. 2021 Jul 1;162(7):bqab062. doi: 10.1210/endocr/bqab062. Endocrinology. 2021. PMID: 33765118 Free PMC article.
-
Diabetes and branched-chain amino acids: What is the link?J Diabetes. 2018 May;10(5):350-352. doi: 10.1111/1753-0407.12645. Epub 2018 Feb 13. J Diabetes. 2018. PMID: 29369529
-
Targeting BCAA Catabolism to Treat Obesity-Associated Insulin Resistance.Diabetes. 2019 Sep;68(9):1730-1746. doi: 10.2337/db18-0927. Epub 2019 Jun 5. Diabetes. 2019. PMID: 31167878 Free PMC article.
-
Insulin action, type 2 diabetes, and branched-chain amino acids: A two-way street.Mol Metab. 2021 Oct;52:101261. doi: 10.1016/j.molmet.2021.101261. Epub 2021 May 24. Mol Metab. 2021. PMID: 34044180 Free PMC article. Review.
-
Interplay between lipids and branched-chain amino acids in development of insulin resistance.Cell Metab. 2012 May 2;15(5):606-14. doi: 10.1016/j.cmet.2012.01.024. Cell Metab. 2012. PMID: 22560213 Free PMC article. Review.
Cited by
-
Metabolomic profiling of Prader-Willi syndrome compared with essential obesity.Front Endocrinol (Lausanne). 2024 May 15;15:1386265. doi: 10.3389/fendo.2024.1386265. eCollection 2024. Front Endocrinol (Lausanne). 2024. PMID: 38812813 Free PMC article.
-
Global status and trends of metabolomics in diabetes: A literature visualization knowledge graph study.World J Diabetes. 2024 May 15;15(5):1021-1044. doi: 10.4239/wjd.v15.i5.1021. World J Diabetes. 2024. PMID: 38766424 Free PMC article.
-
Amino acid restriction, aging, and longevity: an update.Front Aging. 2024 May 2;5:1393216. doi: 10.3389/fragi.2024.1393216. eCollection 2024. Front Aging. 2024. PMID: 38757144 Free PMC article. Review.
-
Acylcarnitine Abnormalities Implicate Mitochondrial Dysfunction in Patients With Neovascular Age-Related Macular Degeneration.Invest Ophthalmol Vis Sci. 2020 Jul 1;61(8):32. doi: 10.1167/iovs.61.8.32. Invest Ophthalmol Vis Sci. 2020. PMID: 38755790 Free PMC article.
-
Metabolomics Signature in Prediabetes and Diabetes: Insights From Tandem Mass Spectrometry Analysis.Endocrinol Diabetes Metab. 2024 May;7(3):e00484. doi: 10.1002/edm2.484. Endocrinol Diabetes Metab. 2024. PMID: 38739122 Free PMC article.
References
-
- An J, Muoio DM, Shiota M, Fujimoto Y, Cline GW, Shulman GI, Koves TR, Stevens R, Millington D, Newgard CB. Hepatic expression of malonyl-CoA decarboxylase reverses muscle, liver and whole-animal insulin resistance. Nat Med. 2004;10:268–74. - PubMed
-
- Ashley DVM, Fleury MO, Golay A, Maeder E, Leathwood PD. Evidence for diminished brain 5-hydroxytryptamine biosynthesis in obese diabetic and non-diabetic humans. Am J Clin Nutr. 1985;42:1240–1245. - PubMed
-
- Bjorbaek C, Kahn BB. Leptin signaling in the central nervous system and periphery. Recent Prog Horm Res. 2004;59:305–331. - PubMed
-
- Breum L, Rasmussen MH, Hilsted J, Fernstrom JD. Twenty-four hour plasma tryptophan concentrations and ratios are below normal in obese subjects and are not normalized by substantial weight reduction. Am J Clin Nutr. 2003;77:1112–1118. - PubMed
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Research Materials
Miscellaneous