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A branched-chain amino acid-related metabolic signature that differentiates obese and lean humans and contributes to insulin resistance.

Publication ,  Journal Article
Newgard, CB; An, J; Bain, JR; Muehlbauer, MJ; Stevens, RD; Lien, LF; Haqq, AM; Shah, SH; Arlotto, M; Slentz, CA; Rochon, J; Gallup, D ...
Published in: Cell Metab
April 2009

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.

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Published In

Cell Metab

DOI

EISSN

1932-7420

Publication Date

April 2009

Volume

9

Issue

4

Start / End Page

311 / 326

Location

United States

Related Subject Headings

  • Thinness
  • Signal Transduction
  • Rats, Wistar
  • Rats
  • Obesity
  • Middle Aged
  • Metabolomics
  • Metabolome
  • Mass Spectrometry
  • Male
 

Citation

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Newgard, C. B., An, J., Bain, J. R., Muehlbauer, M. J., Stevens, R. D., Lien, L. F., … Svetkey, L. P. (2009). A branched-chain amino acid-related metabolic signature that differentiates obese and lean humans and contributes to insulin resistance. Cell Metab, 9(4), 311–326. https://doi.org/10.1016/j.cmet.2009.02.002
Newgard, Christopher B., Jie An, James R. Bain, Michael J. Muehlbauer, Robert D. Stevens, Lillian F. Lien, Andrea M. Haqq, et al. “A branched-chain amino acid-related metabolic signature that differentiates obese and lean humans and contributes to insulin resistance.Cell Metab 9, no. 4 (April 2009): 311–26. https://doi.org/10.1016/j.cmet.2009.02.002.
Newgard CB, An J, Bain JR, Muehlbauer MJ, Stevens RD, Lien LF, et al. A branched-chain amino acid-related metabolic signature that differentiates obese and lean humans and contributes to insulin resistance. Cell Metab. 2009 Apr;9(4):311–26.
Newgard, Christopher B., et al. “A branched-chain amino acid-related metabolic signature that differentiates obese and lean humans and contributes to insulin resistance.Cell Metab, vol. 9, no. 4, Apr. 2009, pp. 311–26. Pubmed, doi:10.1016/j.cmet.2009.02.002.
Newgard CB, An J, Bain JR, Muehlbauer MJ, Stevens RD, Lien LF, Haqq AM, Shah SH, Arlotto M, Slentz CA, Rochon J, Gallup D, Ilkayeva O, Wenner BR, Yancy WS, Eisenson H, Musante G, Surwit RS, Millington DS, Butler MD, Svetkey LP. A branched-chain amino acid-related metabolic signature that differentiates obese and lean humans and contributes to insulin resistance. Cell Metab. 2009 Apr;9(4):311–326.
Journal cover image

Published In

Cell Metab

DOI

EISSN

1932-7420

Publication Date

April 2009

Volume

9

Issue

4

Start / End Page

311 / 326

Location

United States

Related Subject Headings

  • Thinness
  • Signal Transduction
  • Rats, Wistar
  • Rats
  • Obesity
  • Middle Aged
  • Metabolomics
  • Metabolome
  • Mass Spectrometry
  • Male