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Hepatic expression of malonyl-CoA decarboxylase reverses muscle, liver and whole-animal insulin resistance.

Publication ,  Journal Article
An, J; Muoio, DM; Shiota, M; Fujimoto, Y; Cline, GW; Shulman, GI; Koves, TR; Stevens, R; Millington, D; Newgard, CB
Published in: Nat Med
March 2004

Lipid infusion or ingestion of a high-fat diet results in insulin resistance, but the mechanism underlying this phenomenon remains unclear. Here we show that, in rats fed a high-fat diet, whole-animal, muscle and liver insulin resistance is ameliorated following hepatic overexpression of malonyl-coenzyme A (CoA) decarboxylase (MCD), an enzyme that affects lipid partitioning. MCD overexpression decreased circulating free fatty acid (FFA) and liver triglyceride content. In skeletal muscle, levels of triglyceride and long-chain acyl-CoA (LC-CoA)-two candidate mediators of insulin resistance-were either increased or unchanged. Metabolic profiling of 36 acylcarnitine species by tandem mass spectrometry revealed a unique decrease in the concentration of one lipid-derived metabolite, beta-OH-butyrate, in muscle of MCD-overexpressing animals. The best explanation for our findings is that hepatic expression of MCD lowered circulating FFA levels, which led to lowering of muscle beta-OH-butyrate levels and improvement of insulin sensitivity.

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Published In

Nat Med

DOI

ISSN

1078-8956

Publication Date

March 2004

Volume

10

Issue

3

Start / End Page

268 / 274

Location

United States

Related Subject Headings

  • Triglycerides
  • Rats, Wistar
  • Rats
  • Muscle, Skeletal
  • Male
  • Liver
  • Lipid Metabolism
  • Insulin Resistance
  • Insulin
  • Immunology
 

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An, J., Muoio, D. M., Shiota, M., Fujimoto, Y., Cline, G. W., Shulman, G. I., … Newgard, C. B. (2004). Hepatic expression of malonyl-CoA decarboxylase reverses muscle, liver and whole-animal insulin resistance. Nat Med, 10(3), 268–274. https://doi.org/10.1038/nm995
An, Jie, Deborah M. Muoio, Masakazu Shiota, Yuka Fujimoto, Gary W. Cline, Gerald I. Shulman, Timothy R. Koves, Robert Stevens, David Millington, and Christopher B. Newgard. “Hepatic expression of malonyl-CoA decarboxylase reverses muscle, liver and whole-animal insulin resistance.Nat Med 10, no. 3 (March 2004): 268–74. https://doi.org/10.1038/nm995.
An J, Muoio DM, Shiota M, Fujimoto Y, Cline GW, Shulman GI, et al. Hepatic expression of malonyl-CoA decarboxylase reverses muscle, liver and whole-animal insulin resistance. Nat Med. 2004 Mar;10(3):268–74.
An, Jie, et al. “Hepatic expression of malonyl-CoA decarboxylase reverses muscle, liver and whole-animal insulin resistance.Nat Med, vol. 10, no. 3, Mar. 2004, pp. 268–74. Pubmed, doi:10.1038/nm995.
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 Mar;10(3):268–274.

Published In

Nat Med

DOI

ISSN

1078-8956

Publication Date

March 2004

Volume

10

Issue

3

Start / End Page

268 / 274

Location

United States

Related Subject Headings

  • Triglycerides
  • Rats, Wistar
  • Rats
  • Muscle, Skeletal
  • Male
  • Liver
  • Lipid Metabolism
  • Insulin Resistance
  • Insulin
  • Immunology