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Lipid partitioning, incomplete fatty acid oxidation, and insulin signal transduction in primary human muscle cells: effects of severe obesity, fatty acid incubation, and fatty acid translocase/CD36 overexpression.

Publication ,  Journal Article
Bell, JA; Reed, MA; Consitt, LA; Martin, OJ; Haynie, KR; Hulver, MW; Muoio, DM; Dohm, GL
Published in: J Clin Endocrinol Metab
July 2010

CONTEXT: Intracellular lipid partitioning toward storage and the incomplete oxidation of fatty acids (FA) have been linked to insulin resistance. OBJECTIVE: To gain insight into how intracellular lipid metabolism is related to insulin signal transduction, we examined the effects of severe obesity, excess FA, and overexpression of the FA transporter, FA translocase (FAT)/CD36, in primary human skeletal myocytes. DESIGN, SETTING, AND PATIENTS: Insulin signal transduction, FA oxidation, and metabolism were measured in skeletal muscle cells harvested from lean and severely obese women. To emulate the obesity phenotype in our cell culture system, we incubated cells from lean individuals with excess FA or overexpressed FAT/CD36 using recombinant adenoviral technology. RESULTS: Complete oxidation of FA was significantly reduced, whereas total lipid accumulation, FA esterification into lipid intermediates, and incomplete oxidation were up-regulated in the muscle cells of severely obese subjects. Insulin signal transduction was reduced in the muscle cells from severely obese subjects compared to lean controls. Incubation of muscle cells from lean subjects with lipids reduced insulin signal transduction and increased lipid storage and incomplete FA oxidation. CD36 overexpression increased FA transport capacity, but did not impair complete FA oxidation and insulin signal transduction in muscle cells from lean subjects. CONCLUSIONS: Cultured myocytes from severely obese women express perturbations in FA metabolism and insulin signaling reminiscent of those observed in vivo. The obesity phenotype can be recapitulated in muscle cells from lean subjects via exposure to excess lipid, but not by overexpressing the FAT/CD36 FA transporter.

Duke Scholars

Published In

J Clin Endocrinol Metab

DOI

EISSN

1945-7197

Publication Date

July 2010

Volume

95

Issue

7

Start / End Page

3400 / 3410

Location

United States

Related Subject Headings

  • Signal Transduction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Obesity, Morbid
  • Muscle Fibers, Skeletal
  • Insulin Resistance
  • Insulin
  • Humans
  • Female
  • Fatty Acids
  • Fatty Acid Transport Proteins
 

Citation

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ICMJE
MLA
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Bell, J. A., Reed, M. A., Consitt, L. A., Martin, O. J., Haynie, K. R., Hulver, M. W., … Dohm, G. L. (2010). Lipid partitioning, incomplete fatty acid oxidation, and insulin signal transduction in primary human muscle cells: effects of severe obesity, fatty acid incubation, and fatty acid translocase/CD36 overexpression. J Clin Endocrinol Metab, 95(7), 3400–3410. https://doi.org/10.1210/jc.2009-1596
Bell, Jill A., Melissa A. Reed, Leslie A. Consitt, Ola J. Martin, Kimberly R. Haynie, Matthew W. Hulver, Deborah M. Muoio, and G Lynis Dohm. “Lipid partitioning, incomplete fatty acid oxidation, and insulin signal transduction in primary human muscle cells: effects of severe obesity, fatty acid incubation, and fatty acid translocase/CD36 overexpression.J Clin Endocrinol Metab 95, no. 7 (July 2010): 3400–3410. https://doi.org/10.1210/jc.2009-1596.
Journal cover image

Published In

J Clin Endocrinol Metab

DOI

EISSN

1945-7197

Publication Date

July 2010

Volume

95

Issue

7

Start / End Page

3400 / 3410

Location

United States

Related Subject Headings

  • Signal Transduction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Obesity, Morbid
  • Muscle Fibers, Skeletal
  • Insulin Resistance
  • Insulin
  • Humans
  • Female
  • Fatty Acids
  • Fatty Acid Transport Proteins