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Research Article

Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity

Elisa Fabbrini, Faidon Magkos, B. Selma Mohammed, Terri Pietka, Nada A. Abumrad, Bruce W. Patterson, Adewole Okunade, and Samuel Klein
PNAS first published August 24, 2009; https://doi.org/10.1073/pnas.0904944106
Elisa Fabbrini
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Faidon Magkos
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B. Selma Mohammed
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Terri Pietka
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Nada A. Abumrad
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Bruce W. Patterson
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Adewole Okunade
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Samuel Klein
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  • For correspondence: sklein@wustl.edu
  1. Edited by Jeffrey I. Gordon, Washington University School of Medicine, St. Louis, MO, and approved July 20, 2009 (received for review May 8, 2009)

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Abstract

Visceral adipose tissue (VAT) is an important risk factor for obesity-related metabolic disorders. Therefore, a reduction in VAT has become a key goal in obesity management. However, VAT is correlated with intrahepatic triglyceride (IHTG) content, so it is possible that IHTG, not VAT, is a better marker of metabolic disease. We determined the independent association of IHTG and VAT to metabolic function, by evaluating groups of obese subjects, who differed in IHTG content (high or normal) but matched on VAT volume or differed in VAT volume (high or low) but matched on IHTG content. Stable isotope tracer techniques and the euglycemic–hyperinsulinemic clamp procedure were used to assess insulin sensitivity and very-low-density lipoprotein–triglyceride (VLDL-TG) secretion rate. Tissue biopsies were obtained to evaluate cellular factors involved in ectopic triglyceride accumulation. Hepatic, adipose tissue and muscle insulin sensitivity were 41, 13, and 36% lower (P < 0.01), whereas VLDL-triglyceride secretion rate was almost double (P < 0.001), in subjects with higher than normal IHTG content, matched on VAT. No differences in insulin sensitivity or VLDL-TG secretion were observed between subjects with different VAT volumes, matched on IHTG content. Adipose tissue CD36 expression was lower (P < 0.05), whereas skeletal muscle CD36 expression was higher (P < 0.05), in subjects with higher than normal IHTG. These data demonstrate that IHTG, not VAT, is a better marker of the metabolic derangements associated with obesity. Furthermore, alterations in tissue fatty acid transport could be involved in the pathogenesis of ectopic triglyceride accumulation by redirecting plasma fatty acid uptake from adipose tissue toward other tissues.

  • abdominal fat
  • insulin resistance
  • NAFLD
  • steatosis
  • VLDL

Footnotes

  • 1To whom correspondence should be addressed at: Center for Human Nutrition, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8031, St. Louis, MO 63110. E-mail: sklein{at}wustl.edu
  • Author contributions: E.F., F.M., and S.K. designed research; E.F., B.S.M., T.P., and S.K. performed research; E.F., F.M., T.P., N.A.A., B.W.P., and A.O. analyzed data; and E.F., F.M., N.A.A., and S.K. wrote the paper.

  • Conflict of interest: The authors declare no conflict of interest.

  • This article is a PNAS Direct Submission.

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Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity
Elisa Fabbrini, Faidon Magkos, B. Selma Mohammed, Terri Pietka, Nada A. Abumrad, Bruce W. Patterson, Adewole Okunade, Samuel Klein
Proceedings of the National Academy of Sciences Aug 2009, pnas.0904944106; DOI: 10.1073/pnas.0904944106

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Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity
Elisa Fabbrini, Faidon Magkos, B. Selma Mohammed, Terri Pietka, Nada A. Abumrad, Bruce W. Patterson, Adewole Okunade, Samuel Klein
Proceedings of the National Academy of Sciences Aug 2009, pnas.0904944106; DOI: 10.1073/pnas.0904944106
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