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De novo lipogenesis in human fat and liver is linked to ChREBP-β and metabolic health

Author

Listed:
  • Leah Eissing

    (University Medical Center Hamburg-Eppendorf)

  • Thomas Scherer

    (Mount Sinai School of Medicine
    Present address: Division of Endocrinology and Metabolism, Department of Internal Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria)

  • Klaus Tödter

    (University Medical Center Hamburg-Eppendorf)

  • Uwe Knippschild

    (and Visceral Surgery, University of Ulm)

  • Jan Willem Greve

    (Atrium Medical Centre Parkstad)

  • Wim A. Buurman

    (NUTRIM School for Nutrition, Toxicology and Metabolism Research Maastricht, Maastricht University Medical Centre)

  • Hans O. Pinnschmidt

    (University Medical Center Hamburg-Eppendorf)

  • Sander S. Rensen

    (NUTRIM School for Nutrition, Toxicology and Metabolism Research Maastricht, Maastricht University Medical Centre)

  • Anna M. Wolf

    (and Visceral Surgery, University of Ulm)

  • Alexander Bartelt

    (University Medical Center Hamburg-Eppendorf)

  • Joerg Heeren

    (University Medical Center Hamburg-Eppendorf)

  • Christoph Buettner

    (Mount Sinai School of Medicine)

  • Ludger Scheja

    (University Medical Center Hamburg-Eppendorf)

Abstract

Clinical interest in de novo lipogenesis has been sparked by recent studies in rodents demonstrating that de novo lipogenesis specifically in white adipose tissue produces the insulin-sensitizing fatty acid palmitoleate. By contrast, hepatic lipogenesis is thought to contribute to metabolic disease. How de novo lipogenesis in white adipose tissue versus liver is altered in human obesity and insulin resistance is poorly understood. Here we show that lipogenic enzymes and the glucose transporter-4 are markedly decreased in white adipose tissue of insulin-resistant obese individuals compared with non-obese controls. By contrast, lipogenic enzymes are substantially upregulated in the liver of obese subjects. Bariatric weight loss restored de novo lipogenesis and glucose transporter-4 gene expression in white adipose tissue. Notably, lipogenic gene expression in both white adipose tissue and liver was strongly linked to the expression of carbohydrate-responsive element-binding protein-β and to metabolic risk markers. Thus, de novo lipogenesis predicts metabolic health in humans in a tissue-specific manner and is likely regulated by glucose-dependent carbohydrate-responsive element-binding protein activation.

Suggested Citation

  • Leah Eissing & Thomas Scherer & Klaus Tödter & Uwe Knippschild & Jan Willem Greve & Wim A. Buurman & Hans O. Pinnschmidt & Sander S. Rensen & Anna M. Wolf & Alexander Bartelt & Joerg Heeren & Christop, 2013. "De novo lipogenesis in human fat and liver is linked to ChREBP-β and metabolic health," Nature Communications, Nature, vol. 4(1), pages 1-11, June.
    • Handle: RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms2537
    DOI: 10.1038/ncomms2537
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    Cited by:

    1. Alexander J. Hu & Wei Li & Calvin Dinh & Yongzhao Zhang & Jamie K. Hu & Stefano G. Daniele & Xiaoli Hou & Zixuan Yang & John M. Asara & Guo-fu Hu & Stephen R. Farmer & Miaofen G. Hu, 2024. "CDK6 inhibits de novo lipogenesis in white adipose tissues but not in the liver," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    2. Anna Worthmann & Julius Ridder & Sharlaine Y. L. Piel & Ioannis Evangelakos & Melina Musfeldt & Hannah Voß & Marie O’Farrell & Alexander W. Fischer & Sangeeta Adak & Monica Sundd & Hasibullah Siffeti , 2024. "Fatty acid synthesis suppresses dietary polyunsaturated fatty acid use," Nature Communications, Nature, vol. 15(1), pages 1-13, December.

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