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

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, Christoph Buettner and Ludger Scheja ()
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Leah Eissing: University Medical Center Hamburg-Eppendorf
Thomas Scherer: Mount Sinai School of Medicine
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

Nature Communications, 2013, vol. 4, issue 1, 1-11

Abstract: 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.

Date: 2013
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DOI: 10.1038/ncomms2537

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