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Macrophage VLDLR mediates obesity-induced insulin resistance with adipose tissue inflammation

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  • Kyung Cheul Shin

    (National Creative Research Initiatives Center for Adipose Tissue Remodeling, Institute of Molecular Biology and Genetics, Seoul National University)

  • Injae Hwang

    (National Creative Research Initiatives Center for Adipose Tissue Remodeling, Institute of Molecular Biology and Genetics, Seoul National University)

  • Sung Sik Choe

    (National Creative Research Initiatives Center for Adipose Tissue Remodeling, Institute of Molecular Biology and Genetics, Seoul National University)

  • Jeu Park

    (National Creative Research Initiatives Center for Adipose Tissue Remodeling, Institute of Molecular Biology and Genetics, Seoul National University)

  • Yul Ji

    (National Creative Research Initiatives Center for Adipose Tissue Remodeling, Institute of Molecular Biology and Genetics, Seoul National University)

  • Jong In Kim

    (National Creative Research Initiatives Center for Adipose Tissue Remodeling, Institute of Molecular Biology and Genetics, Seoul National University)

  • Gha Young Lee

    (Seoul National University College of Medicine and Seoul National University Bundang Hospital)

  • Sung Hee Choi

    (Seoul National University College of Medicine and Seoul National University Bundang Hospital
    Seoul National University College of Medicine)

  • Jianhong Ching

    (Cardiovascular and Metabolic Disorders, Duke-NUS Medical School)

  • Jean-Paul Kovalik

    (Cardiovascular and Metabolic Disorders, Duke-NUS Medical School)

  • Jae Bum Kim

    (National Creative Research Initiatives Center for Adipose Tissue Remodeling, Institute of Molecular Biology and Genetics, Seoul National University)

Abstract

Obesity is closely associated with increased adipose tissue macrophages (ATMs), which contribute to systemic insulin resistance and altered lipid metabolism by creating a pro-inflammatory environment. Very low-density lipoprotein receptor (VLDLR) is involved in lipoprotein uptake and storage. However, whether lipid uptake via VLDLR in macrophages affects obesity-induced inflammatory responses and insulin resistance is not well understood. Here we show that elevated VLDLR expression in ATMs promotes adipose tissue inflammation and glucose intolerance in obese mice. In macrophages, VLDL treatment upregulates intracellular levels of C16:0 ceramides in a VLDLR-dependent manner, which potentiates pro-inflammatory responses and promotes M1-like macrophage polarization. Adoptive transfer of VLDLR knockout bone marrow to wild-type mice relieves adipose tissue inflammation and improves insulin resistance in diet-induced obese mice. These findings suggest that increased VLDL-VLDLR signaling in ATMs aggravates adipose tissue inflammation and insulin resistance in obesity.

Suggested Citation

  • Kyung Cheul Shin & Injae Hwang & Sung Sik Choe & Jeu Park & Yul Ji & Jong In Kim & Gha Young Lee & Sung Hee Choi & Jianhong Ching & Jean-Paul Kovalik & Jae Bum Kim, 2017. "Macrophage VLDLR mediates obesity-induced insulin resistance with adipose tissue inflammation," Nature Communications, Nature, vol. 8(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-01232-w
    DOI: 10.1038/s41467-017-01232-w
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