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Clusterin and LRP2 are critical components of the hypothalamic feeding regulatory pathway

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  • So Young Gil

    (Asan Institute for Life Science, University of Ulsan College of Medicine)

  • Byung-Soo Youn

    (AdipoGen Inc.)

  • Kyunghee Byun

    (Lee Gil Ya Cancer and Diabetes Institute, Gachon University
    Gachon Medical Research Institute, Gachon University Gil Medical Center)

  • Hu Huang

    (Diabetes and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School)

  • Churl Namkoong

    (Asan Institute for Life Science, University of Ulsan College of Medicine)

  • Pil-Geum Jang

    (Asan Institute for Life Science, University of Ulsan College of Medicine)

  • Joo-Yong Lee

    (Asan Institute for Life Science, University of Ulsan College of Medicine)

  • Young-Hwan Jo

    (Albert Einstein College of Medicine)

  • Gil Myoung Kang

    (Asan Institute for Life Science, University of Ulsan College of Medicine)

  • Hyun-Kyong Kim

    (Asan Institute for Life Science, University of Ulsan College of Medicine)

  • Mi-Seon Shin

    (Asan Medical Center, University of Ulsan College of Medicine)

  • Claus U. Pietrzik

    (Institute of Pathobiochemistry, University Medical Center of the Johannes Gutenberg-University Mainz)

  • Bonghee Lee

    (Lee Gil Ya Cancer and Diabetes Institute, Gachon University
    Gachon Medical Research Institute, Gachon University Gil Medical Center)

  • Young-Bum Kim

    (Lee Gil Ya Cancer and Diabetes Institute, Gachon University
    Diabetes and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School)

  • Min-Seon Kim

    (Asan Institute for Life Science, University of Ulsan College of Medicine
    Asan Medical Center, University of Ulsan College of Medicine)

Abstract

Hypothalamic feeding circuits are essential for the maintenance of energy balance. There have been intensive efforts to discover new biological molecules involved in these pathways. Here we report that central administration of clusterin, also called apolipoprotein J, causes anorexia, weight loss and activation of hypothalamic signal transduction-activated transcript-3 in mice. In contrast, inhibition of hypothalamic clusterin action results in increased food intake and body weight, leading to adiposity. These effects are likely mediated through the mutual actions of the low-density lipoprotein receptor-related protein-2, a potential receptor for clusterin, and the long-form leptin receptor. In response to clusterin, the low-density lipoprotein receptor-related protein-2 binding to long-form leptin receptor is greatly enhanced in cultured neuronal cells. Furthermore, long-form leptin receptor deficiency or hypothalamic low-density lipoprotein receptor-related protein-2 suppression in mice leads to impaired hypothalamic clusterin signalling and actions. Our study identifies the hypothalamic clusterin–low-density lipoprotein receptor-related protein-2 axis as a novel anorexigenic signalling pathway that is tightly coupled with long-form leptin receptor-mediated signalling.

Suggested Citation

  • So Young Gil & Byung-Soo Youn & Kyunghee Byun & Hu Huang & Churl Namkoong & Pil-Geum Jang & Joo-Yong Lee & Young-Hwan Jo & Gil Myoung Kang & Hyun-Kyong Kim & Mi-Seon Shin & Claus U. Pietrzik & Bonghee, 2013. "Clusterin and LRP2 are critical components of the hypothalamic feeding regulatory pathway," Nature Communications, Nature, vol. 4(1), pages 1-10, October.
  • Handle: RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms2896
    DOI: 10.1038/ncomms2896
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    Cited by:

    1. Chen Chen & Yaqing Shu & Chengkai Yan & Huilu Li & Zhenchao Huang & ShiShi Shen & Chunxin Liu & Yanjun Jiang & Shixiong Huang & Zhanhang Wang & Feng Mei & Feng Qin & Xiaodong Liu & Wei Qiu, 2024. "Astrocyte-derived clusterin disrupts glial physiology to obstruct remyelination in mouse models of demyelinating diseases," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

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