Neuropeptide Y resists excess loss of fat by lipolysis in calorie-restricted mice: a trait potential for the life-extending effect of calorie restriction

Authors

  • Seongjoon Park,

    Corresponding author
    1. Department of Pathology, Nagasaki University School of Medicine, Graduate School of Biomedical Sciences, Nagasaki, Japan
    • Correspondence

      Seongjoon Park, Department of Pathology, Nagasaki University School of Medicine, Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan. Tel.: +81 95 849 7051; fax: +81 95 849 7052; e-mail: psj1026@nagasaki-u.ac.jp

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  • Toshimitsu Komatsu,

    1. Department of Pathology, Nagasaki University School of Medicine, Graduate School of Biomedical Sciences, Nagasaki, Japan
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  • Sang Eun Kim,

    1. Department of Pathology, Nagasaki University School of Medicine, Graduate School of Biomedical Sciences, Nagasaki, Japan
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  • Katsuya Tanaka,

    1. Department of Pathology, Nagasaki University School of Medicine, Graduate School of Biomedical Sciences, Nagasaki, Japan
    2. Department of Plastic and Reconstructive Surgery, Nagasaki University School of Medicine, Graduate School of Biomedical Sciences, Nagasaki, Japan
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  • Hiroko Hayashi,

    1. Department of Pathology, Nagasaki University School of Medicine, Graduate School of Biomedical Sciences, Nagasaki, Japan
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  • Ryoichi Mori,

    1. Department of Pathology, Nagasaki University School of Medicine, Graduate School of Biomedical Sciences, Nagasaki, Japan
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  • Isao Shimokawa

    1. Department of Pathology, Nagasaki University School of Medicine, Graduate School of Biomedical Sciences, Nagasaki, Japan
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Summary

Neuropeptide Y (NPY) is an orexigenic peptide that plays an essential role in caloric restriction (CR)-mediated lifespan extension. However, the mechanisms underlying the NPY-mediated effects in CR are poorly defined. Here, we report that NPY deficiency in male mice during CR increases mortality in association with lipodystrophy. NPY−/− mice displayed a rapid decrease in body weight and fat mass, as well as increased lipolysis during CR. These alterations in fat regulation were inhibited by the lipolysis inhibitor, acipimox, a treatment associated with reduced mortality. The lipolytic/thermogenic signaling, β3-adrenergic receptor/hormone sensitive lipase, was markedly activated in white adipose tissue of NPY−/− mice compared with that of NPY+/+ mice, and thermogenesis was controlled by NPY under negative energy balance. These results demonstrate the critical role of NPY in the regulation of lipid metabolic homeostasis and survival via control of lipolysis and thermogenesis in a state of negative energy balance.

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