Role of Hormone-sensitive Lipase in Leptin-Promoted Fat Loss and Glucose Lowering

Access this Article

Search this Article

Author(s)

    • Takanashi Mikio
    • Departments of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo
    • Kumagai Hidetoshi
    • Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo
    • Ikeda Yuichi
    • Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo
    • Iizuka Yoko
    • Departments of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo
    • Yahagi Naoya
    • Departments of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo
    • Shimano Hitoshi
    • Departments of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo
    • Osuga Jun-ichi
    • Division of Endocrinology and Metabolism, Department of Medicine, Jichi Medical University
    • Ishibashi Shun
    • Division of Endocrinology and Metabolism, Department of Medicine, Jichi Medical University
    • Kadowaki Takashi
    • Departments of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo
    • Okazaki Hiroaki
    • Departments of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo
    • Taira Yoshino
    • Departments of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo
    • Okazaki Sachiko
    • Departments of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo
    • Takase Satoru
    • Departments of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo
    • Kimura Takeshi
    • Departments of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo
    • Li Cheng Cheng
    • Departments of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo
    • Xu Peng Fei
    • Departments of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo
    • Noda Akari
    • Departments of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo
    • Sakata Ichiro
    • Area of Regulatory Biology, Division of Life Science, Graduate School of Science and Engineering, Saitama University

Abstract

<p><b><i>Aim</i></b><b>: </b>Myriad biological effects of leptin may lead to broad therapeutic applications for various metabolic diseases, including diabetes and its complications; however, in contrast to its anorexic effect, the molecular mechanisms underlying adipopenic and glucose-lowering effects of leptin have not been fully understood. Here we aim to clarify the role of hormone-sensitive lipase (HSL) in leptin's action.</p><p><b><i>Methods</i></b><b>: </b>Wild-type (WT) and HSL-deficient (HSLKO) mice were made hyperleptinemic by two commonly-used methods: adenovirus-mediated overexpression of leptin and continuous subcutaneous infusion of leptin by osmotic pumps. The amount of food intake, body weights, organ weights, and parameters of glucose and lipid metabolism were measured.</p><p><b><i>Results</i></b><b>: </b>Hyperleptinemia equally suppressed the food intake in WT and HSLKO mice. On the other hand, leptin-mediated fat loss and glucose-lowering were significantly blunted in the absence of HSL when leptin was overexpressed by recombinant adenovirus carrying leptin. By osmotic pumps, the fat-losing and glucose-lowering effects of leptin were milder due to lower levels of hyperleptinemia; although the difference between WT and HSLKO mice did not reach statistical significance, HSLKO mice had a tendency to retain more fat than WT mice in the face of hyperleptinemia.</p><p><b><i>Conclusions</i></b><b>: </b>We clarify for the first time the role of HSL in leptin's effect using a genetic model: leptin-promoted fat loss and glucose-lowering are at least in part mediated via HSL-mediated lipolysis. Further studies to define the pathophysiological role of adipocyte lipases in leptin action may lead to a new therapeutic approach to circumvent leptin resistance.</p>

Journal

  • Journal of Atherosclerosis and Thrombosis

    Journal of Atherosclerosis and Thrombosis 24(11), 1105-1116, 2017

    Japan Atherosclerosis Society

Codes

  • NII Article ID (NAID)
    130006191603
  • Text Lang
    ENG
  • ISSN
    1340-3478
  • Data Source
    J-STAGE 
Page Top