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Adiponectin, a unique adipocyte-derived factor beyond hormones

  • Norikazu Maeda
    Correspondence
    Corresponding author. Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, 2-2, Yamada-oka, Suita, Osaka, 565-0871, Japan.
    Affiliations
    Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, 2-2, Yamada-oka, Suita, Osaka, 565-0871, Japan

    Department of Metabolism and Atherosclerosis, Graduate School of Medicine, Osaka University, 2-2, Yamada-oka, Suita, Osaka, 565-0871, Japan
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  • Tohru Funahashi
    Affiliations
    Division of Osaka Health Support Center, Sumitomo Mitsui Banking Corporation, 6-5, Kitahama 4-chome, Chuo-ku, Osaka, Osaka, 541-0041, Japan
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  • Yuji Matsuzawa
    Affiliations
    Department of Endocrinology and Metabolism, Sumitomo Hospital, 5-3-20, Nakanoshima, Kita-ku, Osaka, Osaka, 530-0005, Japan
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  • Iichiro Shimomura
    Affiliations
    Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, 2-2, Yamada-oka, Suita, Osaka, 565-0871, Japan
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      Highlights

      • Adiponectin acts as a central player to prevent and protect from metabolic syndrome.
      • Adiponectin enhances exosome biogenesis through T-cadherin.
      • Adiponectin/T-cadherin system plays a crucial role in cardiovascular protection.

      Abstract

      Visceral fat accumulation has a marked impact on atherosclerotic cardiovascular diseases and metabolic syndrome clustering diabetes, dyslipidemia, and hypertension. Adiponectin, an adipocyte-derived circulating protein, is a representative adipocytokine and uniquely possesses two major properties: 1) its circulating concentration is approximately 3–6 orders of magnitude greater than ordinary hormones and cytokines; 2) its concentration inversely correlates with body fat mass despite its adipocyte-specific production. Low serum levels of adiponectin correlate with cardiometabolic diseases. Extensive experimental evidence has demonstrated that adiponectin possesses multiple properties, such as anti-atherosclerotic, anti-diabetic, and anti-inflammatory activities. It has been shown to play a central role against the development of metabolic syndrome and its complications. However, even approximately 25 years after its discovery, the properties of adiponectin, including how and why it exerts multiple beneficial effects on various tissues and/or organs, remain unclear. Furthermore, the mechanisms responsible for the very high circulating concentrations of adiponectin in the bloodstream have not been elucidated. Several adiponectin-binding partners, such as AdipoR1/2, have been identified, but do not fully explain the multi-functional and beneficial properties of adiponectin. Recent advances in adiponectin research may resolve these issues. Adiponectin binds to and covers cell surfaces with T-cadherin, a unique glycosylphosphatidylinositol (GPI)-anchored cadherin. The adiponectin/T-cadherin complex enhances exosomal production and release, excreting cell-toxic products from cells, particularly in the vasculature. In this review, we discuss adiponectin and the role of the adiponectin/T-cadherin system in the maintenance of whole body homeostasis and cardiovascular protection.

      Keywords

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