Ectopic Fat Accumulation and Glucose Homeostasis: Role of Leptin in Glucose and Lipid Metabolism and Mass Maintenance in Skeletal Muscle

  • Tomoaki MoriokaEmail author
  • Katsuhito Mori
  • Koka Motoyama
  • Masanori Emoto


Skeletal muscle plays a major role in glucose homeostasis. Ectopic lipid accumulation in non-adipose tissue, including skeletal muscle, is an important feature of insulin resistance and type 2 diabetes. Leptin, an adipocyte-derived hormone, regulates glucose and lipid metabolism in skeletal muscle, independent of its central effects on food intake and energy expenditure. While in vitro evidence shows that leptin interacts with insulin signaling to enhance glucose uptake in skeletal muscle, in vivo studies indicate that enhanced insulin sensitivity and glucose uptake induced by leptin in skeletal muscle are mediated by a central mechanism. On the other hand, a direct effect of leptin on skeletal muscle lipid metabolism has been demonstrated in mice. Leptin stimulates mitochondrial fatty acid oxidation by directly activating 5′-AMP-activated protein kinase, through which it depletes the lipid content and reduces lipotoxicity in skeletal muscle. In a mouse model of obesity and diabetes, the regenerative capacity of skeletal muscle is impaired, causing sarcopenia. Evidence from several mouse studies indicates that leptin signaling regulates not only the lipid content of muscle but also muscle mass by inhibiting protein degradation and enhancing myoblast proliferation and differentiation. Thus, impaired leptin action might be a key factor in the negative regulation of skeletal muscle regeneration and the development of sarcopenia in obesity and diabetes. In this chapter, we discuss the current understanding of leptin’s effects on glucose and lipid metabolism in skeletal muscle and on muscle mass maintenance and regeneration in the context of obesity and type 2 diabetes.


Leptin AMPK Intramyocellular lipid Sarcopenia Satellite cell 


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Copyright information

© Springer Japan 2016

Authors and Affiliations

  • Tomoaki Morioka
    • 1
    Email author
  • Katsuhito Mori
    • 1
  • Koka Motoyama
    • 1
  • Masanori Emoto
    • 1
  1. 1.Department of Metabolism, Endocrinology and Molecular MedicineOsaka City University Graduate School of MedicineOsakaJapan

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