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

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Musculoskeletal Disease Associated with Diabetes Mellitus

Abstract

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.

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Authors and Affiliations

  1. Department of Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, 1-4-3, Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan

    Tomoaki Morioka M.D., Ph.D., Katsuhito Mori, Koka Motoyama & Masanori Emoto

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  1. Tomoaki Morioka M.D., Ph.D.
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  2. Katsuhito Mori
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Correspondence to Tomoaki Morioka M.D., Ph.D. .

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  1. Graduate School of Medicine, Osaka City University, Osaka, Osaka, Japan

    Masaaki Inaba

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Morioka, T., Mori, K., Motoyama, K., Emoto, M. (2016). Ectopic Fat Accumulation and Glucose Homeostasis: Role of Leptin in Glucose and Lipid Metabolism and Mass Maintenance in Skeletal Muscle. In: Inaba, M. (eds) Musculoskeletal Disease Associated with Diabetes Mellitus. Springer, Tokyo. https://doi.org/10.1007/978-4-431-55720-3_14

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