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Leptin signalling pathways in hypothalamic neurons

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Abstract

Leptin is the most critical hormone in the homeostatic regulation of energy balance among those so far discovered. Leptin primarily acts on the neurons of the mediobasal part of hypothalamus to regulate food intake, thermogenesis, and the blood glucose level. In the hypothalamic neurons, leptin binding to the long form leptin receptors on the plasma membrane initiates multiple signaling cascades. The signaling pathways known to mediate the actions of leptin include JAK–STAT signaling, PI3K–Akt–FoxO1 signaling, SHP2–ERK signaling, AMPK signaling, and mTOR–S6K signaling. Recent evidence suggests that leptin signaling in hypothalamic neurons is also linked to primary cilia function. On the other hand, signaling molecules/pathways mitigating leptin actions in hypothalamic neurons have been extensively investigated in an effort to treat leptin resistance observed in obesity. These include SOCS3, tyrosine phosphatase PTP1B, and inflammatory signaling pathways such as IKK-NFκB and JNK signaling, and ER stress–mitochondrial signaling. In this review, we discuss leptin signaling pathways in the hypothalamus, with a particular focus on the most recently discovered pathways.

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Acknowledgments

The authors thank Ann W. Kinyua (Wonju College of Medicine, Yonsei University) for critical reading of this manuscript and Dong Ju Yang (Wonju College of Medicine, Yonsei University) for providing the illustrations. This project was supported by Grants from the National Research Foundation (NRF-2013R1A1A1007693 for K.W.K. and 2013M3C7A1056024 for M.S.K.) and the Asan Institute for Life Sciences (Grant No. 13-326) for M.S.K.

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    1. Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea

      Obin Kwon & Min-Seon Kim

    2. Appetite Regulation Laboratory, Asan Institute for Life Science, Seoul, 05505, Korea

      Obin Kwon & Min-Seon Kim

    3. Department of Pharmacology, Yonsei University Wonju College of Medicine, Wonju, 26426, Korea

      Ki Woo Kim

    4. Department of Global Medical Science, Yonsei University Wonju College of Medicine, Wonju, 26426, Korea

      Ki Woo Kim

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    1. Obin Kwon
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    Correspondence to Min-Seon Kim.

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    O. Kwon and K. W. Kim contributed equally to this work.

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    Kwon, O., Kim, K.W. & Kim, MS. Leptin signalling pathways in hypothalamic neurons. Cell. Mol. Life Sci. 73, 1457–1477 (2016). https://doi.org/10.1007/s00018-016-2133-1

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