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Cellular and Molecular Life Sciences

, Volume 73, Issue 7, pp 1457–1477 | Cite as

Leptin signalling pathways in hypothalamic neurons

  • Obin Kwon
  • Ki Woo Kim
  • Min-Seon KimEmail author
Review

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.

Keywords

Leptin Signaling Hypothalamus Neurons Obesity Cilia 

Notes

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.

Compliance with ethical standards

Conflict of interest

The authors declare no conflicts of interest.

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Copyright information

© Springer International Publishing 2016

Authors and Affiliations

  1. 1.Division of Endocrinology and Metabolism, Asan Medical CenterUniversity of Ulsan College of MedicineSeoulKorea
  2. 2.Appetite Regulation LaboratoryAsan Institute for Life ScienceSeoulKorea
  3. 3.Department of PharmacologyYonsei University Wonju College of MedicineWonjuKorea
  4. 4.Department of Global Medical ScienceYonsei University Wonju College of MedicineWonjuKorea

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