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Cell. Mol. Life Sci., April 2016, Volume 73, Issue 7, pp 1457-1477 | https://doi.org/10.1007/s00018-016-2133-1
Leptin signalling pathways in hypothalamic neurons
Obin Kwon1,2, Ki Woo Kim3,4, Min-Seon Kim1,2,*
1Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
1Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
2Appetite Regulation Laboratory, Asan Institute for Life Science, Seoul, Korea
3Department of Pharmacology, Yonsei University Wonju College of Medicine, Wonju, Korea
4Department of Global Medical Science, Yonsei University Wonju College of Medicine, Wonju, Korea
O. Kwon and K. W. Kim contributed equally to this work.
*To whom correspondence may be addressed.
O. Kwon and K. W. Kim contributed equally to this work.
*To whom correspondence may be addressed.
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
논문정보
- Review Paper
- 2016년 04월 (BRIC 등록일 2018-09-21)
- 국내 연구진
- 의약학 > 응용의학
- 60회 이상 인용된 논문
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