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Cell Mol Life Sci. 2016 Apr;73(7):1457-77. doi: 10.1007/s00018-016-2133-1. Epub 2016 Jan 19.

Leptin signalling pathways in hypothalamic neurons.

Kwon O1,2, Kim KW3,4, Kim MS5,6.

Author information

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.
2
Appetite Regulation Laboratory, Asan Institute for Life Science, Seoul, 05505, Korea.
3
Department of Pharmacology, Yonsei University Wonju College of Medicine, Wonju, 26426, Korea.
4
Department of Global Medical Science, Yonsei University Wonju College of Medicine, Wonju, 26426, Korea.
5
Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea. mskim@amc.seoul.kr.
6
Appetite Regulation Laboratory, Asan Institute for Life Science, Seoul, 05505, Korea. mskim@amc.seoul.kr.

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:

Cilia; Hypothalamus; Leptin; Neurons; Obesity; Signaling

PMID:
26786898
DOI:
10.1007/s00018-016-2133-1
[Indexed for MEDLINE]

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