Leptin and Fragments
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Introduction
Leptin, a protein hormone originating from adipose tissue and a member of the I-type spiral cytokine family, is a product of the obese (ob) gene, which circulates in the plasma and affects the energy balance by interacting with the hypothalamus. Leptin plays an important role in the regulation of a variety of physiological functions, including food intake, body temperature and body weight maintenance, improving the capability of resisting stress and immunity.
Mechanism of action
The biological actions of leptin on target tissues are mediated via several isoforms of receptors, which may differently interact with native leptin and its fragments. The leptin receptor (LR) is a single transmembrane receptor composed of three domains: extracellular, transmembrane and intracellular. According to the amino acid sequence and length of the intracellular domain, LR is divided into two subtypes including growth receptor and short receptor. The LRa and LRb are the most important in the six isoforms of LRa, LRb, LRc, LRd, LRe and LRf that have been found.
The expression of LRb in the hypothalamus is high, and the hypothalamus is considered to be an important site for leptin to act through januskinases (JAK) and activate the signal transducers and activators of transcription (STAT). A series of signal transduction pathways can be activated when leptin binds to the LR to form a dimer, in which the JAK-STAT is primary. The LR itself does not have tyrosine kinase activity, but can be activated and activated after JAK coupling mediates tyrosine kinase autophosphorylation. LRa, LRb, LRc, and LRd share a common N-terminal sequence, including 29 intracellular amino acid sequences that activate JAK-dependent signaling and exert various biological effects in different target cells. Like other cytokine receptors, LRb is activated by mediating autophosphorylation of JAK family tyrosine kinases such as JAK2 and JAK1. Leptin is also involved in the regulation of mitogen-activated protein kinase (MAPK) pathways and the regulation of lipid metabolism and interaction with insulin-induced pathways.
Application of Leptin
Leptin plays an important role in the neuroendocrine and peripheral regulation of energy balance, and is an important signal factor for the regulation of body fat content and regulation of body weight. In human diseases, Leptin plays an important role in the regulation of many diseases, such as obesity, diabetes, Alzheimer's diseases, inflammation and breast cancer and so on. In livestock production, the leptin has significant effects on feeding and growth traits in cattle, sheep and pigs.
References
- Martins, M. N. C., Telles, M. M., Zemdegs, J. C. S., Andrade, I. S., Ribeiro, E. B., & Miranda, A. (2009). Evaluation of new leptin fragments on food intake and body weight of normal rats. Regulatory peptides, 153(1-3), 77-82.
- Malendowicz, L. K., Neri, G., Markowska, A., Hochol, A., Nussdorfer, G. G., & Majchrzak, M. (2003). Effects of leptin and leptin fragments on steroid secretion of freshly dispersed rat adrenocortical cells. The Journal of steroid biochemistry and molecular biology, 87(4-5), 265-268.
- Alipoor, E., Hosseinzadeh, F. M., & Hosseinzadeh-Attar, M. J. (2018). Adipokines in critical illness: A review of the evidence and knowledge gaps. Biomedicine & Pharmacotherapy, 108, 1739-1750.
