Leptin

Author: Prof. Dr. med. Peter Altmeyer

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Last updated on: 17.05.2021

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Synonym(s)

Long-chain helical cytokine

Definition
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Leptin belongs to the long-chain helical cytokine family (Matarese G 2000). Leptin is expressed by adipose tissue, gastric epithelium and brain cells (Bado A et al. 1998). In the hypothalamus, leptin stimulates metabolic rate and has appetite inhibitory effects. Leptin has regulatory functions in angiogenesis, homeostasis, hematopoiesis, thermogenesis, and chondrogenesis. Leptin also influences neuroendocrine and immunological processes (Fantuzzi G et al. 2000). For example, leptin acts by acting as a proinflammatory cytokine in monocytes and lymphocytes, thereby promoting the production of Th1-type cytokines.

Furthermore, leptin influences reproductive processes. During pregnancy, the maternal leptin concentration increases and decreases again after birth. Leptin influences the course of pregnancy by regulating ovarian function and maturation and embryonic development (Cervero A et al. 2004). In addition, leptin promotes trophoblast proliferation, fetal growth, and lactation.In osteoblasts, monocytes, eosinophilic granulocytes, and other cells, leptin has anti-apoptotic effects (Conus S et al 2005).

Leptin is a ligand of the leptin receptor (ObR, LEPR). The leptin receptor belongs to the gp130 family of cytokine receptors (Tartaglia LA et al 1995). Through its cytosolic domain, the leptin receptor is associated with tyrosine kinases. It has no tyrosine kinase activity of its own. Alternative splicing gives rise to the 6 leptin receptor isoforms: ObRa, ObRb, ObRc, ObRd, ObRe and ObRf (Harvey J et al 2003).

Leptin itself is a target gene of the nuclear receptor PPARγ and thus also a target gene of RXRα, the heterodimeric partner of PPARγ. RXRα and PPARγ are also likely involved in the regulation of leptin in the placenta. RXR agonists are able to regulate leptin expression and thereby positively influence pregnancy outcome. Furthermore, leptin influences reproductive processes. During pregnancy the maternal leptin concentration increases and decreases after birth. Leptin influences the course of pregnancy by regulating the function and maturation of the ovaries and the development of the embryo (Cervero A et al. 2004).

In addition, leptin promotes trophoblast proliferation, fetal growth and lactation, and has anti-apoptotic effects in osteoblasts, monocytes, eosinophil granulocytes and other cells (Conus S et al. 2005).

Literature
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  1. Bado A et al (1998) The stomach is a source of leptin. Nature 394: 790-793.
  2. Cervero A et al (2004) The leptin system during human endometrial receptivity and preimplantation development. J Clin Endocrinol Metab 89:2442-2451.
  3. Conus S et al (2005) Leptin is an eosinophilic survival factor. J Allergy Clin Immunol 116:1228-1234.
  4. Fantuzzi G et al (2000) Leptin in the regulation of immunity, inflammation, and hematopoiesis. J Leukoc Biol 68: 437-46.
  5. Harvey J et al (2003) Leptin in the CNS: much more than a satiety signal. Neuropharmacology 44: 845-854.
  6. Matarese G (2000) Leptin and the immune system: how nutritional status influences the immune response. Eur Cytokines Netw 11: 7-14.
  7. Schwartz MW et al (2000) Central nervous system control of food intake. Nature 404: 661-671.
  8. Takaya K et al.(1996) Molecular cloning of rat leptin receptor isoform complementary DNAs--identification of a missense mutation in sugar fatty (fa/fa) rat. Biochem Biophys Res Commun 225: 75-83.
  9. Tartaglia LA et al (1995) Identification and expression cloning of a leptin receptor, OB-R. Cell 83: 1263-1271.
  10. Yamashita H et al (2001) Leptin administration prevents spontaneous gestational diabetes in heterozygous Lepr(db/+) mice: effects on placental leptin and fetal growth. Endocrinology 142: 2888-2897.

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Last updated on: 17.05.2021