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The Regulation of Appetite by Leptin in Humans

Leptin, a hormone predominantly synthesized and secreted by adipocytes, plays a pivotal role in the intricate orchestration of energy homeostasis within the human body. Leptin’s influence extends beyond mere appetite suppression, impacting a diverse array of physiological processes, including metabolism, reproduction, immune function, and even cardiovascular physiology (Frühbeck, 2005). The primary mechanism through which leptin exerts its anorectic effects involves modulation of hypothalamic neural circuits (Jang et al., 2021). Leptin traverses the blood-brain barrier to engage with specific receptors located on neurons within the arcuate nucleus of the hypothalamus (Hegyi et al., 2004). Upon binding, leptin activates intracellular signaling cascades, most notably the Janus kinase-signal transducer and activator of transcription pathway, leading to the phosphorylation and activation of STAT3 (Francisco et al., 2018). This transcription factor then translocates to the nucleus, where it modulates the expression of target genes involved in energy balance (Yoon et al., 2000).

The arcuate nucleus houses two distinct neuronal populations that are critically important for leptin’s effects on appetite: the orexigenic neurons that produce neuropeptide Y and agouti-related peptide, and the anorexigenic neurons that synthesize pro-opiomelanocortin and cocaine- and amphetamine-regulated transcript. Leptin stimulates the activity of the anorexigenic neurons, leading to increased production of α-melanocyte-stimulating hormone, which then binds to melanocortin receptors in the paraventricular nucleus of the hypothalamus, ultimately resulting in

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References

Francisco, V., Pino, J., Campos-Cabaleiro, V., Ruiz‐Fernández, C., Mera, A., González‐Gay, M. Á., Gómez, R., & Gualillo, O. (2018). Obesity, Fat Mass and Immune System: Role for Leptin [Review of Obesity, Fat Mass and Immune System: Role for Leptin]. Frontiers in Physiology, 9. Frontiers Media. https://doi.org/10.3389/fphys.2018.00640

Frühbeck, G. (2005). Intracellular signalling pathways activated by leptin [Review of Intracellular signalling pathways activated by leptin]. Biochemical Journal, 393(1), 7. Portland Press. https://doi.org/10.1042/bj20051578

Hegyi, K., Fülöp, A., Kovács, K., Tóth, S., & Falus, A. (2004). Leptin‐induced signal transduction pathways [Review of Leptin‐induced signal transduction pathways]. Cell Biology International, 28(3), 159. Wiley. https://doi.org/10.1016/j.cellbi.2003.12.003

Jang, Y., Heo, J. Y., Lee, M. Y., Zhu, J., Seo, C., Go, D., Yoon, S. W., Date, Y., Oike, Y., Sohn, J., Shong, M., & Kweon, G. R. (2021). Angiopoietin-Like Growth Factor Involved in Leptin Signaling in the Hypothalamus. International Journal of Molecular Sciences, 22(7), 3443. https://doi.org/10.3390/ijms22073443

Yoon, J. C., Chickering, T. W., Rosen, E. D., Dussault, B. J., Qin, Y., Soukas, A. A., Friedman, J. M., Holmes, W. E., & Spiegelman, B. M. (2000). Peroxisome Proliferator-Activated Receptor γ Target Gene Encoding a Novel Angiopoietin-Related Protein Associated with Adipose Differentiation. Molecular and Cellular Biology, 20(14), 5343. https://doi.org/10.1128/mcb.20.14.5343-5349.2000