The discovery of leptin hormone in 1994 heralded a new dawn in the medical world, and specifically in the understanding of obesity. Leptin hormone plays a critical role in that it regulates energy balance in the body, thus affecting obesity. Over the last two decades, scientists have made significant discoveries on the various roles that the hormone plays in the body. This paper provides an in-depth review of the leptin hormone and the roles that it plays in the body.
Leptin belongs in the category of adipocyte hormones. Leptin secretion occurs in response to lipid storage in the body (Takanashi et al., 2017). The major role of leptin is in regulating energy metabolism in the body. It achieves this role through three mechanisms, which primarily involve acting in the brain. First, leptin inhibits food intake. Second, leptin stimulates the breakdown of lipids in the adipose tissue, a process known as lipolysis. Third, leptin enhances peripheral insulin sensitivity, which is how peripheral tissues such as muscle and others can absorb fat (Takanashi et al., 2017). These three effects are very critical in the human body and in development of medicines. It is because of the three mechanisms that leptin is currently applied in managing various pathogenic conditions, including diabetes and obesity. Leptin is effective in improving glucose metabolism in the body. It is vital in managing the complications that arise from diabetes and obesity.
Leptin hormone acts through the brain or central nervous system (CNS). Leptin has significant impacts on synaptic plasticity (strengthening and weakening of synapses) in the arcuate nucleus of the hypothalamus (Elmquist & Flier, 2004). Leptin hormone targets the articulate nucleus of the hypothalamus. The arcuate nucleus comprises of a group of neurons in the hypothalamus that help in mediating different physiological and neuroendocrine functions. The articular nucleus has two different groups of neurons. These groups of neurons have a different influence on food intake. The first group of neurons induces appetite through production of neuropeptides NPY and agouti-related protein (AgRP) (Elmquist & Flier, 2004). The neuropeptide and the agouti protein stimulate appetite. The second group comprises of appetite-inhibiting neurons. These neurons produce neuropeptides POMC and a protein known as cocaine-and amphetamine-regulated transcript (CART). Both groups of neurons have leptin receptors, but they act in opposite ways.
Leptin has a direct action on the POMC/CART activation, which in turn blocks the NPY/AgRP neurons. In addition, NPY/AgRP produces a neurotransmitter known as GABA that acts as an inhibitor (Takanashi et al., 2017). This neurotransmitter sends messages to POMC/CART resulting to their inhibition. In situations where an individual suffers from inadequate levels of leptin, the inhibitory actions to the POMC/CART and NPY/AgRP are compromised (Elmquist & Flier, 2004). This inhibits the appetite suppression process, leading to increased food intake levels in the individual. Inadequate levels of leptin thus leads to high excitatory effect on the NPY/AgRP neurons and less excitatory effect on the POMC/CART neurons. Studies indicate that repletion of leptin hormone in mice reverses these effects (Šabovič & Mavri, 2016). This is a clear indication that leptin hormone has a great potential in the management of diabetes and obesity in humans.
The following diagram shows leptin’s interaction with the brain leading to energy balance in the body.
It is possible to see that leptin has a direct action on the arcuate nucleus neurons by binding on the receptors. Leptin affects the neurons in different ways, thus controlling appetite. Presence of leptin activates the POMC, while inhibiting the NPY.
Elmquist, J. K., & Flier, J. S. (2004). Neuroscience. The fat-brain axis enters a new dimension. Science (New York, N.Y.), 304(5667), 63-64. doi:10.1126/science.1096746
Šabovič, M., & Mavri, A. (2016). leptin and obesity – neuroendocrine , metabolic and atherogenic effects of leptin. Zdravniški Vestnik, 72(1)
Takanashi, M., Taira, Y., Okazaki, S., Takase, S., Kimura, T., Li, C. C., . . . Okazaki, H. (2017). Role of hormone-sensitive lipase in leptin-promoted fat loss and glucose lowering. Journal of Atherosclerosis and Thrombosis, doi:10.5551/jat.39552