What Is Leptin Signaling?

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  • Written By: Mal Baxter
  • Edited By: Daniel Lindley
  • Last Modified Date: 08 September 2019
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Leptin is a hormone that interacts with the body's energy balance and has the unique property of influencing appetite. The identification in 1994 of this adipose-derived hormone initiated a spate of scientific study of its effects on obesity and diabetes. Produced by fat cells, this hormone is influenced by the activity of leptin receptors in the hypothalamic area of the brain, among other areas. Neurons that influence appetite-regulating neuropeptides have been demonstrated to be influenced by leptin. This neurochemical signaling, regulated by the central nervous system and connecting all the body's systems, also affects numerous other biological processes and behaviors, including immune functions, blood pressure, and bone mass.

The roles of leptin signaling in body processes like cell regulation have generated numerous studies in an attempt to understand the signal pathways and various influences between systems. For example, regulation of fat and muscle cells, pancreatic, and immune cells are additional areas of research in the process of mapping out multiple signal pathways and cross-influences. These include glucose metabolism and insulin regulation, as well as fatty acid metabolism, altered by the leptin signaling within skeletal muscle. The body's self-regulating networks of systems rely on the interaction, or signaling, of neurons with electrochemical potentiation, or electric signals that pass between systems, such as musculoskeletal or digestive, and the brain's executive control.


This hormone distributes through cerebral tissue and crosses the blood brain barrier via unique receptors. It is this area of the brain that divides the brain's extracellular fluid from circulating blood. The barrier regularly transports hormones and other metabolic products through its membrane with specific proteins. An understanding of the delivery of therapeutic agents to specific regions of the brain helps researchers and medical practitioners target areas to prevent sickness and disease, and offers areas of potential research in the treatment of obesity, diabetes, and more.

Located on chromosome seven in humans, leptin signaling affects metabolism and appetite by counteracting the feeding stimulants neuropeptide Y and anandamide, and boosting synthesis of the appetite suppressant alpha melanocyte-stimulating hormone, (α-MSH). An absence of leptin or its receptor reduces the leptin signaling needed to inhibit the intake of food. This results in a diminished sense of fullness, encouraging overeating and leading to obesity.

The presence of human leptin is proportional to the amount of body fat in an individual. This is because it is produced by the adipocytes of white adipose tissue. A protein of 167 amino acids, leptin was discovered through research involving obese mice with mutations in either the leptin encoding gene or its receptor encoding gene.

Behavior has also been demonstrated to affect leptin levels. Studies indicate that fasting and low-calorie diets may lower leptin levels and disrupt optimal leptin signaling. Treatments have shown moderate success using an administration of a recombinant human leptin. Other influencing factors might be stress, sleep deprivation, and hormonal balances, such as a decrease in testosterone and increase in estrogen.


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