Leptin

Leptin is a hormone that is produced in fat cells and functions to regulate body weight and eating. It was the first hormone discovered within fat cells and is part of the class of hormones now known as adipokines (hormones produced in the fat). Other hormones made in fat cells include adiponectin and resistin. In the mid-1950s, a mouse was discovered at Jackson Laboratories that ate a large amount of food and performed very little physical activity and became very obese. The gene required for the mouse to become obese was known as the ob gene. Mice that had two ob genes were the only mice to become obese and subsequently these animals were named the ob/ob [Page 426]mice. Leptin was discovered in the mid-1990s as the hormone that was responsible for the obesity observed in the ob/ob mouse. The word leptin comes from the Greek word lepthos, which means thin.

Leptin was originally hypothesized to regulate how much food a person eats and how much physical activity he or she performs. The ob/ob mouse was very obese and had no leptin in its body. Once these leptin-deficient mice were given an infusion of leptin, they stopped eating and lost their extra body weight. It was later determined that when a normal mouse (not the ob/ob mouse) had a large amount of adipose tissue (fat cells), then it would have high levels of leptin. When leptin levels are high, the animals' appetite would decrease (they would eat less food), and the amount of physical activity they use would increase (they would move more in their cages). Alternatively, when leptin levels are low (in a thin animal), the animals' appetite would increase (they would eat more food) and the amount of physical activity they use would decrease (they would move less in their cages).

Leptin is believed to travel from fat cells to the brain. A leptin receptor is located on the brain which helps move leptin across the blood–brain barrier. Once in the brain, leptin is able to regulate if a person is hungry or if he or she satiated. Leptin works in the hypothalamus region of the brain and affects neuropeptide Y pathway, agouti related protein (AGRP) pathway, and the pro-opiomelanocortin (POMC) pathway as well as other pathways. Originally, leptin was believed to only be produced in fat cells, but small amounts of leptin are produced in other tissues as well such as the stomach, intestines, and the brain.

Once leptin was discovered in 1994, it was hypothesized that people who were overweight or obese must have had very low levels of this hormone and that is why people who are overweight or obese eat so much. Many biotechnology and pharmaceutical companies were interested in making a synthetic leptin as a treatment to control body weight. However, the opposite hypothesis was observed. People who were obese or overweight had more leptin than people who were thin. It was then proposed that overweight and obese people might be leptin resistant, that is their tissues were no longer responsive to the actions of leptin. Another proposed hypothesis was that leptin primarily works when people do not eat. When a person does not eat a sufficient amount of food, they may enter a starvation-like state. During these starvation conditions, the leptin begins to work and tells the body that it needs to eat.

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