Leptin is a 16 kDa protein hormone that plays a key role in regulating energy intake and energy expenditure (appetite and metabolism).
Leptin was discovered in 1994 in mice by Jeffrey M. Friedman and team at the Rockefeller University. The Ob(Lep) gene is located on the 7th chromosome in humans. Leptin is produced by adipose tissue and interacts with six types of receptor (LepRa to LepRf). LepRb is the only receptor isoform that contains active intracellular signaling domains. This receptor is present in a number of hypothalamic nuclei, where it exerts its effects. Leptin was cloned by studying mutant obese mice that arose at random within a mouse colony at the Jackson Laboratory in 1950. These mice were massively obese and hyperphagic. A very small group of humans, mostly arising from inbred populations, are also mutant for the leptin gene. These people eat nearly constantly, and may be more than 100 pounds (45 kg) overweight by the age of 7.
Leptin is released by fat cells in amounts mirroring overall body fat stores. Thus, circulating leptin levels give the brain a reading of energy storage for the purposes of regulating appetite and metabolism. Leptin works by inhibiting the activity of neurons that contain neuropeptide Y (NPY) and agouti-related peptide (AgRP), and by increasing the activity of neurons expressing alpha-melanocortin-stimulating hormone (α-MSH). The NPY neurons are a key element in the regulation of appetite; small doses of NPY injected into the brains of experimental animals stimulates feeding, while selective destruction of the NPY neurons in mice causes them to become anorexic. Conversely, α-MSH is an important mediator of satiety, and differences in the gene for the receptor at which α-MSH acts in the brain are linked to obesity in humans.
Leptin is also regulated (downward) by melatonin during the night. PMID 15311999
Leptin as adiposity signal
To date, only leptin and insulin fulfill the criteria of an adiposity signal:
