Leptin

Leptin is a peptide hormone, a product of the obese (ob) gene, that is synthesized and secreted from fat cells in white adipose tissue and regulates food intake, body mass, and reproductive function. ^[1] The discovery of leptin changed the view of adipose tissue from a passive fat store to a dynamic endocrine organ that actively regulates behaviour and metabolism. ^[2]

Leptin binds to and activates its cognate leptin receptor and regulates body mass via a negative feedback mechanism between adipose tissue and the hypothalamus. ^[1] Leptin functions as an afferent signal in a negative feedback loop, acting primarily on neurons in the hypothalamus to regulate feeding and many other functions, and also serves as a mediator of the adaptation to fasting. ^{[2] [3]} Leptin must cross the blood-brain barrier to reach the hypothalamus and exert its anorexigenic functions. ^[4] Leptin and adiponectin are adipose-derived hormones whose levels diverge in obesity, with hyperleptinemia accompanying hypoadiponectinemia, and reviews propose raising the adiponectin-to-leptin ratio to prevent or reverse obesity-associated cardiovascular disorders ^[5] Leptin is among the adipokines secreted by dysfunctional visceral fat and released into portal blood, a flux that inundates the liver and promotes insulin resistance in the setting of adipose inflammation ^[6] Leptin is one of the adipokines orchestrating obesity-associated metabolic inflammation, an immune response that promotes insulin resistance along with metabolic dysfunction-associated liver disease and cardiovascular complications ^[7] Cold exposure, like fasting, leads to sympathetic stimulation of white adipose tissue and thereby decreases leptin gene expression and leptin production, whereas sympathetic blockade often raises circulating leptin ^[8]