Leptin / leptin resistance

Leptin is a 16-kDa adipokine secreted by white adipose tissue in proportion to fat mass; it acts on hypothalamic receptors, particularly in the arcuate nucleus, to suppress appetite via melanocortin signaling and stimulate energy expenditure, functioning as the primary long-term adiposity signal. Plasma leptin levels follow a diurnal pattern and are acutely influenced by insulin; sustained fasting or weight loss reduces leptin, while weight gain raises it over days to weeks. Leptin resistance is a state in which the brain responds inadequately to circulating leptin despite normal or elevated levels, perpetuating hyperphagia and reduced energy expenditure; proposed mechanisms include impaired leptin transport across the blood-brain barrier, receptor downregulation, and disruption of JAK2/STAT3 signaling by inflammatory mediators such as SOCS3. Leptin resistance is present in most obese individuals and is associated with insulin resistance, metabolic syndrome, and impaired recovery of weight-loss-induced leptin deficiency.