leptin
Think of leptin as a fuel gauge that your fat tissue sends to your brain. The more fat you store, the more leptin you release, telling the brain “the tanks are full, you can ease off eating and spend energy freely.” When fat stores shrink, leptin falls, and the brain reads this as a warning to seek food and conserve energy.
Leptin is a peptide hormone made mainly by white adipose tissue, with blood levels roughly proportional to total fat mass. It acts on receptors in the hypothalamus, where it activates appetite-suppressing POMC neurons and inhibits appetite-stimulating AgRP neurons. Through these circuits it reduces food intake and permits energy expenditure, and it also signals to the reproductive, thyroid, and immune systems that enough energy is available.
Despite its role in suppressing appetite, leptin is far more powerful as a starvation signal than as a brake on overeating. A sharp drop in leptin during fasting or weight loss triggers strong hunger and metabolic slowing, whereas chronically high leptin in obesity often fails to curb intake — a state called leptin resistance. Leptin therapy dramatically helps the rare patients with genetic leptin deficiency but does little for common obesity.
Children with rare loss-of-function mutations in the leptin gene develop severe early-onset obesity and constant hunger; daily injections of recombinant leptin normalize their appetite and weight.
Genetic leptin deficiency: a rare proof that leptin is essential for appetite control.
Leptin levels also follow a daily rhythm, peaking at night, and fall quickly with even short-term calorie restriction — which is one reason crash diets feel so hard.