Long-term satiety signals

Despite day-to-day imbalances between food intake and energy expenditure, people are able to match energy input and output closely over years. This is done largely by defending the size of the body store of white adipose tissue in Figure.

Leptin is secreted by fat cells and crosses the blood–brain barrier to act at the hypothalamus where it inhibits feeding (i.e., it is a satiety factor) and increases energy expenditure. Leptin acts as an adipostat. It has a plasma concentration that correlates well with body fat content and so is a molecule that reflects the size of the fat store and regulates it homeostatically. Leptin secretion is enhanced by the insulin-stimulated lipogenesis that occurs on feeding and is suppressed by the glucocorticoid-stimulated lipolysis which accompanies fasting so leptin regulates fat mass through means of a negative feedback loop.

Leptin raises energy expenditure by increasing the expression of uncoupling proteins in mitochondria of fat and skeletal muscle, and by acting centrally to increase sympathetic activity to brown adipose tissue. Both effects raise basal metabolic rate. Insulin is also a long-term satiety signal.