In a new study, Yale researchers offer insight into leptin, a hormone that plays a key role in appetite, overeating. Their findings advance knowledge about leptin and cravings, and also suggest a potential strategy for tackling cravings.

The study, led by investigators at Yale and Harvard, was published the week of June 17, 2019, in the journal PNAS.

Leptin, which is secreted by fat cells, informs the brain when fuel stored in body fat and in the liver is becoming depleted. It has not been well understood how low leptin concentrations in plasma—the largest component of blood—increase appetite. The researchers studied the biology of leptin in rodents. They also investigated the influence of nerve cells in the brain known as AgRP neurons, which regulate eating behavior.

The researchers discovered that the mechanisms by which reductions in plasma leptin concentrations stimulate food intake are not limited to the brain, as previously thought. In rodents, fasting first activates leptin receptors in the brain, followed by an intermediary step that involves the endocrine system. This system includes the pituitary and adrenal glands, which secrete another hormone, corticosterone, that regulates energy, stress responses.

The research team learned that this chain of events is required for leptin to stimulate hunger when food is restricted, or when diabetes is poorly controlled and plasma leptin concentrations drop below a critical threshold, said Gerald Shulman, M.D., the George R. Cowgill Professor of Medicine at Yale School of Medicine, and co-corresponding author of the study.