Leptin, a hormone that plays an outsized role in appetite, overeating and obesity, isn’t alone in regulating our hunger or distaste for food.

Leptin regulates food intake and body weight by modulating the size of the adipose tissues -- better known as fat -- in the body.

The adipose tissues’ main role is to store energy in the form of fat, but it also cushions and insulates the body. Regulating fat stores is the primary function of leptin, which also plays a role in other physiological processes associated with hunger and satiety.

Secreted by fat cells, leptin informs the brain when fuel stored in body fat and in the liver is becoming depleted.

Leptin works on the human body in this way. When fat mass decreases, the level of plasma leptin. This drop stimulates the appetite until the fat mass is recovered. On the other hand, when fat mass increases, leptin levels also increase and appetite is suppressed until weight loss occurs.

Leptin also plays a crucial role in regulating and modulating the onset of puberty.

Now, a new study into leptin shows the hormone isn’t alone in acting the way it does.

Researchers from Yale University and Harvard University offer more insights into leptin in a new study published this week in the Proceedings of the National Academy of Sciences.

The study increases our knowledge about leptin and weight gain, and also points towards a potential strategy for developing future weight-loss treatments.

The study gives us a better understanding of how low leptin concentrations in blood plasma increase appetite. Researchers discovered that the mechanisms by which reductions in plasma leptin concentrations stimulate food intake aren’t limited to the brain, as previously thought.

In rodents, fasting first activates leptin receptors in the brain, followed by an intermediary step involving the endocrine system. This system includes the pituitary and adrenal glands. It secretes another hormone -- corticosterone -- that regulates energy, stress responses, and food intake

The study shows this chain of events is required for leptin to stimulate hunger when food is restricted, said Dr. Gerald Shulman, M.D., the George R. Cowgill Professor of Medicine at Yale School of Medicine, and co-corresponding author of the study.

This chain of events is also required when diabetes is poorly controlled and plasma leptin concentrations drop below a critical threshold.

Researchers also discovered that plasma corticosterone activates the AgRP neurons that increase hunger when either leptin or blood-sugar levels are low. Leptin and blood sugar drop when people diet.

In sum, the study reveals "the basic biology of leptin, and how the endocrine system is mediating its effect to regulate food intake under conditions of starvation and poorly controlled diabetes," said Dr. Shulman.

Other study authors are Rachel J. Perry, Jon M. Resch, Amelia M. Douglass, Joseph C. Madara, Aviva Rabin-Court, Hakan Kucukdereli, Chen Wu, Joongyu D. Song, and Bradford B. Lowell. The study was funded by grants from the U.S. Public Health Service.

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