Leptin and obesity

For nearly a decade, scientists have known that leptin plays an important fat-burning role in humans. But the map of leptin’s path through the body – the key to understanding how and why the hormone works – is still incomplete.

Now a small but critical section of that map is charted, based on new research conducted at Brown Medical School and Rhode Island Hospital and at Harvard Medical School and Beth Israel Deaconess Medical Center.

The research team found that leptin triggers production of the active form of a peptide – áMSH – in the hypothalamus, the small area in the base of the brain that controls hunger and metabolism. Researchers say this peptide, or small protein, is one of the body’s most powerful metabolism booster signals, sending a fast, strong message to the brain to burn calories.

This message is then sent to another part of the hypothalamus, where another peptide is produced and released. This stimulates the pituitary gland, which secretes a hormone that relays the message to the thyroid, the master of metabolism. Once activated, the thyroid gland then spreads word to the body’s cells to increase energy production.

Research results are published in the online early edition of the Proceedings of the National Academy of Sciences for the week of July 26. The team’s contribution to the understanding of leptin function – how áMSH is produced and its power as a metabolic messenger – could help in the search for an obesity treatment, said Eduardo Nillni, an associate professor in the Department of Medicine at Brown Medical School and in Brown’s Department of Molecular Biology, Cell Biology and Biochemistry. Nillni is also a senior investigator in the Division of Endocrinology at Rhode Island Hospital.

“If somehow, through a drug, you can increase activity of áMSH, you’d force the body to burn more calories and lose weight,” Nillni said. “That would help so many people.”

According to the federal Centers for Disease Control and Prevention, 61 percent of adults are overweight or obese and 13 percent of children and adolescents are seriously overweight. This epidemic exacts a steep toll: Each year, about 300,000 Americans die of obesity-related causes. The economic cost of obesity was about $117 billion in 2000, the CDC also reports.

Working with grants from the National Institutes of Health, researchers studied chemical changes in the brains of mice and rats injected with leptin to arrive at their findings.

The Brown/Rhode Island Hospital research team included Nillni and Ronald Stuart. Christian Bjorbaek, Li Guo and Heike Munzberg worked on the project through Harvard and the Beth Israel Deaconess Medical Center.