Resistance To Leptin Contributes ...( Insensitivity to the protein leptin w...)

Insensitivity to the protein leptin, which helps the body regulate its fat stores, contributes to obesity in mice according to the first formal study of leptin intolerance, report scientists in the Aug. 5 Proceedings of the National Academy of Sciences. The findings also provide clues about leptin's action in the nervous system and may help to explain some forms of obesity that affect humans, including more than 50 million overweight adult Americans, the researchers note.

"We knew obese mice and humans generally have high levels of leptin in their blood, which suggested that the protein was not fully active. Our new research directly shows that resistance to leptin can cause obesity," explains senior author Jeffrey Friedman, M.D., Ph.D., professor at The Rockefeller University and an investigator with Howard Hughes Medical Institute (HHMI).

Some investigators have suggested that leptin's principal role is to suppress the body's response to starvation. The new study also suggests that receiving extra leptin adjusts a mouse's 'set point' for the body weight to a lower-- but stable level --by reducing food intake without an accompanying decrease in energy use.

"These data confirm that leptin plays an important role in the body's response to weight gain. This result suggests that lean animals increase their production of leptin to return their weight to the set point," explains first author Jeffrey L. Halaas, B.S., biomedical fellow at Rockefeller. "Also, leptin acts to blunt the reduction in energy use that typically follows a reduction in the number of calories eaten."

In previous studies, Friedman and his colleagues discovered leptin and documented weight loss in genetically obese and normal mice given daily injections of the protein for two weeks. These early studies required high dose injections of leptin. In the current study, much lower doses were effective in reducing weight when the hormone was delivered as
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Contact: Marion E. Glick
runews@rockvax.rockefeller.edu
212-327-7900
Rockefeller University
1-Aug-1997