Insulin's Alter Ego

What makes a fat cell fat? Overeating, of course, is one reason these cells pack away fat molecules. Now scientists have found that a protein called leptin, known to suppress appetite, also lights a fire under individual cells--not just fat cells, but ones in muscle and the pancreas too--to burn up fat stores. The finding, reported in today's issue of the Proceedings of the National Academy of Sciences, suggests that leptin could be the hormone insulin's alter ego: While insulin socks fat away in individual cells, leptin may be the key to releasing it.

Previous studies have shown that leptin triggers a brain region called the hypothalamus to send out unidentified signals that suppress appetite. To probe the way leptin influences individual cells, Roger Unger and his colleagues at the University of Texas Southwestern Medical Center in Dallas injected mice with a retrovirus carrying extra copies of the leptin gene, which the virus inserted into the mouse genome. Mice with elevated blood leptin levels stored 80% less fat in muscle, liver, and pancreatic cells than did untreated littermates on an identical diet.

Unger's team next cultured pancreatic cells with leptin and palmitate (a long-chain fat molecule), labeled with tritium, a radioactive form of hydrogen. They found that pancreatic cells bathed in leptin took up 52% less of the labeled palmitate and burned 42% more of their fat stores than did cells in a leptin-free culture.

The findings suggest that in addition to suppressing appetite through the brain, leptin acts as a cellular micromanager, regulating energy storage in individual cells along with insulin. Thus, says Unger, leptin doesn't exist simply "to turn people into fashion models." The work "raises strong indications" that leptin acts on individual cells, says Jeffrey Flier, an endocrinologist at Beth Israel Deaconess Medical Center in Boston. But he cautions that "it's not clear at this point" whether the hypothalamus or individual cells are leptin's primary target.