Decoding the Surprisingly Active Life Of Fat Cells

The pivotal discovery came in 1994, when scientists identified a hormone produced by fat cells that they dubbed leptin. Among other things, leptin tells the brain how much fat is in the body. That raised the hope that it could be used as an anti-obesity drug, but that has yet to pan out. Still, the discovery revealed for the first time a direct communication link between the brain and fat cells.

That insight spawned a new wave of research that led to the identification of other fat signals and the new paradigm for the role of fat in the body. Scientists now call fat an "endocrine organ," akin to the thyroid and adrenal glands that orchestrate many body functions.

"But it's probably the biggest endocrine organ in the body," said Jeffrey M. Friedman of the Rockefeller University in New York, who led the team that discovered leptin. "Fat tissue plays such a vital role for the survival of any species that it should really come as no surprise that it would be involved in such dynamic regulation."

Scientists have long known, for example, that fat cells play a role in synthesizing sex hormones such as estrogen, which enables the cells to regulate the reproductive process. That explains, for example, why ballerinas, female professional athletes and other women who are very thin often stop menstruating.

"If a female doesn't have enough energy stored, the pregnancy can be in jeopardy and so reproduction is shut down. The body is waiting for more favorable conditions," Friedman said.

But far beyond simply monitoring energy reserves, fat cells are the hub of a complex communication system that regulates many metabolic functions, continuously telling the brain how much energy the body has left, signaling muscles when they can burn fat, instructing the liver and other organs when to replenish fat stores, and controlling the flow of energy in and out of cells.

One of the most important newly recognized players in that finely tuned system is a protein called adiponectin, which affects the liver and muscles.

"This hormone lowers blood glucose by blocking its production in the liver and by increasing the burning by muscle to make energy," said Harvey Lodish, a professor of biology at the Massachusetts Institute of Technology. "It activates part of the same signaling pathway in muscles [that is] activated by exercise."

Adiponectin levels fall as fat levels rise. Because the hormone affects how sensitive cells are to insulin, scientists believe it helps explain how obesity increases the risk for diabetes.

"It's been pretty well established now that levels of this protein are a good measurement of insulin sensitivity," said Philipp Scherer, a cell biologist at the Albert Einstein College of Medicine in New York who identified the substance.

Drugs that affect adiponectin, therefore, may help prevent or treat diabetes. The drugmaker Serono Inc., has started studying adiponectin, both as a possible preventative for diabetes and as a weight-loss drug.

Soon after adiponectin's importance was recognized, scientists discovered another fat cell hormone called resistin, which also appears to play a crucial role in insulin sensitivity and energy storage.

"It's clearly important, but its exact mechanisms are still something we're trying to understand," said Mitchell A. Lazar, an endocrinologist at the University of Pennsylvania School of Medicine who discovered the hormone. "So far we haven't found net changes in energy storage -- weight is not affected in a significant way by either too much or too little resistin."

At the same time, scientists have come to the surprising conclusion that fat has the power to mimic the effects of the body's immune system, in particular by provoking an inflammatory response.