Sci. Aging Knowl. Environ., 14 April 2004
Fat-produced hormone infiltrates the brain to slash weight
That slice of chocolate cake is going straight to the hips, many a dieter frets after a splurge. Whether that's true depends in part on the fat our calorie counter already packs, according to new work. The study shows that a hormone released by fat tissue heads for the brain and helps tweak energy balance and body mass. Understanding how the hormone throws its weight around might help researchers develop therapies to keep our waistlines in check.
Fat is more than padding. It dispatches messages that help adjust weight and metabolism. For example, fat exudes the hormone leptin, which sounds like a dieter's dream. Leptin reins in appetite and boosts energy use. Mice and people with faulty leptin genes overeat and blimp out. Fat releases another hormone called adiponectin, which spurs the liver to cut blood-glucose quantities and burn lipids. Researchers have suspected that adiponectin also trims body weight. To produce its effects, leptin rouses the liver and muscles, but it also stimulates brain cells that influence appetite and energy use. To understand how adiponectin alters metabolism, endocrinologist Rexford Ahima of the University of Pennsylvania in Philadelphia and colleagues wanted to find out whether it too enters the brain.
The fluid that bathes the brain and spinal cord carries small amounts of adiponectin, the researchers discovered. Injecting tiny doses of the hormone into mouse brains hiked metabolic rate, increased fat burning, and cut body weight. But unlike leptin, adiponectin didn't diminish the rodents' appetite. To find cells activated by adiponectin, the researchers tested for a molecule produced by stimulated neurons. Cells making the molecule clustered in the paraventricular nucleus, a brain region that helps coordinate food intake and heat production. Leptin activates the same region, but it prods other areas as well.
To determine whether the hormones collaborate, the researchers tested their effects on tubby mice that lack leptin. Animals receiving either adiponectin or leptin lost fat and shed grams, but together, the hormones shrank the animals faster. That finding suggests that although neither hormone requires the other, the two team up to speed weight loss, says Ahima. The results indicate that adiponectin spurs the brain to crank up energy consumption but not to reduce eating. Adiponectin might not make a good drug, Ahima says; leptin never matched the high expectations its discovery provoked. But further research on the molecule might help researchers design compounds to help us burn off extra pounds, cut blood glucose, and trim fat, he says.
The study "firmly establishes that adiponectin has central nervous system actions that relate to energy balance," says endocrinologist Jeffrey Flier of Beth Israel Deaconess Medical Center in Boston. Endocrinologist Michael Spurlock of Purdue University in West Lafayette, Indiana, points out that establishing adiponectin's influence on the brain is crucial for discovering how it works. Now, he says, researchers need to figure out how it enters that organ and tease apart the signaling pathways that transmit its directives. Such studies might reveal a way to prevent that slice of chocolate cake from settling in just below the waistline.
April 14, 2004
Science of Aging Knowledge Environment. ISSN 1539-6150