A “stop eating” hormone casts a wide net in the brain. After a large meal, fat cells churn out an appetite suppressant called leptin, which hits the brain’s neurons and tickles other kinds of brain cells called astrocytes. In certain situations, these astrocytes help control hunger, scientists report June 1 in Nature Neuroscience.
The results feed into a growing set of studies that elevate the status of astrocytes from mere support cells to regulators of important behavior such as eating. “That historical notion that they are cushions for the neurons to feel comfortable or protected is not the case,” says study coauthor Tamas Horvath of the Yale School of Medicine.
Scientists already knew that neurons in the brain’s hypothalamus, a region involved in feeding behavior, can sense and respond to leptin. Mice with neurons insensitive to the hormone overeat and become obese. And other studies have found evidence of leptin receptors, proteins that help a cell detect the hormone, on astrocytes. Horvath and colleagues wondered whether these leptin-sensing astrocytes influence feeding behavior.The researchers engineered mice with astrocytes in the hypothalamus that lacked the ability to detect leptin. These mice didn’t become obese. But when hungry, these mice ate more food than mice with leptin receptors on their astrocytes, Horvath and colleagues found. “To observe the animal in the normal environment, there was not a major difference,” he says. “But when you start to push them to metabolic extremes, they have different responses.” The astrocytes’ role in regulating appetite seems more subtle than the neurons’, the results suggest. Astrocytes immune to leptin also looked different. Compared with normal astrocytes, these cells had fewer tendrils that communicate with other cells, and those tendrils were shorter. The astrocytes themselves weren’t the only cells affected: Neurons that regulate feeding behavior in the hypothalamus, the same cells these astrocytes support, showed signs of listlessness, the researchers found.
Tweaking the behavior of these appetite-regulating astrocytes might be a way to treat obesity, Horvath suggests. But the brain’s leptin machinery is a problematic target, says neuroscientist Jenni Harvey of the University of Dundee in Scotland. Because fat cells produce leptin, obese people generate higher amounts of the hormone in the blood. Faced with a constant barrage of leptin, the brain’s ability to take in the hormone weakens, leading to leptin insensitivity. In these cases, adding more leptin wouldn’t do any good, she says. “Targeting the leptin system is unlikely to result in a cure for obesity.”
The newly described role for astrocytes is interesting, but “it’s just scratching the surface,” Harvey says. “There are a lot of questions that need to be answered.”