Hunger may increase after weight loss
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Researchers have identified brain pathways in mice. This may explain why people tend to regain the weight they’ve lost. Future therapies that target this pathway may help maintain weight after dieting.
Nearly half of obese people who participate in weight loss programs regain the weight they lost within five years. The mechanism that promotes this weight recovery is unknown, but may involve cells located in the hypothalamus called AgRP neurons, which have been previously shown to play a key role in regulating hunger. . Brad Lowell of Beth Israel Deaconess Medical Center in Massachusetts says, “It’s activated when the body is running low on fuel, and when activated, it causes intense hunger.
Many different brain regions send signals to AgRP neurons through connections known as synapses. These connections can be strengthened or weakened, altering the strength of the transmitted signal. The stronger the connection, the bigger the message.
To investigate how weight loss affects these synapses, Lowell and his team measured postmortem brain activity in nine mice. The researchers used optogenetics, a technique that uses light to activate cells, to stimulate brain regions known to signal AgRP neurons. Accordingly, fasted mice showed more activity in a part of the hypothalamus called the paraventricular hypothalamic nucleus (PVH) than non-fasted mice. This brain region is known to be involved in metabolism and growth.
The researchers silenced these PVH neurons in another group of fasted mice and tracked how much food the mice ate over a 24-hour period. On average, mice ate approximately 33% less food than mice in the control group and lost weight over 7 days. Further experiments revealed that amplified signaling from PVH neurons returned to normal when mice regained the weight they had lost from fasting.
Taken together, these findings suggest that weight recovery is triggered by a transient increase in signaling from PVH neurons to AgRP neurons. “Too much hunger is a medical problem, and too little hunger is a medical problem,” Lowell says. You have to understand how it works.”
These findings are an important step in that direction. For example, future treatments that attenuate the signaling from PVH neurons could help people maintain weight loss, he says. Further research is needed to better understand the “Can it be done without side effects? We don’t know yet,” he says Lowell.
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