Why people regain the weight after they loss it?

When mice lose weight, their brain signals that trigger hunger are altered, causing the animals to increase their food intake until they return to their original weight. Researchers have discovered a brain pathway in mice that could explain why people tend to regain lost weight. In the future, therapies targeting this pathway may help with weight maintenance after dieting.

It is still unclear what mechanism drives weight regain in nearly half of people with obesity who participate in weight loss programs and regain the lost weight within five years. However, it may be related to AgRP neurons, a type of cell in the hypothalamus that has previously been shown to play a significant role in regulating hunger. Brad Lowell of the Beth Israel Deaconess Medical Center in Massachusetts said, "When the body is low on fuel, they get activated, and when they're active, they cause strong hunger."

AgRP neurons receive signals from various brain regions through synapses. These connections can be strengthened or weakened, changing the strength of the signal that is transmitted along them. The stronger the connection, the louder the message.

To determine how weight loss affects these synapses, Lowell and his team measured brain activity in nine mice after they died, five of which had fasted for 16 hours before their brains were examined. The researchers used optogenetics to stimulate brain regions known to send signals to AgRP neurons. In response, a part of the hypothalamus in the fasted mice, called the paraventricular nucleus (PVH), was more active than in non-fasted mice. This brain region is known to be involved in metabolism and growth.

In another group of fasted mice, the researchers silenced these PVH neurons and then tracked how much food the mice ate within 24 hours. On average, these mice ate about 33% less food than the control group mice, and they regained less weight over seven days. Further experiments revealed that once the mice regained the weight they had lost due to fasting, the amplified signal from PVH neurons returned to normal.

These findings suggest that weight regain is driven by a temporary increase in signaling from PVH neurons to AgRP neurons. "Too much hunger is a medical problem, and too little hunger is a medical problem. If we're going to try to figure out how to solve these problems, we need to understand how hunger works," Lowell said.

These findings are a significant step forward. Lowell said that future therapies that reduce signaling from PVH neurons may help people maintain weight loss. However, more research is necessary to better understand the function of PVH neurons and the consequences of silencing them. "We don't yet know whether it's feasible to do this without side effects," Lowell said.

Achieving weight loss is a difficult task, but maintaining weight loss can be even more challenging. Nearly half of the people who lose weight through dieting regain the weight within five years. Research has shown that a brain pathway in mice could explain why people tend to regain lost weight. This discovery could have significant implications for weight loss maintenance strategies.

AgRP neurons, a type of cell in the hypothalamus, play a significant role in regulating hunger. When the body is low on fuel, these neurons are activated, causing strong hunger. These neurons receive signals from various brain regions through synapses. The strength of the signal transmitted along these synapses can be changed by strengthening or weakening the connections between them.

Researchers have found that weight regain is driven by a temporary increase in signaling from PVH neurons to AgRP neurons. This increased signaling causes a greater sensation of hunger, leading to increased food intake and ultimately, weight regain. By understanding this brain pathway, researchers can develop strategies to prevent weight regain and facilitate weight loss maintenance.

Future therapies that reduce signaling from PVH neurons and AgRP neurons may help people maintain weight loss. In addition, a better understanding of the function of PVH neurons and the consequences of silencing them could lead to the development of more effective weight loss treatments.

In conclusion, understanding the brain pathway that leads to weight regain is crucial for developing effective weight loss maintenance strategies. By targeting the PVH-AgRP neuron connection, researchers can develop new therapies to help people maintain weight loss and prevent weight regain. With more research, we can hope to develop even more effective treatments to help people achieve long-term weight loss success.