Nature sub-journal: Cheng Wenwen et al. draw a map of the posterior brain neurons that control diet to help develop better weight loss drugs

Written byJia Yu Geng

Edited by wang multi-fish

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Obesity is due to the fact that long-term calorie intake exceeds energy expenditure promotes excessive energy storage in the body (mainly triglycerides), which in turn leads to obesity

Usually, delicious food is always addictive, and the memory after tasting, no matter how many years have passed, can still be instantly recognized when tasted again, and while lamenting "it is a familiar taste", it will also overeat

The above rules make it not difficult for us to find: delicious food is easy to make people fat; Foods that are difficult to eat can suppress appetite and help to lose weight

The prevailing view is also that weight gain is mainly attributable to poor

Previously, scientists had a good understanding of the physiological processes that regulate blood pressure, and as a result, many effective antihypertensive drugs

On July 25, 2022, the Laboratory of Martin G.

This review reviews recent insights into the understanding of the hindbrain neurons that control eating, and builds a model of relevant hindbrain circuits to predict which neurons can suppress appetite

Previously, scientists have found that many organ systems are involved in controlling energy homeostasis, but the brain plays the most critical role
in it.

There are a large number of neural circuits in the brain that constantly evaluate and integrate metabolic, gastrointestinal, endocrine, and neuronal signals, and inform a system that matches energy intake and consumption to maintain long-term energy homeostasis
.

In addition, genome-wide association studies (GWAS) revealed that genes that affect body mass index (BMI) are expressed in the brain and suggested that significant differences in BMI in populations are primarily caused
by altered brain function.

In the central nervous system, the leptin system and the melanin cortical system have been found to play an important
role in controlling energy homeostasis.

Moreover, because the leptin regulatory circuit is located in the hypothalamus, many studies related to energy homeostasis have also focused on the hypothalamus
.

However, recent studies have found that these biological factors do not directly control eating behavior
.

Instead, the hypothalamic circuits that regulate food intake and energy homeostasis target key components of
the dorsal vagus complex in the posterior brain.

The dorsal vagus nerve complex (DVC, see figure below) is an area located in the brainstem that integrates sensory information from the gastrointestinal tract with rhythmic patterns that coordinate food intake, including feelings of fullness (or nausea)
after eating.

There are several nuclei in DVCs that are critical to controlling food intake, including the posterior region (AP), the solitary nucleus (NTS), and the dorsal motor nucleus (DMV) of the vagus nerve, as well as major entry points
into the brain that reflect intestinal state information.

The paper's corresponding author, Martin G.
Myers Jr.
, said that everything the hypothalamus does eventually converges on the brainstem
.

The brainstem is very important in controlling eating because it takes all sorts of information from your gut, including stomach dilation, whether nutrients are being ingested, and integrates that information with the hypothalamus's information about nutritional needs, which is then passed on to autonomous rhythmic patterns
that control food intake.

The posterior region receives some input signals from the vagus nerve, but the structure is located outside the blood-brain barrier and therefore has a unique ability to sense signals of blood propagation, including various ingestion-related humoral signals
from the gut.

A previous mouse study in myers lab established a single-cell profile of the dorsal motor nucleus of the vagus nerve and revealed two different types of solitary nucleus (AP) neurons that regulate food intake: one causes nausea and disgust; And the other won't
.

This review combines these findings with other recently published literature, on the basis of which a new brainstem neural circuit map is established that can predict which groups of neurons control food intake or cause gastrointestinal reactions such as nausea or disgust; And discussed how this information can be used to identify more effective treatments for
obesity.

Many of the neurons they point out are new and effective targets for weight loss drugs, for example, a class of diabetes drugs called GLP1 receptor agonists can lower blood sugar and help reduce dietary intake
.

Given the widespread crosstalk between solitary nucleus neurons, the researchers speculate that solitary nucleus-related neurons may also mediate the appetite-suppressing effects of
GLP-1.

Myers says there's a bunch of GLP1 neurons in the brainstem that, if you turn them on, they can stop eating, but at the same time cause serious side effects
.

But maybe there's another set of neurons that can make you stop eating, and it won't make you feel bad
.

Having a detailed map of these neurons and understanding the role of these potential targets could help develop weight loss drugs with fewer side effects
.

In conclusion, this review reviews recent advances in the hindbrain neurons that control eating, particularly those located in the posterior polar region and solitary nucleus
.

The researchers linked this information to a map of neural circuits in the brainstem and built models of posterior brain circuits that control food intake and energy homeostasis, providing important clues
for further research and development of drugs that treat obesity with fewer side effects.

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