How the liver can control the brain and behavior – Neuroscience News

Summary: The liver appears to play an important role in regulating feeding behaviors in mice.

source: Yale

A new study at Yale University has found that the liver plays a key role in regulating feeding behavior in mice, a finding that may have implications for people with eating disorders and metabolic diseases.

The study, conducted in collaboration with colleagues in Germany, also adds to a growing body of evidence showing that the most advanced part of the brain, the cerebral cortex, is affected by the rest of the body, and not just the other way around. .

Tamas Horvath, the Jan and David Wallace Professor of Comparative Medicine at Yale University School of Medicine and one of the senior authors of the study published June 27 in nature metabolism.

In a series of experiments, the research team uncovered a circuit through which the brain and liver communicate with each other — and control them. The main participants in this conversation are a group of cells known as neurons associated with protein (AgRP) neurons, which are located in the hypothalamus of the brain, and a type of fat secreted by the liver called lysophosphatidylcholine (LPC).

AgRP neurons, which communicate with the cerebral cortex, the outer layer of the brain associated with complex behaviors and abilities, are necessary to enhance the feeling of hunger. But they also communicate with other parts of the body, such as the liver and pancreas; When a person is hungry, these neurons play an important role in releasing fats from the body’s fat stores.

Once the liver secretes LPC, an enzyme in the blood quickly converts it into lysophosphatidic acid, or LPA. Other researchers have shown that LPA can alter the activity of neurons in the brain.

In this study, the researchers noted that after fasting, the mice had higher levels of LPA in both their blood and cerebrospinal fluid, the special fluid found within the central nervous system. This rise in LPA levels caused increased activity of neurons in the cortex, resulting in increased appetite after fasting. All of these effects were dependent on the function of the AgRP neuron.

These findings suggest a circuit in which AgRP neurons regulate liver and lipid secretion and in which those lipids circulate back to the brain where they affect the cortex and its function.

Horvath says more research is needed to determine whether a similar circuit exists in humans, but he and his colleagues have found some evidence that this may occur.

In a series of experiments, the research team uncovered a circuit through which the brain and liver communicate with each other — and control them. The image is in the public domain

Mice with a mutation that results in increased neuronal activity caused by LPA eat more and weigh more than their counterparts in model mice. People with this genetic mutation tend to have higher body mass indexes and a greater prevalence of type 2 diabetes than people without this mutation.

“We still need to explore more rigorously whether these mechanisms are relevant to humans, but if they are, we can begin to investigate whether we can exploit the mechanisms in order to treat eating disorders and other conditions,” Horvath said.

But this shows that the liver can be a major driver of behavior. It adds to the argument that staying in the brain to understand the brain is not enough.”

Other Yale authors on the study are Bernardo Stutz, Zhong Wu Liu, and Mateja Sestan-Besa.

About this neuroscience and behavioral research news

author: Mallory Locklear
source: Yale
Contact: Mallory Locklear – Yale
picture: The image is in the public domain

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AgRP neurons control feeding behavior at cortical synapses via peripheral derived lysophospholipidsWritten by Heiko Endel et al. nature metabolism


Summary

AgRP neurons control feeding behavior at cortical synapses via peripheral derived lysophospholipids

Phospholipid levels are affected by peripheral metabolism. Within the central nervous system, synaptic phospholipids regulate glutamate transmission and cortical excitability. Whether changes in peripheral metabolism affect brain lipid levels and cortical excitability remains unknown.

Here, we show that levels of lysophosphatidic acid (LPA) species in blood and cerebrospinal fluid rise after overnight fasting and lead to increased cortical excitability. Cortical excitation associated with LPA increases fasting-induced hypereating, and decreases after inhibition of LPA synthesis.

Mice that express a human mutation (Prg-1 . programR346T) leading to increased display of cortical excitability mediated by synaptic fat, increased fasting-induced hyperphagia. Accordingly, people with this mutation have a higher body mass index and a higher prevalence of type 2 diabetes.

We further demonstrate that the effects of LPA after fasting are under the control of hypothalamic-associated peptide neurons (AgRP). Fasting-induced depletion of AgRP-expressing cells in adult mice reduces circulating LPAs, as well as cortical excitability, while limiting overeating.

These results reveal a direct effect of LPAs circulating under the control of AgRP neurons on cortical excitability, revealing an alternative non-neuronal pathway through which the hypothalamus can exert a strong influence on the cortex and thus influence food intake.

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