Summary: The liver appears to play an important role in regulating eating behaviors in mice.
A new study from Yale has found that the liver plays a major role in regulating eating behavior in mice, a finding that could have implications for people with eating disorders and metabolic diseases.
The study, which was carried out in collaboration with colleagues in Germany, also adds to a growing body of evidence that shows 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. .
“One of the takeaways from this work is that the conventional way of trying to understand brain function by just looking at the brain itself doesn’t give you the full picture,” said Tamas Horvath, professor of medicine. compared Jean and David W. Wallace at Yale. School of Medicine and lead author of the study published June 27 in Natural metabolism.
In a series of experiments, the research team discovered a circuit through which the brain and liver communicate and control each other. The two key participants in this conversation are a group of cells known as agouti-related protein (AgRP) neurons, which are found in the hypothalamus region of the brain, and a type of lipid 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 essential for promoting feelings of hunger. But they also communicate with other parts of the body, such as the liver and pancreas; when humans are hungry, these neurons play a critical role in releasing lipids from body fat stores.
Once LPC is secreted by the liver, an enzyme in the blood quickly converts it to lysophosphatidic acid or LPA. Other researchers have shown that LPA can alter neuronal activity in the brain.
In this study, the researchers observed that after fasting, the mice had higher levels of LPA in the blood and in the cerebrospinal fluid, the special fluid found in the central nervous system. This increase in LPA levels caused an increase in neural activity in the cortex, which triggered increased appetite after fasting. And all of these effects depended on the function of AgRP neurons.
These results suggest a circuit in which AgRP neurons regulate the release of liver and lipids and in which these lipids return to the brain where they affect the cortex and its functions.
Horvath says more research is needed to determine if a similar circuit exists in humans, but he and his colleagues have found evidence that it might.
Mice that undergo a mutation leading to greater LPA-induced neuronal activity eat more and weigh more than their typical mouse counterparts. Humans with this same genetic mutation tend to have higher body mass indices and a greater prevalence of type 2 diabetes than people without the mutation.
“We still need to explore more rigorously whether these mechanisms are relevant to humans, but if they are, then we can begin to investigate whether we can harness the mechanisms to treat eating disorders and other conditions.” , said Horvath.
“But it shows that the liver can be a major driver of behavior. And that adds to the argument that staying in the brain to understand the brain is not enough.
The other authors of the Yale study are Bernardo Stutz, Zhong-Wu Liu and Matija Sestan-Pesa.
About this neuroscience and behavior research news
Author: Mallory Locklear
Contact: Mallory Locklear–Yale
Image: Image is in public domain
Original research: Access closed.
“AgRP neurons control feeding behavior at cortical synapses via peripherally derived lysophospholipids” by Heiko Endle et al. Natural metabolism
AgRP neurons control feeding behavior at cortical synapses via peripherally derived lysophospholipids
Phospholipid levels are influenced by peripheral metabolism. Within the central nervous system, synaptic phospholipids regulate glutamatergic transmission and cortical excitability. It is unknown whether changes in peripheral metabolism affect brain lipid levels and cortical excitability.
Here, we show that lysophosphatidic acid (LPA) species levels in blood and cerebrospinal fluid are elevated after overnight fasting and lead to higher cortical excitability. LPA-related cortical excitability increases in fasting-induced hyperphagia and decreases after inhibition of LPA synthesis.
Mouse expressing a human mutation (Prg-1R346T) leading to increased synaptic lipid-mediated cortical excitability display increased fasting-induced hyperphagia. As a result, human subjects carrying this mutation have a higher body mass index and prevalence of type 2 diabetes.
We further show that the effects of LPA after fasting are under the control of hypothalamic agouti-related peptide (AgRP) neurons. Depletion of AgRP-expressing cells in adult mice decreases fasting-induced elevation of circulating LPAs, as well as cortical excitability, while attenuating hyperphagia.
These results reveal a direct influence of circulating LPAs under the control of hypothalamic AgRP neurons on cortical excitability, unveiling an alternative non-neuronal pathway by which the hypothalamus can exert a robust impact on the cortex and thus affect food intake.
#Liver #Control #Brain #Behavior #Neuroscience #News