Scientists
have implicated specific neurons in the lateral hypothalamic area, a region
involved in survival mechanisms such as food intake, in signaling to the brain
when to stop eating. This mechanism is impaired in obese mice.
How does obesity trick the brain into
sending a signal that says to keep on eating?
Obesity is a worldwide problem,
with the World Health Organization (WHO) estimating that 650 million people across the globe were obese
in 2016.
Many experts point the finger at overeating and a sedentary
lifestyle as the root causes of the obesity epidemic.
However, any action that we take has
consequences at the molecular level, and experts know little detail about how
our brains behave as the readings on the scales slowly go up.
Scientists from the Department of Psychiatry at the University
of North Carolina in Chapel Hill, along with collaborators in the United
States, Sweden, and the United Kingdom, sought to unravel the molecular
pathways at play in the brains of mice with obesity.
Garrett Stuber, a professor of neurobiology who has now moved to
the Center for the Neurobiology of Addiction, Pain, and Emotion at the
University of Washington in Seattle, is the senior author of the team's
results, which feature in the journal Science.
Identifying the 'brake on feeding'
Stuber and his collaborators study a specific area of the brain
called the lateral hypothalamic area (LHA).
"The LHA has long been known to play [a] role in promoting
feeding behavior, but the exact cell types that contribute to feeding within
this brain structure are not well-defined," explained Stuber about his
research to Medical
News Today.
Analyzing gene expression in individual cells in the LHA in
obese mice and comparing it to that in normal mice, the team found prominent
changes in vesicular glutamate transporter type-2 (Vglut2)–expressing neurons.
These cells use glutamate as their fast-acting neurotransmitter.
However, changes in gene expression do not necessarily equate to
changes in function.
Stuber dug deeper and used a combination of techniques to
visualize individual LHAVglut2 neurons when the team gave mice sucrose, a common sugar
comprising glucose and fructose.
The researchers found that sucrose consumption resulted in the
cells' activation. However, the response was nuanced. Mice that were not very
hungry showed strong activation of their LHAVglut2neurons, whereas those
that had fasted for 24 hours had an attenuated response.
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Stuber and his colleagues, therefore,
suggest that LHAVglut2 neurons play a role in the
suppression of feeding by telling our brain when to stop eating. They call this
the "brake on feeding."
"We hypothesize that the excitatory LHAVglut2 signal represents
the activation of a brake on feeding to suppress further food intake,"
they write.
Next, the team investigated how obesity affects the activity of
these cells in mice that ate a high fat diet for 12 weeks to induce obesity.
"Whereas LHAVglut2 neurons from control mice maintained their responsivity to
sucrose consumption, LHAVglut2 neurons from [the high fat diet] mice became progressively
less responsive to sucrose consumption and less active at rest," the team
writes in the study paper.
In other words, the neurons did not send such a strong
"stop eating" signal to the brain when the mice consumed sugar or
when the mice were resting. Instead, the animals overate and developed obesity.
Obesity 'impairs break on food intake'
When MNT asked whether he was surprised to see such a stunted
response by the cells, Stuber explained, "Yes, the imaging results, which
show that LHA glutamate cells are downregulated by high fat diet exposure (our
experimental model of obesity) was surprising to us."
"When these neurons are activated, mice halt sucrose
licking and avoid locations paired with LHAVglut2 stimulation. Thus,
activation of LHAVglut2 neurons may serve as a brake on feeding," comments
Stephanie Borgland, a professor at the Hotchkiss Brain Institute at the
University of Calgary in Canada, in an accompanying Perspective article
in Science.
"Given that
activation of these neurons also leads to escape and avoidance behaviors, these
neurons may be involved in the switch from foraging to escaping to promote
survival, which is consistent with other homeostatic functions of the
hypothalamus."
Source: Medical News Today
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