Genetic risk of developing obesity is driven by variants that affect the
brain

Date:
September 29, 2020
Source:
University of Copenhagen The Faculty of Health and Medical Sciences
Summary:
Some people are at higher risk of developing obesity because they
possess genetic variants that affect how the brain processes sensory
information and regulates feeding and behavior. The findings support
a growing body of evidence that obesity is a disease whose roots
are in the brain.



FULL STORY ==========================================================================
Over the past decade, scientists have identified hundreds of different
genetic variants that increase a person's risk of developing obesity. But
a lot of work remains to understand how these variants translate into
obesity. Now scientists at the University of Copenhagen have identified populations of cells in the body that play a role in the development of
the disease -- and they are all in the brain.


==========================================================================
"Our results provide evidence that biological processes outside the
traditional organs investigated in obesity research, such as fat cells,
play a key role in human obesity," says Associate Professor Tune H Pers
from the Novo Nordisk Foundation Center for Basic Metabolic Research
(CBMR), at the University of Copenhagen, who published his team's findings
in the internationally-recognized journal eLife.

"We identified cell types in the brain that regulate memory, behavior and processing of sensory information that are involved in the development of
the disease. Further investigation of these areas of the brain may tell
us why some of us are more susceptible to develop obesity than others."
A mosaic of brain cell populations contribute to obesity The discovery
was made by developing computational tools that combine two different
sets of data. The first set is genome-wide association study data from
around 450,000 people. This data compares a person's health and physical attributes, such as their body weight, to their unique genome. Doing so
reveals that people with obesity are much more likely to have a range
of genetic variants in common.

The second set is single-cell RNA-sequencing data of more than 700
different types of mouse cell populations. Different cells express
different parts of the genome, so this data set contains the unique
genetic fingerprint for each cell population.

The team at CBMR integrated the two data sets and found that the genetic variants, which are strongly associated with obesity, are near genes
expressed by 26 cell populations acting as different types of neurons.

Obesity is not a lack of willpower We already know that the brain plays
an important role in obesity by regulating how the body maintains its
energy needs. It does so by processing signals from within the body
about the energy stores and food intake, as well as external signals
such as the sight and smell of food.

The new findings suggest that a person's risk of developing obesity is
driven by populations of cells that process sensory stimuli and direct
actions related to feeding and behavior. They also identified specific
brain cell types that support a role of learning and memory in obesity.

"The next step is to explore how defects in parts of the brain
traditionally known to regulate memory and integration of sensory signals actually makes us more vulnerable to become obese," says Tune H Pers.

"Our journey, to understand why some of us develop obesity, has only
just begun. Our findings reinforce the growing body of evidence that
obesity is far more complex than previously recognized and not can be
reduced to a simple question about lack of willpower."

========================================================================== Story Source: Materials provided
by University_of_Copenhagen_The_Faculty_of_Health_and
Medical_Sciences. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Pascal N Timshel, Jonatan J Thompson, Tune H Pers. Genetic
mapping of
etiologic brain cell types for obesity. eLife, 2020; 9 DOI:
10.7554/ eLife.55851 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/09/200929123437.htm

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