UVA Reveals How Genetic Differences In Fat Shape Men And Women’s Health Risks

New University of Virginia research is revealing how
genetic differences in the fat in men’s and women’s bodies
affect the diseases each sex is likely to
get.

Researchers Mete Civelek, PhD, Warren Anderson,
PhD, and their collaborators have determined that
differences in fat storage and formation in men and women
strongly affect the activity of 162 different genes found in
fat tissue. Further, 13 of the genes come in variants that
have different effects in men and women.

Some of those
genes identified have already been connected with conditions
such as type 2 diabetes and cardiovascular disease. The
findings help explain the differing health risks men and
women face, and they set the stage for better, more targeted
treatments.

“Obesity is associated with a number of
health risks, and how men and women store excess calories as
fat makes a difference in how they have different
susceptibilities to common diseases,” said Civelek, of
UVA’s Department of Biomedical Engineering, a joint
program of UVA’s School of Medicine and School of
Engineering. 

“We studied people of different
ethnicities and health conditions, and we found a group of
genes that are different in their abundance between men and
women independent of ethnicity or health
status.”

Fat Genes

One of the great
challenges of genetic research is the tremendous volume of
information it produces. Previous studies had identified
thousands of genes found in fat that appeared to behave
differently based on sex, but Civelek and his collaborators
found “robust” differences in only 162. This was based
on the researchers’ analysis of approximately 3,000 human
samples collected from geographically and ethnically diverse
populations.

“By combining a variety of data
resources, we were able to identify specific genes that
could be targeted to elicit distinct therapeutic outcomes in
men and women.” said Anderson, a member of Civelek’s
lab.

Digging deeper, the researchers identified six
specific genes that were particularly influential in terms
of regulating the activity of fat tissue. “We can now
focus on these six genes as potential therapeutic
targets,” Civelek said.

The findings are
particularly notable because there has been much research
into sex differences in fat tissue in terms of its
distribution (pear shaped vs. apple shaped bodies, for
example) and other aspects, but the important genetic
contributions have remained relatively
unexplored.

“We believe our findings
will be beneficial in precision medicine efforts to find
drug targets that can help with specific problems that men
and women face,” Civelek said. “For example, men are
more prone to cardiovascular disorders and women to obesity.
The fat genes we identified could contribute to the severity
of those illnesses and how men and women respond to
treatment differently.”

Findings
Published

The researchers have published their
findings in the scientific journal Genome Research. The
research team consisted of Anderson, Joon Yuhl Soh, Sarah E.
Innis, Alexis Dimanche, Lijiang Ma, Carl D. Langefeld, Mary
E. Comeau, Swapan K. Das, Eric E. Schadt, Johan L.M.
Bjorkegren and
Civelek.

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