New treatment to combat obesity and heart disease

Date:
March 4, 2022
Source:
University of Texas at San Antonio
Summary:
An interdisciplinary research team has successfully developed
an innovative inhibitor that shows promise in fighting obesity
and potentially preventing heart disease. The team developed an
anti-obesity drug that blocks the effects of cytochrome P450 8B1,
the enzyme linked to cholesterol absorption and obesity.



FULL STORY ==========================================================================
An interdisciplinary research team at The University of Texas at
San Antonio has successfully developed an innovative inhibitor that
shows promise in fighting obesity and potentially preventing heart
disease. Francis Yoshimoto, an assistant professor in the UTSA College
of Sciences' Department of Chemistry, is leading a team that developed
an anti-obesity drug that blocks the effects of cytochrome P450 8B1,
the enzyme linked to cholesterol absorption and obesity.


========================================================================== Yoshimoto collaborated with Eunhee Chung, an associate professor in the
UTSA College of Health, Community and Policy's Department of Kinesiology
to test the new drug. After designing and synthesizing it, Yoshimoto sent
test samples to Chung's National Institutes of Health-funded laboratory,
where she and her research team are conducting research on the effects
of bioactive compounds - - chemicals found in small amounts in plants
and certain foods -- and how exercise can be used to treat obesity and associated metabolic disorders.

Their research findings were published in the February 2022 issue of
the scientific journal, Steroids.

"Growing up, I dreamed of helping my family members, who were affected
by obesity and heart disease and other medical conditions," Yoshimoto
said. "This dream is now turning into a reality, as we have developed
a small molecule that can be used to fight obesity, a problem seen in
many families around the world." "As an exercise physiologist, I truly
believe exercise is the best medicine to fight against noncommunicable diseases," added Chung. "Unfortunately, the adherence to exercise is
quite low, and the prevalence of obesity is continuously rising. Based
on promising data, I have high hopes of further testing Dr. Yoshimoto's inhibitor." UTSA's drug has the potential to stop the activity of P450
8B1, the enzyme that creates cholic acid in the body. This inhibition,
in turn, decreases cholesterol absorption. This process may hold the key
to treating obesity- associated metabolic disorders and other diseases
linked to obesity, such as heart disease and diabetes.

The team's research included treating mice with the inhibitor drug for
seven days. The result was a decrease in the levels of glucose in their
blood - - despite having been fed a high-fat and high-sucrose diet --
without affects to their body weight. The results demonstrate how a
P450 8B1 inhibitor could lead to a healthier metabolic profile and
its potential could lead to developing a therapeutic strategy to treat obesity-associated insulin resistance.

Yoshimoto and Chung's work is representative of UTSA's mission to
develop solutions for complex challenges that will improve the health and well-being of society. Creating a drug effective in preventing obesity
could improve quality of life around the world.

According to the World Health Organization, 1.9 billion adults worldwide
were overweight in 2016, and 650 million were classified as obese. Closer
to home, one in every four deaths in the U.S. is due to heart disease,
of which obesity is a major contributor. Locally, 71% of adults are
overweight or obese, according to a recent report from the San Antonio Metropolitan Health District.

"These results show how our research in synthetic chemistry can
significantly contribute to the well-being of society by treating obesity
and heart disease," Yoshimoto said.

Yoshimoto's medicinal chemistry research was made possible by the Max
and Minnie Tomerlin Voelcker Fund, which contributed $450k in 2019 to
support anti- obesity research.

Chung's research was supported by the National Institutes of Health
[NIH, NIGMS, grant GM125603].

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


========================================================================== Journal Reference:
1. Eunhee Chung, Samuel D. Offei, U-Ter Aondo Jia, Juan Estevez,
Yessenia
Perez, Hadi D. Arman, Francis K. Yoshimoto. A synthesis of
a rationally designed inhibitor of cytochrome P450 8B1, a
therapeutic target to treat obesity. Steroids, 2022; 178: 108952
DOI: 10.1016/j.steroids.2021.108952 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/03/220304090352.htm

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