‘Moonlighting’ Metabolism Molecule May Play Role in Eating Disorders

March 5, 2019 by   |   Leave a Comment

Third-year neuroscience major Dove-Anna Johnson is researching the role of a molecule, p75, in eating disorders. (Photo by Dan Addison, University Communications)

Dove-Anna Johnson spent last summer trying to determine what creates eating disorders.

Johnson, a University of Virginia student whose research is funded through a Harrison Undergraduate Research Grant, investigated the function of a molecule, p75, that has been known to be important in forming the nervous system, but which also “moonlights” in other jobs in the body, such as controlling metabolism and body weight.

Working in the laboratory of Christopher Deppmann, an associate professor of biology, Johnson, a third-year neuroscience major, started in one direction, thinking that p75 was acting upon nerve tissues and fat to reduce weight.

“Instead, upon conducting a new experiment where we food-restricted mice to eat for only three hours a day, p75 seemed to be important to regulate feeding behavior,” she said.

“We’ve actually discovered that p75 seems to act in the brain to control how much we eat, especially when we’re hungry,” Deppmann, director of the Neuroscience Graduate Program, said. “In fact, when we get rid of p75 in parts of the brains of mice, the mice don’t eat as much food when they’re hungry compared to mice that have p75.”

Deppmann said the work could open new opportunities to better understand the signals that cause people to feel hungry and be motivated to eat and the parts of the brain that control eating behavior, and could lead to treatment options for eating disorders, including obesity and anorexia nervosa.

Johnson further examined the specific location and function of p75 in metabolic regulation by conducting dietary fasting experiments, analyzing changes in protein concentrations and measuring expression of neuronal markers. From these experiments, Johnson hypothesized that p75 is important for activating the feeding-promoting neurons within the hypothalamus.

“Inadequate regulation by neural circuits can lead to a variety of weight-related illnesses and disorders such as obesity and anorexia,” Johnson said. “Specifically, in obesity, people have trouble sensing hunger and limiting food intake. Greater understanding of these neural circuits can lead to more efficient dietary treatments and medications.”

Johnson has worked at Deppmann’s laboratory during the past three years. Initially, she worked on the metabolism team and currently, she is working with an M.D./Ph.D. student, Brandon Podyma, and a second-year undergraduate student.

Johnson was drawn to neuroscience because of her interest in the anatomy and function of the brain.

“Interacting with friends and family with a wide array of personality traits caused me to find the brain intriguing,” Johnson said. “I enjoy learning about how neural circuits interact to enable us to function. Neuroscience, which incorporates a variety of disciplines and integrates biology and psychology, presents exciting opportunities for innovative growth.”

Johnson, of Woodbridge, is hopeful the research could lead to better understanding of the neural circuits involved in mediating weight loss during a diet.

“Many people in society suffer from being extremely overweight or underweight,” she said. “If we know more about how neural circuits work together to regulate weight gain and loss, we can improve health negatively impacted by obesity.”

She also thinks the research could show more about the role of p75 in controlling metabolic homeostasis during diets.

“In the future, we plan to investigate the role of p75 in weight gain using a high-fat diet and [genetically modified subjects without] leptin, a peptide released from adipose tissue to signal the body to decrease food intake,” she said. “We want to know if p75 is acting in a similar way to its role in weight loss or a completely different way.”

Johnson has also learned to be flexible as she experiments.

“I have learned that unexpected results can be produced and some experiments can lead your project into a new direction,” she said. “My original award was to elucidate the sufficiency of p75 to resist weight loss in adipocytes, sympathetic and sensory nervous systems, but early in our experimentation, we realized p75 was not acting in those tissues. Then, we began analyzing the role of p75 in the central nervous system and have found very interesting results.”

An Echols Scholar and College Science Scholar, Johnson is a member of the Daniel Hale PreMed Honor Society; American Medical Student Association; the Undergraduate Research Network; OneWay InterVarsity Christian Fellowship; the Cavalier Symphony Orchestra; and is a Madison House volunteer for Medical Services. She has also participated in the Women’s Leadership Development Program and GradStar, an initiative to support African-American students’ academic excellence and to promote personal growth and involvement in all University activities and programs. A graduate of Osbourn Park High School and The Governor’s School at Innovation Park, she plans to pursue a medical degree and a Ph.D. to become a physician/scientist.

And through her work, Johnson has discovered persevering through the frustration of research.

“Research requires a lot of critical thinking,” Johnson said. “Although I love to succeed, research often results in many failures on the way to success. I have learned to accept failure, because it will eventually lead to success.”

By Matt Kelley, March 04, 2019
Reprinted from UVA Today

Filed Under: Media Highlights



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