American Heart Association funds research into how obesity affects sugar metabolism

Feb 27, 2019

Leslie Consitt, Ph.D.

Leslie Consitt, Ph.D., associate professor of biomedical sciences at the Ohio University Heritage College of Osteopathic Medicine, has received a two-year, $154,000 award from the American Heart Association for a research project to investigate how obesity may impair the body’s ability to metabolize sugar.

It is hoped that the findings of the study will be useful in designing therapeutic strategies to regulate skeletal muscle metabolism and ultimately help prevent obesity and its attendant problems of cardiovascular disease, stroke and type 2 diabetes. The study was already gathering data prior to the award; the AHA funding will allow for recruitment of more study subjects and for data analysis.

“Consumption of sugar is a daily occurrence for many,” Consitt notes. “However, the resulting hyperglycemia, or elevated blood sugar, commonly observed in obese individuals puts them at increased risk for diabetes and heart disease.” Recent data show that despite the known negative health effects, more than 50 percent of Americans continue to drink at least one “sugar beverage” a day.

“Dr. Consitt’s work builds on our college’s commitment to diabetes-related research and could have significant implications for populations at risk for cardiovascular disease,” said Darlene Berryman, Ph.D., R.D., L.D., associate dean for research and innovation at the Heritage College. “While many of us appreciate the need to limit dietary sugar, her research could establish the underlying mechanism responsible for the negative effects of excess sugar on health. And importantly, Dr. Consitt’s research is truly translational – bridging her expertise in the basic sciences and in clinical research to both educate the public and improve health outcomes.”

Does obesity impair the body’s burning of sugar?

Consitt’s AHA-funded study will explore mechanisms that could be responsible for causing elevated blood sugar in obese individuals after they drink a glucose beverage. It will investigate whether obesity blunts the body’s ability to oxidize (burn) sugar at the whole-body level – that is, in multiple organs – and if so, what cellular mechanisms might cause this result.

The subject of the research is a phenomenon called “metabolic inflexibility,” which is an organism’s inability to efficiently adjust its fuel-oxidizing rates to match the amount of dietary fuel, such as sugar, that’s available to the body. Metabolic inflexibility is believed to play a key role in obesity, but scientists don’t know what mechanisms at the cellular level account for it.

Consitt’s study will compare the cellular pathways responsible for glucose metabolism between lean, healthy individuals and obese individuals in response to a high-glucose drink. The research will be looking for changes that take place in skeletal muscle, which is the main organ in the body responsible for taking up glucose from the bloodstream. Consitt will seek to identify possible obesity-related changes in both insulin signaling and in the activation of an enzyme called pyruvate dehydrogenase (PDH).

Looking at insulin signaling, and a key enzyme’s role

The uptake of glucose by skeletal muscle requires insulin, which is secreted by the pancreas. Insulin binds to the muscle and activates a number of proteins that allow glucose to enter the muscle; this process is called the insulin signaling pathway. Consitt’s research will investigate whether this signaling is somehow impaired in obese individuals, interfering with glucose uptake by muscle and leading to higher levels of sugar in the blood.

This will be determined by taking a muscle biopsy first when the test subject is fasting and again 50 minutes after the person drinks a glucose beverage – at a time when insulin signaling should be at its maximum level in a healthy individual. The Clinical and Translational Research Unit (CTRU) at the Heritage College will assist in conducting the study.

The study will also look at whether obesity correlates to changes in PDH activation. Once glucose is taken up by muscle, it can be burned as fuel inside the mitochondria, the powerhouse of the cell. PDH is the key enzyme that allows glucose to enter the mitochondria. Researchers suspect that people with obesity suffer from impaired glucose oxidation, and Consitt’s study will try to ascertain whether this results from a reduced ability to activate PDH.

To answer this question, researchers will compare what PDH activity looks like while the subject is fasting to what it looks like 50 minutes after drinking a glucose beverage.

Collaborative research that benefits science, students and community

Consitt’s research proposal suggests that the project’s findings “will provide a framework for researchers and health professions to design effective and targeted therapeutic strategies to regulate skeletal muscle metabolism, and ultimately help lead to building healthier lives, free of cardiovascular diseases, stroke and type 2 diabetes.” Another outcome of the research could be better identification of the unhealthy impacts of drinking sugary beverages.

Consitt said she believes the study will help spread the word about the risk factors for cardiovascular disease and type 2 diabetes, both through the participation of area residents as research subjects and through community forums publicizing the research findings. “The funding of this project will assist with the growth of translational obesity/diabetes research at OHIO and within the Heritage College,” she predicted. “This project will also provide the opportunity for students to have hands-on experience, learning both clinical and basic science skills.”

She added that the research community will also benefit from her findings, which will “fill a gap in knowledge regarding the cellular impact of sugar on muscle. Identifying cellular impairments in the muscle should lead to more effective treatment and preventive programs.”

Collaborating on the project are CTRU research nurses Cammie Starner, R.N., and Lynn Petrik, B.S.N., R.N., who will perform blood draws, and Timothy Law, D.O. (’94), M.B.A., medical director for the Ohio Musculoskeletal & Neurological Institute (OMNI), who will perform muscle biopsies. Ohio University undergraduates Eric Weir from the College of Health Sciences and Professions and Courtney Dudley from the Department of Biological Sciences currently work on the project, and OHIO alumni Dominic Maschari (CHSP) and Erin Walsh and Alicson Saneda (biological sciences) previously served on the research team. Brian Clark, Ph.D., professor of physiology and neuroscience, executive director of OMNI and holder of the Osteopathic Heritage Foundation Harold E. Clybourne, D.O., Endowed Research Chair, has helped with statistics.

Consitt is currently analyzing data already collected from study volunteers, but may begin recruiting participants again later this spring from Ohio University and southeast Ohio. A previous research project of Consitt’s, investigating links between the protein myostatin and insulin resistance, was awarded funding from the National Institutes of Health.