COLUMBUS, Ohio – Many health care facilities worldwide prescribe preoperative exercise therapy to improve patients' surgical outcomes. A new mouse study led by researchers at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James), The Ohio State University Wexner Medical Center and College of Medicine sheds light on the mechanisms underlying the protective effect of preoperative exercise on surgically induced liver injury.

Study findings are published online in the journal Nature Metabolism.

Pre-operative exercise therapy has been shown to improve outcomes for many patients who undergo surgery, yet the mechanisms by which pre-operative exercise protects the organ from inflammatory injury are unclear.

Ohio State researchers have been studying the mechanisms underlying an inadequate blood supply to an organ, also known as ischemia, and the tissue damage caused when blood supply returns to tissue, also known as reperfusion injury. This type of injury often occurs during liver surgery.

“We believe this is a major finding. Understanding the underlying molecular mechanisms will allow us to precisely design the preoperative therapy for exercise-tolerant patients that will train innate immune cells to modulate inflammatory responses,” said study co-corresponding author Dr. Meihong Deng, associate professor in the Division of Trauma, Critical Care and Burn in Ohio State’s Department of Surgery.

The study found that a four-week aerobic pre-operative exercise regimen significantly reduces liver injury and inflammation from ischemia and reperfusion in mice. Importantly, these beneficial effects lasted for seven more days after completing pre-operative exercise.

The study shows that the exercise specifically drives Kupffer cells toward an anti-inflammatory phenotype with trained immunity via metabolic reprogramming. Kupffer cells are a type of cell that form the lining of small irregularly shaped blood vessels found in the liver called sinusoids that are involved in the breakdown of red blood cells.

“These findings provide molecular and cellular targets that can be exploited pharmaceutically to develop new preoperative exercise, mimicking strategies for exercise-intolerant patients,” said study co-corresponding author Dr. Allan Tsung, director of the Division of Surgical Oncology at the OSUCCC – James, whose research focuses on focuses on surgery-triggered immune responses in liver metastases.

The research team included members of Ohio State Wexner Medical Center’s Department of Surgery and Division of Hematology and the Department of Microbial Infection and Immunity at Ohio State’s Infectious Disease Institute. Other researcher collaborators were from the University of Pittsburgh; Huazhong University of Science and Technology in Wuhan, China; and Beth Israel Deaconess Medical Center in Boston.

“Our research groups have intensively studied the molecular mechanisms underlying liver ischemia and reperfusion injury. Future research will involve collecting samples from preoperative exercise patients to further study these mechanisms in clinical settings,” said lead corresponding author Dr. Hai Huang, an assistant professor of surgical oncology and a researcher in the Translational Therapeutics Program at OSUCCC – James.

This research was supported by grants from the National Institutes of Health.

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Media Contact: Eileen Scahill
Wexner Medical Center Media Relations
614-293-3737
Eileen.Scahill@osumc.edu