Exercise is well-known to help people lose weight and avoid gaining it. However, identifying the cellular mechanisms that underlie this process has proven difficult because so many cells and tissues are involved.
In a new study in mice that expands researchers’ understanding of how exercise and diet affect the body, MIT and Harvard Medical School researchers have mapped out many of the cells, genes, and cellular pathways that are modified by exercise or high-fat diet. The findings could offer potential targets for drugs that could help to enhance or mimic the benefits of exercise, the researchers say.
“It is extremely important to understand the molecular mechanisms that are drivers of the beneficial effects of exercise and the detrimental effects of a high-fat diet, so that we can understand how we can intervene, and develop drugs that mimic the impact of exercise across multiple tissues,” says Manolis Kellis, a professor of computer science in MIT’s Computer Science and Artificial Intelligence Laboratory (CSAIL) and a member of the Broad Institute of MIT and Harvard.
The researchers studied mice with high-fat or normal diets, who were either sedentary or given the opportunity to exercise whenever they wanted. Using single-cell RNA sequencing, the researchers cataloged the responses of 53 types of cells found in skeletal muscle and two types of fatty tissue.
“One of the general points that we found in our study, which is overwhelmingly clear, is how high-fat diets push all of these cells and systems in one way, and exercise seems to be pushing them nearly all in the opposite way,” Kellis says. “It says that exercise can really have a major effect throughout the body.”
Kellis and Laurie Goodyear, a professor of medicine at Harvard Medical School and senior investigator at the Joslin Diabetes Center, are the senior authors of the study, which appears today in the journal Cell Metabolism. Jiekun Yang, a research scientist in MIT CSAIL; Maria Vamvini, an instructor of medicine at the Joslin Diabetes Center; and Pasquale Nigro, an instructor of medicine at the Joslin Diabetes Center, are the lead authors of the paper.
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