A new study by researchers at MIT and Harvard Medical School maps many cells, genes and cellular pathways that are changed by Exercise or a high-fat diet, shedding light on exactly how exercise can help prevent obesity.

Scientists studied mice fed high-fat or normal diets; in each case, some mice were sedentary and others allowed to exercise. Using single-cell RNA sequencing, they cataloged gene expression changes in 53 cell types found in skeletal muscle and two types of adipose tissue.

In all three tissue types, mesenchymal stem cells (MSCs), which can differentiate into fat cells and fibroblasts, appeared to control many of the observed effects. A high-fat diet enhanced the ability of MSCs to turn into fat storage cells, stimulated them to secrete factors that structure enlarged fat cells, and created a more inflammatory environment. Exercise reversed these effects.

The study also showed that exercise stimulates the expression of MSC genes that regulate circadian rhythms, while a high-fat diet suppresses them. These included genes linked to different obesity risks in humans.

“It is extremely important to understand the molecular mechanisms that drive the beneficial effects of exercise and the detrimental effects of a high-fat diet, so that we can understand how we can intervene,” says Professor Manolis Kellis ’99, MEng ’99, PhD ’03, one of the study’s lead authors.

Tech