Cell Metabolism: Exercise and obesity have opposite effects on muscle and adipose tissue

Athletic training is a well-known method of maintaining and restoring health; However, the molecular mechanisms
of the benefits of exercise are not yet fully understood.
A new paper by researchers at the Jocelyn Diabetes Center for Cell Metabolism elucidates the complex physiological response
to exercise.

Using recent advances in single-cell technology and computational biology, the team, led by Dr.
Laurie J.
Goodyear, a senior fellow in integrative physiology and metabolism at the Jocelyn Diabetes Center, collaborated with MIT's Computational Biology and Artificial Intelligence Laboratory, led by Dr.
Manolis Kellis, to study the response of three metabolic tissues
to exercise and high-fat diet-induced obesity with single-cell resolution.
These unprecedented results provide a reference map
of the single-cell changes caused by exercise and obesity in two different types of fat and muscle.
The researchers determined that these three tissues responded to exercise and obesity in opposite ways, and highlighted prominent molecular pathways
regulated by exercise and obesity.

"Regular physical activity is a proven intervention to prevent and treat obesity and diabetes, and our goal is to lay the foundation for understanding the molecular changes and cell types that exercise and obesity mediate systematically in different tissues throughout the body," said
Goodyear, a professor of medicine at Harvard Medical School.
"The results of this study will be a huge resource that could lead to a lot of other work – not just our labs, but also other labs – that may eventually discover new treatments
for obesity and other chronic metabolic diseases.
"

Goodyear's and his colleagues' current research focused on two types of white fatty tissue (or fat) and skeletal muscle taken from trained or sedentary mice that either ate healthy foods or ate fatty foods (HFDs)
that mimic the typical Western diet.
This effectively provides four groups of mice; Eat more/sedentary, eat more/be active, eat a high-calorie diet/sedentary diet/be and a high-calorie diet/be active
.
Diet therapy lasts six weeks, and exercise training places mice on a free-walking wheel for three weeks
.

After three weeks of exercise intervention, the researchers performed a single-cell RNA sequencing analysis of the animals' tissues, providing researchers with a wealth of new data
.
Among the most astonishing findings, the scientists observed that genes that control extracellular modeling (ECM) and circadian rhythms are regulated
by exercise and obesity in all three tissue types.
Obesity upregulated ecm-related pathways, while exercise downregulated them
.
Instead, exercise upregulated the pathways associated with circadian rhythms, while obesity downregulated these pathways
.

"Regarding circadian rhythms, we saw very quiet cells with inactive metabolism in the high-fat diet group," said co-first author Dr.
Pasquale Nigro, a senior member of Joslin Goodyear's lab and a medical lecturer
at Harvard Medical School.
"We found that exercise can reverse that
.
It seems that when the circadian system is up-regulated, the cells are reactivated
.
”

"As one of the most effective strategies for maintaining physical and mental health, there is a growing recognition that exercise can induce tissue specificity and shared adaptability in the context of many other diseases other than obesity," said
co-first author Maria Vamvini, Ph.
D.
, attending physician at Jocelyn Hospital and medical lecturer at Harvard Medical School.
"By combining the knowledge of our physiologists with the computational biology skills of MIT's Kellies lab, we have been able to develop a single-cell atlas
containing more than 200,000 cells and 53 annotated cell types.
" This resource has the potential to help our research team, as well as others, uncover fundamental changes
caused by exercise in a variety of diseases and physiological settings, such as cancer and aging.
This teamwork is an example
of how we achieve our goals through cooperation.
”

Single-cell dissection of the obesity-exercise axis in adipose-muscle tissues implies a critical role for mesenchymal stem cells