Scientists have charted how exercise affects the body

Exercise is known to help people lose weight and avoid weight gain

In a new study of mice, researchers at MIT and Harvard Medical School mapped out many of the cellular, genetic, and cellular pathways altered by exercise or high-fat diets, expanding researchers' understanding of

Manolis Kellis, a professor of computer science at MIT's Computer Science and Artificial Intelligence Laboratory (CSAIL) and a member of MIT and Harvard, said: "It is extremely important to understand the molecular mechanisms that drive the beneficial effects of exercise and the harmful effects of fatty diets so that we can understand how to intervene, And developed drugs that simulate the effects of motion on a variety of tissues

The researchers studied mice on a high-fat or normal diet that were either sedentary or had the opportunity to exercise

"One of the basic ideas we found in our research is how a high-fat diet pushes all of these cells and systems in one direction, and movement seems to be how to propel almost all of these cells and systems in the opposite direction," Kellies said

Laurie Goodyear, a professor of medicine at Harvard Medical School and a senior fellow at the Jocelyn Diabetes Center, is the senior author of the study, published today in the journal Cell Metabolism

Risk of obesity

Obesity is a growing health problem

"Obesity and aging are global factors that affect every aspect of human health," Kellies said

A few years ago, his lab conducted a study of the FTO gene region, which is closely linked to

The finding suggests that obesity has a distinct genetic component, which prompted Kellies to begin studying how exercise acts on progenitor fat cells at the

To explore this question, Kellis and his colleagues decided to sequence single-cell RNA on three tissues — skeletal muscle, visceral white adipose tissue (which gathers around internal organs where fat is stored), and subcutaneous white adipose tissue (found under the skin and primarily burns fat).

These tissues come from mice

By analyzing the tissues of these mice, the researchers were able to comprehensively classify

The researchers found that in all three tissue types, mesenchymal stem cells (MSCs) appeared to control many of the diet- and exercise-induced effects

In addition to promoting fat storage, the researchers found that high-fat diets also stimulate MSCs to secrete factors that reshape the extracellular matrix (ECM)—a network

Kellies said: "When fat cells are overloaded with lipids, they produce a lot of stress, which leads to low-level inflammation, which is systemic and lasts for a long time

Physiological effects

The researchers also found that a high-fat diet and exercise had the opposite effect on
the cellular pathways that control circadian rhythms.
Circadian rhythm is a 24-hour cycle that controls many functions, from sleep to body temperature, hormone release, and digestion
.
Studies have shown that exercise promotes the expression of genes that regulate these rhythms, while a high-fat diet suppresses the expression
of these genes.

"There's a lot of research that shows that when you eat during the day is very important to how you absorb calories," Kellies said
.
"The link between circadian rhythms is very important and shows how obesity and exercise actually directly affect the circadian rhythms of peripheral organs, which may have a systematic effect on the distal clock and regulate stem cell function and immunity
.
"

The researchers then compared
their results with a database of human genes associated with metabolic traits.
They found that the two circadian gene found in this study, DBP and CDKN1A, have genetic variants
associated with a higher risk of obesity in humans.

"These results help us see the translational value of these targets and how we can potentially target specific biological processes
in specific cell types," Yang said.

The researchers are now analyzing samples of small intestine, liver and brain tissue from mice in the study to explore the effects of exercise and a high-fat diet on these tissues
.
They also worked with human volunteers to sample blood and living tissue and study similarities and differences
in human and mouse physiology.
They hope their findings will help guide drug developers in designing drugs
that might mimic some of the beneficial effects of exercise.

"The message to everyone should be, if possible, eat a healthy diet and exercise," Kellies said
.
"For those who can't do that because they rarely have access to healthy food, disability or other factors that hinder exercise, or simply lack the time to have a healthy diet or a healthy lifestyle, this study shows that we are now better at dealing with pathways, specific genes, specific molecular and cellular processes that we should treat
.
"

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