A new study by scientists at the Massachusetts Institute of Technology and Harvard University has explored the complex relationship between nutrition, exercise, and the human body, and has come up with some pretty cool ideas. Research explores the cellular mechanisms of high-fat diets and physical activity, and how they may direct cells and body systems in healthy or unhealthy directions.
The new study stems from previous research by MIT researcher Manolis Kellis that focused on the region of the FTO gene, which is linked to fat mass and obesity risk. This previous work has shown how genes in this region regulate the signaling pathway that converts some types of immature fat cells into fat-burning or fat-storing cells.
Since then, Kellis has taken an interest in exercise to explore what kind of role it might play in the process. In collaboration with colleagues at MIT and Harvard Medical School, Kellis performed single-cell RNA sequencing on skeletal muscle tissue, white adipose tissue stacked around internal organs, and subcutaneous white adipose tissue under the skin.
These tissues were obtained from mice in four different experimental groups. Two groups of mice were fed either a normal diet or a high-fat diet for three weeks, and then these groups were divided into a stable group or an exercise group with the possibility of using a treadmill for another three weeks. Tissues from the four groups were then analyzed, enabling the scientists to determine which genes were activated or repressed by exercise in 53 different cell types.
“One of the general points that we found in our study, which is very clear, is how high-fat diets drive all of these cells and systems in one way, and exercise appears to drive nearly all of them in the opposite direction,” Kelis said. “She says exercise can have a huge impact all over the body.”
The analysis showed some interesting changes to occur, with stem cells known as mesenchymal stem cells (MSCs) at the center of many of them. These cells can differentiate into other cells such as fat cells or fibroblasts that connect tissues and organs, and scientists have found that a high-fat diet enhances their ability to differentiate into fat-storing cells. Conversely, exercise has been shown to reverse this effect.
Furthermore, the high-fat diet caused mesenchymal stem cells to secrete factors that alter the support structure around cells called the extracellular matrix. The matrix remodeling created a more inflammatory environment, and resulted in a new support structure that is more suitable for fat storage cells.
“When adipose cells (fat cells) become overburdened with fat, there is a great deal of stress, and that causes low-grade inflammation, which is systemic and maintained for a long time,” Kilis said. “This is one factor that contributes to the many negative effects of obesity.”
Increasingly, we are witnessing Research This reveals how the body’s clock, or circadian rhythm, can influence the metabolism and behavior of fat cells, and this new study is also relevant to this space. The authors found that high-fat diets suppress the genes that govern circadian rhythms, while exercise has the opposite effect and enhances them. Two of these genes were matched with human genes linked to circadian rhythms and an increased risk of obesity.
“There are a lot of studies showing that eating during the day is very important in how calories are absorbed,” said Kellys. “The correlation of circadian rhythm is very important, and shows how obesity and exercise actually directly affect circadian rhythms in peripheral organs, which can act systemically in distant clocks and regulate stem cell and immune functions.”
Scientists are now building on this work by analyzing samples from mice intestines, livers and brains to explore changes in those tissues, and collecting blood and tissue samples from people to investigate differences in human physiology. The authors consider the results as further evidence of how important a healthy diet and exercise are to our health.
But access to high-quality foods and the physical ability to exercise regularly are not taken for granted, nor are they viable lifestyle interventions for everyone. For this reason, the scientists believe the findings are also important in that they point to new targets for drugs that may one day replicate the effects of exercise.
“It is very important to understand the molecular mechanisms that lead to the beneficial effects of exercise and the harmful effects of a high-fat diet, so that we can understand how to intervene, and to develop drugs that mimic the effect of cross-training exercise,” Kilis said.
Publish the research in the journal cell metabolism.