Michael Hunter, MD on Medika Life

Obesity and Exercise Have Opposite Effects on Muscle and Fat

A NEW STUDY SHEDS LIGHT ON THE PHYSIOLOGICAL RESPONSE TO EXERCISE. Physical activity is an important tool for maintaining or restoring good health. The new research provides insights into the molecular mechanisms underlying exercise-related health improvements. We’ll look at the basic science of how obesity and exercise affect muscle and fat.

Get regular physical activity, and you can reduce your risk of becoming obese, developing diabetes, suffering from cardiovascular disease, dodge particular cancers, and more. But how does exercise work its physiological magic?

First, we’ll review some of the health benefits of regular physical activity. Second, we’ll turn to a new study that sheds light on how moving affects our physiology at a basic level.

Physical activity and cardiovascular disease

Many of us lead sedentary lifestyles, at least in the United States. Unfortunately, not getting regular physical activity is an independent risk factor for the early development of coronary heart disease.

Unfortunately, much of the evidence supporting the risk-reducing properties of exercise comes from long-term observational studies that demonstrate this:

Those who get regular physical activity have much less coronary heart disease and a lower risk of experiencing cardiac arrest.

Photo by Sébastien Goldberg on Unsplash

Let’s compare the least active among us with the most active. I live in King County, Washington (USA). There, researchers from the University of Washington performed a population-based case-control study to examine the associations between regular high-intensity and moderate-intensity leisure-time physical activity and primary cardiac arrest.

The investigators looked at 333 patients with primary cardiac arrest, aged 25 to 75, attended by paramedics. Controls were randomly selected from the same community and matched for age and sex. None of the subjects had a history of heart disease, major health problems, or self-reported poor health.

The researchers interviewed partners of patients and controls to assess participation in 15 high-intensity and six moderate-intensity physical activities during the previous year.

Here are the relative risk reductions by activity type:

  • Gardening for more than 60 minutes per week appeared to be associated with a drop in risk by two-thirds.
  • Walking for exercise for more than 60 minutes per week appeared to be associated with a nearly three-quarters risk reduction.
  • Engaging in high-intensity activities appeared to be associated with a drop in risk by two-thirds.

Unfortunately, I did not see absolute risk reduction numbers. However, here is some context: Globally, cardiac arrest takes more lives than colorectal cancer, breast cancer, prostate cancer, influenza, pneumonia, auto accidents, HIV, firearms, and house fires combined. In one year alone, 350,000 Americans die from cardiac arrest.

A sedentary lifestyle is an independent risk factor for cardiac arrest. Of course, exercise is not completely free of potential perils. Physical activity can have rare adverse effects, including heart attack, heart rhythm problems, sudden death, and rhabdomyolysis.

Rhabdo happens when damaged muscle tissue releases its proteins and electrolytes into the blood. These substances can damage the kidneys and heart and lead to permanent disability or even death.

Physical activity and weight

Exercise is important to prevent obesity; sedentary behavior is associated with weight gain. For older or obese adults, higher activity levels (compared to young adults) appear necessary to prevent weight gain.

study of 34,000 females (with an average age of 54) consuming a usual diet had an average weight gain of 2.6 kilograms (5.7 pounds) over 13 years.

Compared with females doing more than 420 minutes per week of exercise (an average of one hour daily), those engaging in less activity gained significantly more weight.

Physical activity appeared inversely related to weight gain only among normal-weight individuals. To maintain normal body weight in mid-life, the females in the study needed higher levels of physical activity (about 60 minutes daily).

Photo by Diana Polekhina on Unsplash

Once overweight, physical activity alone (without controlling caloric intake) did not prevent weight gain.

The available research findings suggest that physical activity protects against obesity regardless of an individual’s genetic predisposition to it.

Physical activity and life expectancy

Physical inactivity is associated with a reduced life expectancy. A retrospective study published in JAMA addresses this issue. The study explores the link between long-term mortality and various levels of cardiorespiratory fitness.

Cardiorespiratory fitness measures how well your heart and lungs pump blood and oxygen during prolonged exercise. The more fit you are, the higher your cardiorespiratory fitness.

Over 122,000 patients at the Cleveland Clinic (USA) had exercise testing on a treadmill to measure cardiorespiratory fitness for the research investigation. The subjects ranged in age from 18 to over 80, with an average age of 53. The results?

Cardiorespiratory fitness appeared to be associated with living longer. The higher the fitness, the higher the survival rate, regardless of age. The connection appeared to be especially strong among older individuals and those with high blood pressure. Moreover, the survival benefit continued to increase with no upper limit.

Physical activity — How it works its magic

Physical activity is a wonderful way to help maintain and restore good health. Despite numerous studies demonstrating this relationship, the molecular mechanisms underlying the benefits remain incompletely elucidated.

new paper by researchers at Harvard Medical School (USA) and Massachusetts Institute of Technology (USA) in Cell Metabolism illuminates the complex physiological response to exercise.

The Harvard/MIT team combined modern single-cell technologies with advanced computational biology and artificial intelligence to look at how three metabolic tissues respond to exercise and high-fat diet-induced obesity at a single-cell resolution. This project is a first-of-its-kind research investigation.

The researchers discovered opposite responses to exercise and obesity across all three tissues.

Goodyear and colleagues focused on three tissues, including two kinds of white adipose tissue (fat) and skeletal muscle taken from mice. The rodents were either trained or sedentary and consumed either a healthy or high-fat diet (the latter aiming to mimic a typical Western diet).

Here are the four mice groups:

  • Regular diet/sedentary
  • Regular diet/active
  • High-fat diet/sedentary
  • High-fat diet/active

The mice consumed the diet for six weeks. The active mice had free access to a running wheel for three weeks.

Photo by Ricky Kharawala on Unsplash

After three weeks of exercise, researchers used single-cell RNA sequencing. Here are the findings:

Genes regulating extracellular matrix* remodeling and circadian rhythm appeared to be regulated by exercise and obesity in all three tissue types. Obesity up-regulated extracellular modeling, while exercise down-regulated them. Conversely, exercise up-regulated circadian-related pathways, and obesity down-regulated them.

  • The extracellular matrix is the “non-cellular portion of a tissue. It is a collection of extracellular material produced and secreted by cells into the surrounding medium. The extracellular matrix provides structural and biochemical support to the surrounding cells.”

Here is co-first author, Pasquale Nigro, Ph.D.:

“With respect to the circadian rhythm, we saw very quiet cells that weren’t metabolically active with the high-fat diet group. We discovered that exercise reversed this. It seemed that, when the circadian system is up-regulated, cells become re-activated.”

My take — Physical activity

Unless there is a medical contraindication, we should all try to achieve and maintain high fitness levels.

Current guidelines recommend 150 to 300 minutes per week of moderate aerobic activity (such as walking, running, swimming, or biking), 75 minutes of vigorous activity, or a mix of both. Experts also recommend twice-weekly resistance training to strengthen muscles.

Unfortunately, only about one in five adults and teens in the United States gets enough exercise to maintain good health. We can do better.

Thank you for joining me in this look at the effects of obesity and exercise on fat and muscle.


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Michael Hunter, MD
Michael Hunter, MD
I received an undergraduate degree from Harvard, a medical degree from Yale, and trained in radiation oncology at the University of Pennsylvania. I practice radiation oncology in the Seattle area.

Michael Hunter, MD

I received an undergraduate degree from Harvard, a medical degree from Yale, and trained in radiation oncology at the University of Pennsylvania. I practice radiation oncology in the Seattle area.

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