Exercise and obesity have the opposite impact on muscle, fat tissues; researchers demonstrate

New insight into how excess belly fat may increase cancer risk

 Exercise training is a well-known means of maintaining and restoring good health; however, the molecular mechanisms underlying the benefits of exercise are not yet completely understood. A new paper by researchers at Joslin Diabetes Center in Cell Metabolismsheds light on the complex physiological response to exercise.

Taking advantage of recent single-cell technologies and advancements in computational biology, a team led by Laurie J. Goodyear, PhD, senior investigator of Integrative Physiology and Metabolism at Joslin Diabetes Center, launched a collaboration with a computational biology and artificial intelligence lab at Massachusetts Institute of Technology led by Manolis Kellis, PhD, to investigate how three metabolic tissues respond to exercise and to high-fat diet-induced obesity at single-cell resolution. These first-of-their-kind results provide a reference atlas of the single-cell changes induced by the exercise and obesity in two different types of fat and muscle. The investigators determined that there are opposite responses to exercise and obesity across all three tissues and highlight prominent molecular pathways modulated by exercise and obesity.

“Regular physical exercise is a well-established intervention for prevention and treatment of obesity and diabetes, and our goal is to set the foundation for understanding the molecular changes and cell types mediating the systemic effects of exercise and obesity in different tissues throughout the body,” said Goodyear, also a professor of medicine at Harvard Medical School. “The results of this study are going to serve as a tremendous resource that can lead to so much other work – not just from our laboratory but from other labs, too – that could eventually lead to the discovery of novel therapeutic options for obesity and other chronic metabolic diseases.”

Goodyear and colleagues focused the current investigation on two kinds of white adipose tissue – or fat – and skeletal muscle taken from mice which were either trained or sedentary, and fed either a healthful chow diet or fed a high-fat diet (HFD) intended to mimic the typical Western diet. This effectively provided four groups of mice; chow-fed/sedentary, chow-fed/active, HFD/sedentary and HFD/active. Diet treatments were for six weeks, and exercise training was done by housing mice with free access to a running wheel for three weeks.

After three weeks of the exercise intervention, the animals’ tissues were analyzed with single-cell RNA sequencing, providing the researchers with a plethora of new data. Among the most striking findings, the scientists observed that genes governing extracellular modelling (ECM) and circadian rhythm were regulated by both exercise and obesity across all three tissue types. Obesity up-regulated ECM-related pathways, while exercise down-regulated them. Conversely, exercise up-regulated circadian-related pathways, and obesity down-regulated them.

“With respect to the circadian rhythm, we saw very quiet cells that weren’t metabolically active with the high-fat diet group,” said co-first author Pasquale Nigro, PhD, a senior member of the Goodyear lab at Joslin and an instructor in medicine at Harvard Medical School. “We discovered that exercise reversed this. It seemed that, when the circadian system is upregulated, cells become re-activated.”

“As one of the most effective strategies to maintain a healthy body and mind, exercise is increasingly understood to induce tissue-specific and shared adaptations in the context of many other diseases beyond obesity,” said co-first author Maria Vamvini, MD, staff physician at Joslin and instructor in medicine at Harvard Medical School. “By combining our knowledge as physiologists with the computational biology skills of the Kellis lab at MIT, we’ve been able to develop a single-cell atlas with more than 200,000 cells and 53 annotated cell types. This resource has the potential to help our research team as well as others reveal fundamental exercise-induced changes in a diverse set of diseases and physiological contexts such as cancer and aging.  This teamwork stands out as a model for what we can accomplish through collaboration.”

Dogs with more active owners may get more exercise

A dog and its owner exercising together

Compared to inactive owners, active dog owners report exercising their dogs more and report their dogs’ weight as healthier CREDIT Diego Perez-Lopez, PLOS, CC-BY 4.0

A new, international study suggests that dog owners who spend more time exercising themselves tend to exercise their dogs more, and more active owners are also more likely to perceive their dog’s body weight as being ideal. Sydney Banton of the University of Guelph in Ontario, Canada, and colleagues present these findings in the open-access journal PLOS ONE on August 24, 2022.

Obese dogs may face a number of health problems, such as diabetes and cardiac disease, and concerns about dog obesity are increasing worldwide. Earlier research has identified associations between dogs’ body weight and diet, exercise, and sociodemographic factors. However, those studies tended to be small and focused on individual countries.

For a broader, international perspective, Banton and colleagues analyzed results from a survey of 3,298 dog owners living in France, Germany, the United Kingdom, Canada and the United States. The survey included questions about both owners’ and dogs’ diet and exercise routines, and each owner’s perception of their dog’s body weight.

Analysis of the survey responses showed that dogs were more likely to get more exercise if their owners spent more time exercising themselves. More active owners were also more likely to perceive their dog as having an ideal body weight. Compared to owners in other countries, owners in Germany tended to exercise their dogs for a longer time, were more likely to perceive their dog’s body weight as ideal, and were less likely to report having been told that their dog was overweight.

Among dogs who were 5 years old and older, owners were less likely to perceive their dog as having an ideal body weight if they had been told their dog was overweight, if they reported attempting to control their dog’s weight by limiting food intake, and if they reported giving dogs other foods, such as treats, every day.

The findings suggest that many owners may attempt to control dogs’ body weight through diet, but not through exercise. The researchers therefore call for veterinarians to be given more resources to help owners develop exercise routines to avoid weight gain in dogs.

Sydney Banton adds: “Results from the survey revealed that feeding practices play a main role in owner perception of their dog being overweight, while exercise practices play a main role in owner perception of their dog being an ideal weight. While many weight loss strategies for dogs focus on feeding, this data highlights the need to incorporate exercise into weight loss regimens.”

Survey finds nearly 1 in 5 Americans experience pain with exercise and continue to work out rather than resting to heal

Exam


George Eldayrie, MD, examines Jen Jordon at Orlando Health Jewett Orthopedic Institute. Jordon has had progressing knee pain over the past few years, and was relieved to hear that she did not need surgery and could help heal her injury by strengthening and stretching specific supporting muscles. CREDIT Orlando Health Jewett Orthopedic Institute

It’s not uncommon to have a lingering injury or nagging pain. In fact, a new national survey by Orlando Health finds nearly one in five Americans (18%) often experience pain while working out and the same number of people (18%) work through the pain rather than resting to heal.

Sports medicine physicians and orthopedic surgeons at the Orlando Health Jewett Orthopedic Institute say identifying the source of pain is the first step toward feeling better, and new advancements offer a range of options before surgery is part of the discussion. However, delaying treatment often leads to further damage and a higher likelihood that surgery will be needed to repair it.

“There’s the saying, ‘No pain, no gain.’ But there’s different types of pain that you feel during workouts, and sharp, stabbing pain that’s very uncomfortable is not typically normal,” said George Eldayrie, MD, a sports medicine physician at Orlando Health Jewett Orthopedic Institute. “The pain may be coming from an underlying problem and if you continue to push through it you can make that problem worse.”

Fitness class

Jen Jordon teaches a fitness class at the YMCA. Jordon finally addressed a lingering knee injury after years of progressing pain, something that’s very common according to a new national survey by Orlando Health that found nearly one in five Americans works out through pain rather than resting to heal. CREDIT Orlando Health Jewett Orthopedic Institute

Non-surgical options may include physical therapy to stretch and strengthen specific muscles and tendons. It may also involve injections that reduce inflammation and promote healing, such as corticosteroids and platelet-rich plasma, which are delivered precisely to the right area using ultrasound technology.

“Rehabilitation is a powerful tool, but it’s important to see a professional who can really key in on the right diagnosis so a therapist can develop a treatment plan focused to the right area,” saiid Dr. Eldayrie. “Platelet-rich plasma has also been shown to be very effective for chronic tendinopathies, things like tennis elbow or golfer’s elbow. But it typically works better the earlier it is administered, before the injury progresses.”

Jen Jordon, 39, lived with increasing pain in her left knee for years before finally making an appointment with Dr. Eldayrie to address it. 

“I would go into a lunge and just feel a sharp pain and then it would just continuously hurt throughout the day,” said Jordon. “It just kept getting a little bit worse and affecting me a little bit more during workouts and while I was on my feet at work, so I decided it was time to go get it checked out.”

Exercise is a daily part of Jordon’s life and something she relies on to maintain her physical and mental health. She put off treatment for fear she would be sidelined for a long period of time, or worse, would be told she needed surgery.

“Surgery is definitely a fear of mine. One of the reasons I work out is to stay healthy and prevent the need for surgery as I get older,” Jordon said. “Part of me didn’t really want to know what was going on because I didn’t want to have to take time off or have a procedure that was going to take weeks or months of recovery.”

Dr. Eldayrie examined Jen’s knee using x-rays and ultrasound to show her in real time where her tendons were strained and where degradation was occurring.  

“He was able to just point to the affected area and show me exactly what the issue was on his tablet. It was really informational and empowering to see the problem and learn how to take action to fix it,” Jordan said. 

Jen was also relieved to learn that she does not need surgery at this time, and will likely be able to solve her knee pain by adding exercises to better support the affected area. This will not only heal her knee, but also her fear of dealing with injuries.

“I am so glad that I went and had Dr. Eldayrie look at it, and I think it will help me prevent anything worse from happening in the future,” said Jordon. “After suffering for so many years and learning that simple stretching could have prevented the pain for all this time, I will definitely go in as soon as something starts hurting next time.” 

While there are a lot of non-surgical options, surgery is often the best course of action for injuries that require repair or reconstruction and will not heal on their own. However, that is not as scary as many patients believe. Advancements in robotic and laparoscopic procedures have made many surgeries less invasive and recovery shorter and easier than ever.

30-60 mins of weekly muscle-strengthening activity linked to 10-20% lower death risk

What is moderate and vigorous exercise?

Between 30 and 60 minutes of muscle-strengthening activity every week is linked to a 10-20% lower risk of death from all causes, and from cardiovascular disease, diabetes, and cancer, in particular, finds a pooled data analysis of the available evidence, published online in the British Journal of Sports Medicine.

The findings are independent of aerobic exercise. But the analysis points to a J-shaped curve for most outcomes, with no conclusive evidence that more than an hour a week of muscle-strengthening activity reduces the risk further still.

Physical activity guidelines recommend regular muscle-strengthening activities for adults, primarily because of the known benefits for skeletal muscle health. Examples of these activities include lifting weights; working with resistance bands; push-ups, sit-ups, and squats; and heavy gardening, such as digging and shovelling.

Previous research indicates that muscle-strengthening activity is associated with a lower risk of death, but it’s not known what the optimal ‘dose’ might be.

To try and find out, the researchers scoured research databases for relevant prospective observational studies that included adults without major health issues who had been monitored for at least 2 years.

The final analysis included 16 studies out of an initial cache of 29. The earliest study was published in 2012, and most studies were carried out in the USA, with the rest from England, Scotland, Australia, and Japan. The maximum monitoring period lasted 25 years.

Study participant numbers varied from nearly 4000 to almost 480,000, and ranged in age from 18 to 97. Twelve studies included both men and women; two included men only while three included women only. All the studies considered aerobic or other types of physical activity as well as muscle strengthening activities.

The pooled data analysis showed that muscle strengthening activities were associated with a 10–17% lower risk of death from any cause, as well as death from heart disease and stroke, cancer, diabetes, and lung cancer. 

No association was found between muscle strengthening and a reduced risk of specific types of cancer, including those of the bowel, kidney, bladder or pancreas. 

A J-shaped curve emerged, with a maximum risk reduction of between 10–20% at approximately 30–60 minutes/week of muscle strengthening activities for death from any cause, cardiovascular disease, and all cancer. 

An L-shaped association was observed for diabetes, with a large risk reduction up to 60 minutes/week of muscle strengthening activities, after which there was a gradual tapering off. 

Joint analysis of muscle strengthening and aerobic activities showed that the reduction in risk of death from any cause, cardiovascular disease, and cancer was even greater when these two types of activities were combined: 40%, 46%, and 28% lower, respectively. 

The researchers acknowledge certain limitations to their findings, the main one of which was that data from only a few studies were pooled for each of the outcomes studied. The included studies also relied on subjective assessment of muscle strengthening activities.

Because most of the studies were carried out in the US, the results might not be more widely applicable, caution the researchers, who add that the included studies were all observational rather than clinical trials.

Given the J-shaped associations, the potential of a higher volume of muscle strengthening activities on the reduction in risk of death is unclear, they write. 

But they conclude: “The combination of muscle strengthening and aerobic activities may provide a greater benefit for reducing all-cause, [cardiovascular disease], and total cancer mortality. 

“Given that the available data are limited, further studies—such as studies focusing on a more diverse population—are needed to increase the certainty of the evidence.”

Walkable neighborhoods can reduce prevalence of obesity, diabetes


People who live in walkable neighborhoods with access to parks and other outdoor activities are more active and less likely to have diabetes or obesity, according to a new paper published in the Endocrine Society’s journal, Endocrine Reviews.

Nearly half of the adults in the United States have obesity, and over 11 percent of the U.S. population has diabetes. Researchers and policymakers have been searching for an effective way to promote healthy lifestyles at a population level to address these dual epidemics.

The built environment is the manmade structures that provide people with living, working and recreational spaces. This environment includes buildings, neighborhoods, parks, bike paths, restaurants, shops, roads and public transportation. Human health is affected by the physical environments we construct.

“The built environment can influence physical activity levels by promoting active forms of transportation, such as walking and cycling over passive ones, such as car use,” said Gillian L. Booth, M.D., M.Sc., of the University of Toronto, St. Michael’s Hospital of Unity Health Toronto and ICES in Ontario, Canada. “Shifting the transportation choices of local residents may mean that more members of the population can participate in physical activity during their daily routine without structured exercise programs.”

The researchers reviewed several studies on the built environment and their effects on public health and found walkable, activity-friendly cities and neighborhoods were associated with a lower risk of obesity and diabetes. One large population-based study of 32,767 people found the prevalence of obesity among adults living in highly walkable neighborhoods compared to those living in low walkability areas was 43% vs. 53%.

A study of 1.1 million adults with normal blood sugar levels found the incidence of pre-diabetes was 20% higher among people living in less walkable areas after 8 years of follow up. Another study of 1.6 million adults found a 30% to 50% higher likelihood of developing diabetes among people living in low versus highly walkable areas. In a population-based Canadian study, moving from an unwalkable to a highly walkable neighborhood was associated with a 54% lower likelihood of being diagnosed with high blood pressure.

The paper also noted that air pollution and high concentrations of fast-food restaurants are risk factors for diabetes and can substantially reduce the benefits of living in a walkable neighborhood.

“We need policies that promote healthier eating habits and opportunities to engage in active forms of transportation,” said Booth. “Designing neighborhoods that have safe and effective public transit options, cycling infrastructure and walking paths may reduce traffic related pollution.”