Tag Archives: exercise

PHD3 Loss, Fat Metabolism, and Exercise Endurance

October 1, 2020

Tolerance of exercise and endurance can both decrease with age and declining metabolic health yet physical activity remains a cornerstone of physical and mental health regardless of age. Enzyme systems have received increasing attention for their potential to reduce exercise fatigue and improve endurance by providing the body with access to energy reserves and optimizing their use. Sugars are the primary fuel of cellular processes however, when nutrients are scarce – such as in cases of starvation or extreme exertion – cells switch to breaking down fats for energy. At this time, the mechanisms behind the rewiring of cellular metabolic pathways in response to fluctuations in resource availability are poorly understood.

New research published earlier this month in Cell Metabolism suggests a surprising consequence when one such mechanism is turned off – an increased capacity for endurance exercise. Recently conducted by researchers from the Harvard Medical School, the study revealed that blocking the activity of a fat-regulating enzyme in the muscles of mice could lead to an increased capacity for endurance exercise

Boosting Exercise Endurance in Mice

Led by Marcia Haigis, professor of cell biology at Harvard Medical School, a team of researchers investigated the function of the enzyme prolyl hydroxylase 3 (PHD3) – which they believed played a role in regulating fat metabolism in certain cancers. The study’s authors investigated the impact of PHD3 inhibition in genetically modified mice by carrying out a series of endurance exercise experiments.

Under normal conditions, PHD3 chemically modifies the enzyme ACC2 which prevents fatty acids from entering mitochondria to be broken down into energy. The team of researchers found that blocking PHD3 production in mice resulted in dramatic improvements in fitness measures: mice lacking the PHD3 enzyme ran 40% longer and 50% farther on treadmills and had a higher VO2 max – indicating increased aerobic endurance – than control subjects.

After endurance experiments, the muscles of PHD3-deficient mice revealed heightened rates of fat metabolism and an altered fatty acid composition and metabolic profile. According to the authors, their findings held true in genetically modified mice demonstrating that PHD3 loss in muscle tissues may be sufficient to boost exercise capacity.

PHD3 Enzyme Regulates Metabolic Pathways

After performing a series of molecular analyses to detail precise molecular interactions allowing PHD3 to modify ACC2 and how its activity repressed by AMPK, Haigis and her team reported that PHD3 and AMPK, another enzyme, simultaneously control the activity of ACC2 to regulate fat metabolism depending on energy resource availability.

Their research identified the critical role of the enzyme prolyl hydroxylase 3 (PHD3) in sensing nutrient availability and regulating the ability of muscle cells to metabolize fats, revealing that when nutrients are abundant, PHD3 acts as a brake inhibiting unnecessary fat metabolism that is released during exercise. Whole body or skeletal muscle PHD3 loss enhances acute exercise capacity during endurance exercise experiments.

“The findings shed light on a key mechanism for how cells metabolize fuels and offer clues toward a better understanding of muscle function and fitness,” the authors wrote.

“Understanding this pathway and how our cells metabolize energy and fuels potentially has broad applications in biology, ranging from cancer control to exercise physiology,” senior author Haigis explained. Although, further research is needed to identify whether this pathway can be manipulated in humans to improve muscle function, in the treatment of various diseases, and to better understand how PHD3 inhibition improves exercise capacity.

The latest findings carry implications for a potential novel approach to enhancing exercise performance, treating muscle disorders, as well as developing therapeutic methods for certain cancers in which mutated cells express decreased levels of PHD3. At this time, whether there are any negative effects – including weight loss, blood sugar changes and other metabolic markers – associated with PHD3 loss remains unknown although, this will hopefully be elucidated by future research.

Exercise as a Treatment for Depression

July 12, 2018

An extensive body of research throughout the past decade indicates that exercise may be an effective treatment for depression, and could potentially act as a preventive measure against depression. Outcomes from research, and a 2016 pool of studies involving over one million men and women, strongly suggest that regular exercise can not only alter our bodies, but also transform the brain so that the resistance to despair & depression is heightened and increased.

For many years, scientists have investigated the correlation between physical activity and mental health. While it has long been understood that exercise alters the body, how physical activity affects emotional health is less clear: some randomized controlled trials have found that exercise programs ease symptoms in people with major depression.

A group of global researchers in public health, however, has worked to further support the case for exercise as a treatment for–and preventive measure against–depression. For the newer analyses, they initially gathered all of the most recent and most well-designed studies surrounding depression and exercise. The ‘most innovative’ of the new studies, published in 2016 in Preventive Medicine, focused on whether exercise could help to prevent the development of depression.

Due to the frequent unreliability of how we report our exercise and workouts, the researchers solely utilized past studies that had “objectively measured participants’ aerobic fitness,” which will rise or fall depending on whether and how much someone exercises. Other parameters for the study included a measurement of participants’ mental health, at both the initial outset and conclusion of the study, coupled with follow-up time of at least a year.

The researchers found several large-scale past studies that met their criteria, which collectively contained data on more than 1,140,000 adult men and women. Among these million-plus people, the links between mental health and fitness was fairly strong. When the researchers divided the group into thirds, based on their respective aerobic fitness, those men and women with the lowest fitness were about 75 percent more likely to have been given diagnoses of depression than the people with the greatest fitness. The men and women in the middle third were almost 25 percent more likely to develop depression than those who were the most fit.

In a separate study (some of the scientists were involved in each of the reviews), researchers looked at whether exercise might be useful as a treatment for depression. In that analysis, which was published in Journal of Psychiatric Research in June 2016, they pooled data from 25 past studies in which people with clinically diagnosed depression began some type of exercise program. The pooled results demonstrated that exercise, specifically a moderately strenuous workout such as brisk walking or jogging, has a “large and significant effect” against depression. People’s mental health tended to improve considerably if they were physically active. The final review further clarifies reasons as to why this may be true. Published in Neuroscience & Biobehavioral Reviews in February 2016, it sought to understand what happens to the body during and after exercise that might impact and enhance mood. The researchers analyzed 20 previous studies, all of which included results from blood samples from people with major depression before and after they had exercised. Overall, the findings in the samples indicated that exercise “significantly reduced various markers of inflammation and increased levels of a number of different hormones and other biochemicals that are thought to contribute to brain health.”

As reported in The New York Times, Felipe Barreto Schuch, an exercise scientist at the Centro Universitário La Salle in Canoas, Brazil and primary author on all of the reviews, confirms that the studies provide a strong case regarding the link between exercise and mental health. While further experiments are needed to specify the types and amounts of exercise, Dr. Schuch stated that “the main message” of the reviews “is that people need to be active to improve their mental health.”

SOURCES
https://www.theatlantic.com/health/archive/2014/03/for-depression-prescribing-exercise-before-medication/284587/
https://www.mayoclinic.org/diseases-conditions/depression/in-depth/depression-and-exercise/art-20046495
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC474733/

Obesity: The Public Health Epidemic Sweeping America

November 1, 2017

The prevalence of obesity in the United States has skyrocketed in the past few decades, leading to jarring statistics that indicate a rapidly increasing global public health epidemic. Data from the National Health and Nutrition Examination Survey states that more than 2 in 3 adults are considered overweight or obese; yet perhaps more disconcerting is the fact that approximately one-third of children and adolescents between the ages of 6 and 19 qualify as overweight or obese.

While the causes of obesity vary, factors include genetics, nutrition habits, lifestyle habits, geographic location, and socioeconomic status. The epigenetics of obesity demonstrate that genetic makeup plays an innate role, but can be mitigated and lessened by one’s activity choices and environment. As obesity is one of the primary risk factors for type 2 diabetes, heart disease, high blood pressure, and a host of other critically severe health problems, there is a pressing need for increased awareness and action steps surrounding the epidemic.

A recent study based at and conducted by UT Southwestern Medical Center reveals a strong genetic-environmental interaction: obesity significantly exacerbates the effects of gene variants that increase the risk of nonalcoholic fatty liver disease (NAFLD) by various metabolic pathways. If untreated and unmonitored, NAFLD can ultimately lead to cirrhosis—chronic liver disease—and liver cancer. Scientists found that the PNPLA3 gene variant spurred the strongest genetic-environmental interaction: “the first genetic cause of NAFLD ever identified.” One of the lead researchers in the study explains that people with lower BMI indexes are unlikely to have excess fat in the liver, despite having the PNPLA3 risk alleles. A longitudinal study further revealed that the risk of having cirrhosis among those with the risk allele increased 5.8 times, compared to those who were obese but lacked the risk allele.

The findings demonstrate an interaction between obesity and genetics, confirming the importance of both genetic screenings and early interventions. Nevertheless, DNA is not the sole culprit; while genetics inevitably account for some of a person’s obesity risk, genes can be countered and curbed by the implementation of healthy lifestyle interventions. Increasing data and studies indicate that sleep hygiene is a necessary element in terms of obesity prevention, coupled with consistent physical activity and exercise.

Thus, although there is no single approach to prevent or treat overweight and obesity, the importance of diet and exercise cannot be understated—particularly with younger children and adolescent, as childhood obesity almost inevitably leads to adulthood obesity. While some studies suggest that the epidemic will worsen and hit new highs, others advocate for the imminent urgency of different treatment approaches, including collaboration with the food and restaurant industries regarding calories and portion sizes. Regardless of societal and external factors, the epigenetics of obesity can be influenced by our behavior and actions: namely, positive and healthy lifestyle interventions.

To learn more about personalized approaches & strategies to address weight management and obesity, attend our pre-conference Obesity Management Workshop in Las Vegas on December 13th, 2017.