Fitness
Exercise-activated PanK4 could aid in treating metabolic disorders
Physical activity is not only important for fitness but also for overall health. This is confirmed by a new study, which identified PanK4 as a key regulator of energy metabolism in skeletal muscle, regulating glucose uptake and fatty acid oxidation and being activated by physical exercise.
The study suggests that PanK4 could be a promising approach for treating metabolic disorders such as type 2 diabetes. The findings were published in the journal Nature Communications.
Skeletal muscle accounts for 30% to 40% of body weight and is critical for maintaining healthy glucose and lipid metabolism. Impairment in the skeletal muscle’s capacity to efficiently use or store glucose can disturb overall glucose homeostasis, potentially resulting in insulin resistance—a major risk factor for type 2 diabetes. Nevertheless, there are only a few therapeutic options that target musculature to treat metabolic disorders.
Studies in humans and mice
Physical activity enhances glucose uptake in muscles and promotes metabolic flexibility. Therefore, it is an effective method for improving glucose metabolism, particularly in insulin resistance and type 2 diabetes. However, the underlying molecular mechanisms are largely unknown.
These mechanisms were the focus of investigations by a broad international research team, including scientists from the German Center for Diabetes Research (DZD), coordinated by Prof. Dr. Maximilian Kleinert, head of the Department of Molecular Physiology of Exercise and Nutrition at the DIfE.
Using modern mass spectrometric methods, the team successfully identified proteins that are phosphorylated in human and animal muscles following physical exercise. One of these proteins is pantothenate kinase 4 (PanK4).
To elucidate the role of PanK4 in regulating energy metabolism in skeletal muscle, Kleinert and his team utilized various genetic mouse models (knockout and overexpression) to conduct comprehensive physiological investigations. These studies included treadmill running experiments and glucose tolerance tests to assess metabolic function.
Furthermore, the researchers analyzed human muscle tissue samples obtained post-exercise, conducted metabolic analyses, and utilized advanced molecular biological techniques such as RNA sequencing and protein analyses.
Mice lacking PanK4 are struggling
The researchers observed that the general absence of PanK4 in mice resulted in reduced growth and decreased skeletal muscle mass, among other effects. Furthermore, animals with a muscle-specific deficiency of PanK4 exhibited an increased fat content and impaired fatty acid oxidation within the muscle tissue.
Metabolomic analyses indicated that PanK4 plays a critical role in regulating acetyl-CoA levels in skeletal muscle. The absence of PanK4 led to a significant increase in acetyl-CoA, which disrupted the regulation of fatty acid oxidation and glucose metabolism. During training studies with mice specifically lacking PanK4 in their muscles, this was manifested by reduced glucose uptake during insulin stimulation and muscle contraction.
In contrast, mice with overexpression of PanK4 showed a significant improvement in glucose uptake in the muscles and a reduction in acetyl-CoA levels, underscoring the importance of PanK4 as a regulator of glucose metabolism. These results suggest that PanK4 plays a key role in maintaining metabolic flexibility, particularly in terms of the simultaneous utilization of fatty acids and glucose as energy sources.
Novel therapeutical approaches
Identifying PanK4 as a key regulator of muscle metabolism offers a promising new avenue for therapeutic interventions. According to Kleinert, “PanK4’s significance in metabolism places it alongside established key players like mTOR, AMPK, and Akt. Targeted modulation of PanK4 could potentially improve metabolic health and support blood sugar control, making it a promising target for therapies aimed at treating metabolic disorders such as type 2 diabetes.”
Furthermore, the finding that PanK4 is activated by physical activity and enhances energy metabolism in muscles underscores the importance of regular exercise for overall health. Kleinert emphasizes, “Regular physical activity not only enhances fitness but also has profound effects on metabolism, which can serve as a motivating factor for adopting an active lifestyle.”
Kleinert and his team plan to conduct further investigations to understand the precise mechanisms by which the phosphorylation of PanK4 by exercise or insulin modulates its activity. Specifically, they aim to elucidate how this phosphorylation event influences the regulation of acetyl-CoA levels and metabolic flexibility in skeletal muscle. Moreover, the role of PanK4 in other tissues, including the hypothalamus, and its impact on systemic energy homeostasis will be explored in greater detail.
More information:
Adriana Miranda-Cervantes et al, Pantothenate kinase 4 controls skeletal muscle substrate metabolism, Nature Communications (2025). DOI: 10.1038/s41467-024-55036-w
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Fitness
Bristol fitness expert offers free exercise for Parkinson’s
Anne said she first noticed something was wrong with her when she started to get cramps in her hands and she started to have difficulty walking without feeling stiff.
“I was sent for a brain scan and, as a result of that, they diagnosed Parkinson’s disease,” she said.
She said exercising and meeting others in the same position had helped her.
“I find exercising with other people helps as you don’t feel quite as isolated, you meet people with the same condition,” she said.
“I wouldn’t have done what I do now, or met the people I met now, if it wasn’t for the diagnosis.”
She said her son was “so enthusiastic” about everything he does.
“He certainly gets a lot of good remarks from people with Parkinson’s who feel they are dong something for themselves,” she said.
Fitness
Hybrid training: is this the secret to getting fitter and stronger?
Tough Mudder. CrossFit. Hyrox. Some of this century’s biggest fitness trends have one thing in common: they require feats of both strength and endurance. People used to pick a side: either you used weights and resistance machines to build your muscles or you did cardio for the sake of your heart and lungs. Now everyone wants to be a “hybrid athlete”. So is this the best way to get fit – and where do you start if you’re a complete beginner?
What exactly is hybrid training?
Matt Lee, a postdoctoral research fellow at the Deakin Institute for Physical Activity and Nutrition in Australia, says: “Hybrid training – also known as concurrent training – combines cardio and resistance exercises (eg weights) within the same programme, performed either within a single session, or across separate sessions during the week.”
Where does it come from?
Hybrid training is not a new concept – official physical activity guidelines have long recommended a combination of strength and cardio exercises. But among athletes it was believed that endurance training had a negative impact on strength development (known as the “interference effect”); recent research has shown that is not the case.
Phil Price, a senior lecturer in strength and conditioning science at St Mary’s University, Twickenham, is the author of The Science of Hybrid Training. He says the term itself was coined by Alex Viada in his influential 2015 book, The Hybrid Athlete (which was updated last year). “He was a powerlifter and then he started running, so he was actively chasing two goals that don’t necessarily support one another,” Price says. “Hybrid came to mean a very clear focus on two separate goals that come from two separate sports.”
Why it is so popular now?
The hybrid concept has evolved, making it appeal to anyone who wants to get fitter and stronger. “It has been used for anything that requires an endurance component and a strength component,” says Price. “The rise of CrossFit really developed it and it’s definitely been utilised by those who do Hyrox.” CrossFit is a high-intensity workout combining cardio with elements of weightlifting and gymnastics; Hyrox is a fitness competition mixing running with burpees, kettlebell carries, sled pushes and more.
Thomas Jones, an associate professor of sport, exercise and rehabilitation at Northumbria University, says: “Hyrox, which is super-popular at the moment, is almost the definition of hybrid. Those events are aerobic-based, so there’s a running element, and then there’s also a strength element and a power element.” Organisers say more than 1 million people entered a Hyrox race during the 2025/26 season, which culminates with the world championships in Stockholm this month.
A hybrid scene has also developed through social media, says Price. “More and more people have created these hybrid goals of, for example, doing a 500lb [227kg] squat and on the same day running a sub-five-minute mile. People are online competing with each other and through that, the culture has really boomed.”
What are the benefits?
Lee says hybrid training has numerous benefits for overall health and wellbeing, as well as sports performance. “Research has shown hybrid training can improve strength, muscle mass, power, endurance, speed and agility,” he says. “Beyond physical gains, studies of people who do hybrid training such as CrossFit report perceived improvements in quality of life, reduced stress, increased self-esteem and social benefits.” A previous study found this sense of belonging was significantly higher at CrossFit gyms than at traditional ones.
And hybrid training is a boon for busy schedules. “For many people, lack of time is a major barrier to exercise,” says Lee. “Combining cardio and resistance exercises within a single session is a time-efficient way to meet training goals.” I can relate to that – the “warrior” class at my local gym combines treadmill or rowing intervals with free-weight sets, for a full-body workout in just 45 minutes.
Alexios Batrakoulis, an assistant professor of applied and clinical exercise physiology at European University Cyprus, has conducted extensive research into hybrid training. He has seen great results from participants completing a 30-minute circuit-style hybrid programme up to three times a week. After 10 to 12 months, he reports: “Previously inactive middle-aged adults with overweight/obesity have significant body mass and fat reduction, as well as improvements in performance, cardiometabolic and psychological health.” He found that people enjoyed these “moderate to vigorous” circuits more than “traditional moderate-intensity continuous training”.
Is it suitable for beginners?
Absolutely – with the caveat that you check with your GP if you have any existing injuries or health conditions (and pay no attention to social media challenges). Kim Way, a senior lecturer at the Deakin Institute and an exercise physiologist with Exercise and Sports Science Australia, says beginners should do a combination of aerobic and resistance training two or three times a week.
“Start with low- to moderate-intensity exercise to help the body get used to the different exercises and get used to a routine. Use intervals to help break up aerobic activity to get used to moderate intensity with some recovery as well,” she says. “The talk test is a great way to gauge if you are going too hard with aerobic exercise. Moderate-intensity does make you a bit breathless, but you’d still be able to maintain a conversation with someone or be able to sing.” Build a foundation with four to six weeks of consistent training before adding another day or a high-intensity session, she adds.
What sort of aerobic exercise should I do?
This depends on your goals, says Lee. If you want to build up to a Hyrox event, running is essential – each race includes eight 1km runs – as is training on skiing and rowing machines. If you just want to get fitter, running is one option, but you may enjoy others more. “Substituting other cardio options such as swimming or cycling can still improve cardiovascular fitness while reducing the risk of overuse injuries that may occur from high volumes of running,” says Lee.
And what sort of strength training?
Again, if you’re training with Hyrox in mind, it make sense to focus on the strength-based events in the races: sled push and pull, farmer’s carry, sandbag lunges, wall balls … If you’re new to these exercises, says Way, scale back the weights, reps and sets. But if you just want to improve your general strength, she recommends “whole-body, compound movements such as squats, deadlifts and bench presses, which will provide immense benefit”.
“Two of the biggest predictors of quality of life in old age are strength (one-rep max) and aerobic fitness (VO2 max),” says Jones. “Strength is what often gets neglected by those who are new to exercise – they just run.”
Does the order I do them in matter?
“Research, including my own, suggests the order of cardio and resistance exercise has little influence on improving cardio fitness,” says Lee. “However, if a person’s goal is to improve strength, some research suggests completing resistance exercise before cardio might lead to greater strength gains, and that greater recovery time between modes (more than three hours) may benefit explosive strength development (power) – but more research is needed on these.”
Do I need to join a gym?
“For people with limited exercise experience, gyms can be a great place to start, as they provide access to professionals who can help develop suitable training plans and guidance on techniques,” says Lee. If you want to get into CrossFit, for example, there are about 10,000 gyms in 150 countries.
You can do your own hybrid training on the gym floor, using the cardio and resistance machines and/or free weights, but another option is joining a hybrid-style class. “Group classes can provide a sense of community and social support, which may also help with motivation and consistency,” says Lee. Some gyms offer dedicated Hyrox classes; others to look out for include bootcamp, circuits, functional fitness, and strength and conditioning. “When joining a group class, always remember to listen to your body,” says Way. “It is OK to stop and have a break if your body is not used to what is happening.”
Going to the gym doesn’t necessarily mean committing to a year-long membership. Apps such as ClassPass enable you to buy credits to use at a variety of gyms, and there are no-contract, pay-monthly budget chains such as PureGym and the Gym Group (which also offer classes). Community centres often have low-cost hybrid-style workouts – my local one has an hour’s circuit training for £8 – and many parks have free sessions, such as the beginners’ bootcamps and other classes run by Our Parks across the UK.
Can’t I do hybrid training at home?
Absolutely – you can combine cardio with home strength training. For example, you could follow the NHS’s Couch to 5K running programme alongside Our Parks’ Couch to Fitness programme. Jones says: “Remember what Joe Wicks was doing during Covid? That would be hybrid training.” Wicks is still posting free videos on YouTube – a recent 20-minute “strength, cardio and abs” workout fits the hybrid bill.
You don’t need any specialist equipment, at least initially. “For people just getting started, body weight exercises are enough,” says Jones. “If you can’t do 10 good push-ups, that’s a really good place to start.” Way suggests squats, lunges and pull-ups alongside your push-ups. When you’re ready to move on, “Filling up a backpack with cans or water bottles can add load,” she says.
Batrakoulis says you don’t need to invest in heavy weights to progress further, but some “functional training tools” can be useful: resistance bands, kettlebells, exercise balls and medicine balls; even suspension straps and battle ropes, if you have space.
Jones is also a fan of outdoor gyms in parks: “They’re great because it gives you the opportunity to run and then jump in and do some pull-ups and body-weight exercises.”
How much training should I do?
Lee says: “For overall health, the World Health Organization recommends adults aged 18 to 64 engage in at least 150-300 minutes a week of moderate-intensity aerobic physical activity, or 75-150 minutes a week of vigorous-intensity aerobic physical activity (or an equivalent combination of the two), plus muscle-strengthening activities at moderate or greater intensity on two days a week.” But don’t try to go from zero to hero, says Way: “If you are not currently meeting these guidelines, a slow and gradual buildup in activity is recommended.”
This is especially important in hybrid training, says Price, because of the various demands it puts on the body. “The endurance exercise is going to fatigue things in different ways to the resistance exercise. The high-intensity stuff is going to fatigue your body in different ways to the long-duration, low-intensity stuff. All of a sudden you’ve got a mix of everything.” His advice is to “start off slowly and progress very slowly because you don’t know how well your body will respond to the different stimuli and how close they are together”. The good news? “The body is really adaptable and will start to deal with that type of mixed stress quite well.”
Should I do cardio and strength training in the same session?
If you’re doing hybrid classes, clearly yes. Otherwise, says Jones, it’s down to preference and time. “I cycle some days and I lift weights other days. But some people wouldn’t like that approach. My wife, for instance, loves getting out in the garden and doing a circuit. So whatever works for you will be effective.”
Should I train every day?
No – rest days are essential. “It’s important to allow enough recovery time between sessions, not only for adaptations to occur, but to also minimise the risks of overuse injuries and overtraining,” says Lee. Way says beginners need at least 24-48 hours of recovery between sessions to help the body adjust.
Prioritise sleep. “Sleep for all exercise is really quite important. I think people underestimate that,” says Price. “I see it like a triad. Quite often if people are struggling with their training or they have a niggling recurring injury, they think there must be something that they’re doing wrong in training. But they need to go and make sure that they’re getting enough water, their nutrition’s right and they’re getting enough sleep. Quite a lot of the time, it’s their everyday life that isn’t providing that support to recover for them.”
Do I need to change my diet?
“As long as you’re getting good protein and carbs between sessions and lots of water, you should be good to go,” says Price. Specifically, he says, you need sufficient amounts of the amino acid leucine, which is found in most protein sources (meat, fish, cheese, beans, nuts, seeds, tofu etc). “Whenever the body tries to respond to the training stress from a strength point of view, the intake of protein is one of the signals to spark protein synthesis, which then improves muscle hypertrophy [growth]. So you’re trying to avoid that molecular process getting disrupted.”
Protein is often prioritised these days, but don’t overlook carbohydrates. “Carbohydrates broken down can get stored into muscle glycogen [fuel], and both strength and endurance training can reduce those stores. So if you’ve trained, you want to make sure that anything that was used from the previous session has been replenished,” says Price.
And finally … where do I sign up for the Hyrox world championships?
Sadly, that is invite-only for the top 0.5% of athletes. How about a Hyrox cruise instead?
Fitness
Tight on Space? You Can Still Get a Great Workout With This Compact Home Gym Equipment
Our team decided the TRX Home 2 System is the best multipurpose piece of compact home gym equipment you can invest in, thanks to its lightweight and multipurpose functions. I love that it supports both resistance training and cardio workouts while taking up zero surface area of my shoebox apartment.
All you do is hook the TRX Home 2 System onto the back of a door, beam, or pole with the included anchors. The hooks and suspension straps stay in place (which is essential for safety) while executing explosive movements like lunges and squats. In my apartment, I attached it to the back of my door and was able to install it properly on my first attempt. It’s never budged, no matter how much weight I put on it.
After using it a dozen times, I never lost balance or felt at risk of injury. It may look flimsy, but I attest it’s strong and mighty. For further stability, the straps feature grippy handles, which Sheridan recommends.
I know this product is top-notch because it has superior durability to withstand high-resistance, low-impact workouts. With weekly use, the anchors are not worn out and still feel good as new—you get what you pay for! Plus, the TRX Home 2 System was specifically designed by a Navy Seal over 20 years ago and has proven its effectiveness.
As a runner, it’s excellent for cross-training muscles I wouldn’t otherwise use, and stretching out my tired limbs. I plan on also using it on vacation for quick hotel room workouts because I need my daily endorphins.
Read More: Best Portable Home Gyms
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