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Exercise-activated PanK4 could aid in treating metabolic disorders

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Exercise-activated PanK4 could aid in treating metabolic disorders
Skeletal Muscle PanK4 regulates fatty acid oxidation. Credit: Nature Communications (2025). DOI: 10.1038/s41467-024-55036-w

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.

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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.

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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.

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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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Deutsches Institut für Ernährungsforschung Potsdam-Rehbrücke

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Exercise-activated PanK4 could aid in treating metabolic disorders (2025, January 21)
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Jogging 101: Benefits for Your Body and Mind

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Jogging 101: Benefits for Your Body and Mind

Walking and running share a number of benefits — but what about that sweet middle ground between the two?

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“Jogging is about creating a steady pace,” says sports and exercise medicine specialist Leonardo Oliveira, MD. “Instead of focusing on speed, you’re focused more on endurance with good, quality steps.”

Before your next jaunt, Dr. Oliveira shares the many benefits of jogging and how it can help improve your overall health and wellness.

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9 benefits of jogging

Unlike running, where you’re focused on targeting different heart rate zones, jogging involves keeping a more stable and persistent pace. If you’re jogging at a moderate intensity, for example, your target heart rate will usually fall into zone 2, at 60% to 70% of your max heart rate.

“When you’re jogging, you should be able to carry on a conversation as you breathe through your nose,” says Dr. Oliveira. “If you’re doing just 15 minutes of jogging three times a week, you’re already going to notice the benefits.”

Here’s how you can benefit from jogging.

1. Reduces stress

Jogging, like other exercises, can help decrease your stress levels. As an aerobic exercise, it helps release endorphins, which can boost your mood and create feelings of euphoria or satisfaction. Not only does it provide an outlet for pent-up energy, but jogging outside also allows you to spend more time in nature, which provides even more mental health benefits.

“Research shows exercise can be as effective as medication when treating depression because of its wide-ranging benefits,” says Dr. Oliveira.

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2. Burns calories

Jogging is a full-body exercise that offers a higher calorie burn than some other aerobic exercises. According to the widely used Compendium of Physical Activities, jogging burns about 7.5 calories per kilogram of body weight each hour. That means you can burn about:

  • 8 times as many calories as sitting quietly
  • 4 times as many calories as walking
  • 2.6 times as many calories as stationary cycling

“Jogging will burn more calories in a shorter period of time than cycling, especially if you’re not used to exercising,” reports Dr. Oliveira.

3. Improves insulin resistance and boosts metabolism

Insulin resistance is one of the biggest barriers to having a healthy metabolism. Insulin helps your body break down glucose for energy. But if your body can’t do that, your metabolism slows down, leading to:

  • Lower energy levels
  • Weight gain
  • An inability to burn fat

“Exercising at higher intensities helps increase metabolism and insulin resistance,” says Dr. Oliveira. “But researchers have also found that even lower-intensity exercises, like jogging, for longer periods of time can have the same effect.”

4. Strengthens your heart

Jogging also has positive impacts on your heart and its ability to pump blood to the rest of your body. That’s because it contributes to hypertrophy, or the strengthening of your heart’s muscle tissues.

“As you develop endurance, the amount of blood in one pump increases,” explains Dr. Oliveira. “When your heart gets stronger, it contracts more efficiently, which decreases your resting heart rate.”

5. Improves lung expansion and gas exchange

The more you work on building endurance and stamina, the more likely it is that you’ll improve your overall ability to breathe — both at rest and while jogging.

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“Consistent aerobic exercise helps your lungs get stronger and more efficient,” says Dr. Oliveira. “Over time, you won’t need to breathe as often because each breath brings in more oxygen than before.”

6. Activates muscles

Jogging activates major muscle groups, including your:

  • Quads
  • Hamstrings
  • Glutes
  • Core
  • Back

“Strength training is a good complement to jogging because it can help strengthen all the areas of your body,” says Dr. Oliveira. “This can help you handle longer distances.”

7. Reduces stiffness

“Jogging is one of those activities where once you get going, you start to feel better,” notes Dr. Oliveira. “It’s an exercise that helps warm up your muscles and lubricate your joints, which can help with the overall sense of stiffness that comes with age.”

That said, jogging is still a high-impact exercise because it forces you to bear down weight as your feet hit the pavement. Consider working with a physical therapist or athletic trainer to reduce the risk of further injury if you:

  • Have arthritis
  • Have an active injury
  • Had previous sprains or fractures in your lower body

8. Improves endurance

“The more you jog, the more you’ll increase your functional aerobic capacity,” says Dr. Oliveira. “Someone who jogs regularly will have better physical fitness that will help them last longer on a bike or a walk than someone who’s just getting started.”

Your ability to breathe and move also extends to other daily activities that demand cardiovascular strength and endurance, like climbing stairs.

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9. Provides better quality of life and other mental health benefits

Research shows that any amount of jogging — even just once a week — can improve your quality of life and lower your risk of dying from cancer and cardiovascular-related issues.

“Jogging is a great form of exercise, but it’s not the only one,” notes Dr. Oliveira. “The most important thing is to work on being healthy and strong. And for a lot of people, if you’re looking to advance your physical fitness, jogging is a good place to start.”

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Michelle Yeoh, 63, uses ‘exercise snacking’ to stay fit – here’s why mini workouts have big benefits

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Michelle Yeoh, 63, uses ‘exercise snacking’ to stay fit – here’s why mini workouts have big benefits

As an increasing number of scientific studies are published citing the benefits of ‘exercise snacking’ – short bouts of physical activity sprinkled throughout the day – one celeb has sworn by the practise for several years already. The woman in question? Acting great Michelle Yeoh. Below, we look at the power of mini workouts and why the Oscar-winner’s go-to move is so effective.

Stretching

Michelle revealed to Vogue that she incorporates fitness into her morning routine in a way that’s incredibly time-efficient. ‘Remember, you can do your kicks, you can do your stretches, while you are also waking up,’ she said. Indeed, research has shown that regular stretching can improve flexibility, reduce muscle stiffness and improve blood circulation – all crucial elements of healthy ageing.

And you don’t have to stretch for very long, either. One study found that while static stretching improves flexibility in adults, there was no additional benefit observed beyond four minutes per session or 10 minutes per week. So, it seems that a short stretching sesh (you don’t even have to get out of bed to do it) like Michelle’s is a very worthwhile habit to adopt.

Squats

In her Vogue interview, Michelle also shared that she performs squats most days while doing her skincare routine. Virtually every expert and trainer we speak to here at Women’s Health lists squats as one of the most important moves for women to do as they age. A compound exercise (when multiple muscle groups are used), squats also mirror the vital movement pattern of sitting down and getting back up again.

Numerous studies have highlighted the benefits of this simple exercise for posture, strength and power, and one paper even found that intermittent squat exercises performed during prolonged periods of sitting may boost brain power. Whether you’re squatting mid-moisturise like Michelle or while you’re waiting for the kettle to boil, the science suggests sprinkling squats into your day can be really quite powerful.

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The power of habit stacking

As Michelle’s routine shows, adopting a sustainable exercise routine often relies on habit stacking – adding a movement to something you already do every day, like doing your skincare or brushing your teeth.

BRB, we’re just off to do our daily squats.


After years living with endometriosis and undergoing seven rounds of IVF, Radio 4 presenter Emma Barnett turned to training with PT Frankie Holah to rebuild strength and a more positive relationship with her body. Download the Women’s Health UK app to access Frankie’s full training plan.

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Hannah Bradfield is a Senior Health and Fitness Writer for Women’s Health UK. An NCTJ-accredited journalist, Hannah graduated from Loughborough University with a BA in English and Sport Science and an MA in Media and Cultural Analysis.  She has been covering sports, health and fitness for the last five years and has created content for outlets including BBC Sport, BBC Sounds, Runner’s World and Stylist. She especially enjoys interviewing those working within the community to improve access to sport, exercise and wellness. Hannah is a 2024 John Schofield Trust Fellow and was also named a 2022 Rising Star in Journalism by The Printing Charity.  A keen runner, Hannah was firmly a sprinter growing up (also dabbling in long jump) but has since transitioned to longer-distance running. While 10K is her favoured race distance, she loves running or volunteering at parkrun every Saturday, followed, of course, by pastries. She’s always looking for fun new runs and races to do and brunch spots to try.

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I Have a Master’s in Exercise Science. These Are the Only 6 Strength Moves You Need To Build Muscle

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I Have a Master’s in Exercise Science. These Are the Only 6 Strength Moves You Need To Build Muscle

Strength training doesn’t have to be complicated. Fitness content on social media may leave you thinking that you should only work out at specific times, use certain weights and incorporate an ever-rotating assortment of moves — but to reap the full benefits of building muscle, you can actually keep things surprisingly simple.

The Physical Activity Guidelines for Americans recommends at least two days of resistance training, aka strength training, for adults each week as part of their workout routines. And those two days need only include six moves, Adrian Chavez, Ph.D., nutrition and health coach, tells TODAY.com.

It’s often the most advanced fitness routines that generate the most buzz online. And while having lots of different strength moves in your arsenal can stave off boredom at the gym, it’s not usually necessary, Chavez explains. Sticking to the basics and staying consistent will give you the most bang for your buck, he adds.

The Most Efficient Strength-Training Moves

The six moves Chavez says are most efficient for improving health and body composition are:

“Those movements cover all of the (major) muscle groups of the body,” Chavez says. “I wouldn’t necessarily say these are the only six movements that you need, but those are the ones that are going to work the largest amount of muscle in each movement.”

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Building muscle through strength training can boost longevity, a mood, bone density and more.

It’s also a key factor to improving metabolic health, Chavez points out. Muscle burns calories, even while you’re at rest. So, the more muscle you have, the more calories you’ll burn.

If you’re after efficient results, focusing on these six movements that target the body’s largest muscle groups will get you there since these muscles require the most energy to function.

Which Muscles Does Each Move Target?

The overhead press primarily targets the shoulders, says Chavez. It also works the triceps, the trapezius muscles in your upper back and the core.

Perform a chest press when you’re looking to strengthen your pectoralis muscles, the two largest in the chest. These muscles are responsible for lifting, rotating and pushing.

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By including a back row in your strength training routine, you’ll be working your upper back and biceps, says Chavez.

The overhead pull-down or pull-up will strengthen your latissimus dorsi muscles (lats), which extend from the lower back to the armpit. Chavez says you’ll be engaging your biceps, too.

Squats work the quadricep muscles (quads) in the thighs, hamstrings and glutes, says Chavez. They’ll also engage your core, since squats require stability.

Include deadlifts in your routine to challenge your quad muscles in the thigh, hamstrings, glutes and lower back, says Chavez. You can choose between the regular deadlift and the Romanian deadlift, or incorporate both into your workout.

Benefits of a Consistent Strength Training Routine

Studies show that consistency when strength training, rather than the complexity of your workout plan, is what makes the biggest difference for health. Any kind of resistance training compared to none at all improve sstrength, muscle function and endurance regardless of intensity, equipment type and variation, research shows.

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These six moves are not the only effective workouts for improving strength and altering body composition, but if you were to stick only to these six, you’d be in great shape, he explains.

Regular strength training will not only improve your physique but also your quality of life. “When you do a deadlift, that’s like picking up your kid,” Chavez says, comparing pull-ups to playing with them on the monkey bars.

“Carrying groceries, moving furniture, all of those things become a lot easier when you build some strength. And … these six movements cover all of the major muscle groups, so that will translate into really changing the way that you experience life,” he adds.

How to Add Variation

Once you’ve committed to a training plan you’ll use again and again, you may also want to mix things up, Chavez says.

To avoid boredom or to add an additional challenge, most of the six moves have variations.

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For example, narrow-stance squats isolate the quads. Or you can change the grip during bicep curls to also target the forearms. “Learning slight variations to these primary movements is how you really build out a good routine,” he says.

An ideal workout program includes strength training at least two times a week and additional sessions with a type of cardio you enjoy. Chavez plays basketball, runs and rides his bike in between strength training sessions. He also suggests walking, swimming or rowing.

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