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.

Provided by
Deutsches Institut für Ernährungsforschung Potsdam-Rehbrücke

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In the video, she shared 5 arm workouts she practises at the gym to tone them. She also gave a disclaimer with her post that one cannot instantly target fat loss in a specific area. They have to be consistent to see the results. Additionally, though these exercises helped her out, none of them are going to bring changes unless you make some healthy changes to your diet.

5 workouts to tone your arms

Carla shared the video with the caption, “I lost over 40kg. Here’s my arm workout routine to help tone my arms! I do this twice a week – one day focusing on the back and biceps and the other on the chest and triceps.” She further explained that she does 3 sets of each exercise with weights that are challenging enough for her to manage 10-12 repetitions of each workout. The 5 arm workouts are:

1. Assisted pull-up: An assisted pull-up is a bodyweight exercise that helps you work your way up to performing a full, unassisted pull-up. The strength training routine targets your chest, shoulders, arms, abdominal, and back muscles.

2. Barbell bent over rows: This strength-training routine targets the back, shoulders, rhomboids, scapular stabilisers, forearms and biceps, spinal erectors and, to some degree, your hamstring and glutes.

3. Hammer Curls: A relatively simple exercise for beginners, hammer curls target your biceps and other muscles in your arms.

4. Bicep Curls: Bicep curls are done with dumbbells. They mainly target the biceps brachii, brachialis and brachioradialis muscles.

5. Lat Pull-Down: The lat pull-down is an exercise you can do with a weight machine to work the muscles on the sides of your chest wall and upper back.

Carla begins the routine by doing warm-up exercises that include full-body stretches. The fitness influencer added that she does the same set of exercises for months until she ‘plateaus in some way’. She makes small adjustments when changing her routine.

Disclaimer: This article is for informational purposes only and not a substitute for professional medical advice. Always seek the advice of your doctor with any questions about a medical condition.

When most of us think about exercise, our minds usually conjure up images of running as fast as we can or sweating it out in a gym class.

But slower forms of movement – like walking and stretching – can be just as beneficial, especially when we’re overwhelmed.

High-intensity exercise benefits our overall health, but it causes a steep increase in cortisol levels – the hormones responsible for stress.

It’s undoubtedly good for us, and countless studies have proved that regular movement results in better sleep, lower blood pressure and improved mood, as well as helping to combat health conditions and diseases.

But, when you’re already going a million miles an hour, adding in an early morning gym class could be doing more harm than good. Low-intensity exercise, on the other hand, has the opposite effect. It reduces cortisol levels.

“If you are already fatigued and embark on a workout when your body’s energy reserves are low, exercise can further deplete your energy,” explains naturopath, nutritionist and founder of Edible Beauty, Anna Mitsios.

“Getting up early can be counterproductive as it can induce a stress response, especially if we haven’t had enough sleep to begin with. It can spark a rise in cortisol, which can increase blood sugar levels and, in turn, imbalance hormones.”

Keeping cortisol in check

When you’re exhausted and put your body under additional stress, you’re only adding to your likely already elevated cortisol levels.

Pushing through an intense exercise session can increase cortisol, negatively impacting your immune system, metabolism and mood. And instead of boosting your energy, it could have the reverse effect.

“Rather than getting the benefits of an endorphin rush, exercising while exhausted can further deplete reserves, leading to increased fatigue, which in the end makes you feel more tired,” explains Anna.

What’s more, increased stress and fatigue can impact our immune system, and adding more stress can leave you prone to illness and infection, which is the last thing we need when we’re already drained.

Slow it down – right down

Once upon a time, cortisol gave us a boost of energy to outrun an enemy or animal. Today, however, our cortisol spikes whenever someone cuts us off in traffic or we run late for an appointment. This triggers a stress response that constantly tells our brain that we’re in danger, even when that ‘danger’ is just the relentless pace of everyday life.

Slowing down and focusing on our breath through gentler exercise soothes our nervous system, which is exactly what we need when frazzled.

“You should walk away from exercise feeling good. You want to nourish your body rather than deplete it,” explains Ali Handley, founder of Sydney’s Bodylove Pilates.

She’s an advocate for Pilates, which has soared in popularity in recent years. Using a variety of props to challenge, strengthen and lengthen, it serves as a full-body workout, just at a more controlled pace.

“Women think they need to do a lot of cardio, but that’s just not the case. We often need a slower burn to support our bodies, activate our muscles and connect to our breathing. All those things help to make exercise an experience rather than a punishment.”

Rest is a right, not a reward

Lydia O’Donnell, a running coach and co-founder of the Femmi app, which provides training plans personalized to your menstrual cycle, echoes this sentiment.

“We’ve been fed this narrative of ‘no pain, no gain’, and it’s very masculine. It can be a slow jog around the block. It can be a walk. You can still move in a healthy, sustainable way that isn’t about trying to reach a marathon finishing line.”

If you love running, you don’t have to give it up. Instead, just aim to slow down the pace. Running slower can help build your aerobic base, which is good for covering longer distances without leaving you feeling zapped.

“No matter what exercise you do, you should enjoy moving and do what feels right for you,” says Lydia.

For many of us, walking is a great option to help lower cortisol levels. Not only can it increase cardiovascular fitness, lower blood pressure and help maintain a healthy weight without pushing your body beyond its limits, but you also receive mood-boosting endorphins, which can help counter feelings of overwhelm and exhaustion. Plus, it’s free and can be done practically anywhere.

“Walking is a form of stress relief,” says Anna. “It activates the parasympathetic nervous system, reducing the body’s stress response without the extra exertion of a gym session. If you need one or two cups of coffee to help you function at a 6am gym class, your body isn’t ready for the assault. You are better off sleeping in and calmly starting the day, waking with the sunlight and avoiding the harsh sound of the alarm.”

Permission to sleep in? Granted.