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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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Disha Patani, seen as a fitness icon, recalls an exercise accident saying “I couldn’t remember anything… I lost six months” after being left unconscious

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Disha Patani, seen as a fitness icon, recalls an exercise accident saying “I couldn’t remember anything… I lost six months” after being left unconscious
Disha Patani has revisited a dark chapter from her fitness journey, opening up about a gymnastics accident that left her with a serious head injury and a prolonged gap in memory. According to TOI, the actress described recounting how a training fall led to head trauma and memory loss severe enough to erase months of her life from recall.

According to TOI report, Patani says she was practising gymnastics on a hard terrace surface when she fell and struck her head, after which she “lost six months of my life because I couldn’t remember anything.” Patani shared that the fall caused trauma intense enough to erase the memory of an entire day. She said she regained consciousness only later, unable to recall how she ended up injured. The episode left her shaken but did little to temper her drive to train again. Patani said that structured practice and patience helped her retain confidence, although she needed months to regain rhythm and technique.

The actor has continued to remain a prominent public figure with regular appearances at events and industry gatherings, including her recent outings where she has been seen promoting her fitness centric image. In recent years, Disha Patani has remained consistently visible on the big screen.

She appeared alongside Tamil star Suriya in the large scale action drama Kanguva, which drew mixed responses from audiences. Her recent work also includes the action film Yodha and the thriller Ek Villain Returns. Looking ahead, Patani is set for a fresh pairing with Shahid Kapoor in the action thriller Arjun Ustara, now officially titled Romeo. The film has completed production and is scheduled for release on Valentine’s day 2025, according to media reports, marking her first collaboration with Kapoor.

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Don’t wait for Jan. 1: Why you need a fitness plan based on your actual health data – TownLift, Park City News

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Don’t wait for Jan. 1: Why you need a fitness plan based on your actual health data – TownLift, Park City News

PARK CITY, Utah — Every January, gyms across the country fill up with well-intentioned resolution-setters, only to empty out again by mid-February. The Smart Fit Method’s co-founder, Connor Darnbrough, has seen this cycle repeat year after year, and he’s determined to help people break it.

“The fitness industry relies heavily on January,” Darnbrough said. “They sell six-week programs and challenges because they know people are below their baseline after the holidays. But these quick fixes often lead to burnout, not sustainable results.”

A Different Approach to Fitness

What sets The Smart Fit Method apart is its commitment to personalization through data. Rather than prescribing the same program to everyone who walks through the door based solely on age, weight, or other generalizations, the studio uses comprehensive diagnostics to create truly individualized fitness plans.

Its signature offering is the Longevity Check, an hour-long health assessment that measures VO2 max (cardiovascular capacity), strength-to-weight ratio, grip strength, metabolic health, blood pressure, resting heart rate, body composition, and more. Typically priced at $400, these assessments are now available for $99 through December—a significant discount designed to help people start the new year with clarity about their actual health status.

“We’re using our clients’ actual diagnostics to dictate a program,” Darnbrough says. “This is very different than a typical gym where the trainer decides what you should do based on their preferences or training style.”

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Here’s how The Smart Fit Method is helping. Receive a complimentary first session and $200 in membership credit toward your first month. Redeem the first session before Dec. 15 until the end of January to start the membership. Start with your first free session on www.smartfitmethod.com and code BF2025 at booking, or email the studios parkcity@smartfitmethod.com for concierge booking.

The Science Behind Sustainable Results

The results speak for themselves. Members of The Smart Fit Method see an average 19% improvement in VO2 max within six months, along with a 70% increase in strength-to-weight ratio. These aren’t just impressive numbers—they translate to meaningful health outcomes.

According Darnbrough’s research on these metrics, a 19% VO2 max improvement can result in a 15-20% lower risk of mortality and effectively lower biological age by two to three years. The strength gains add another 20-40% reduction in mortality risk and three to five years of biological age improvement.

“When you combine those two things together, we’re looking at roughly 30-50% lower mortality risk for members using our program for over six months,” said Darnbrough. “It’s not just about how long you live, but your quality of life.”

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New Recovery Membership

Understanding that recovery is just as important as training, The Smart Fit Method is launching a new contrast therapy membership starting Dec. 1. For $149 per month, the first 25 members will have unlimited access to saunas and four cold plunge pools set at different temperatures.

This attention to detail in recovery mirrors their approach to fitness. Rather than offering a one-size-fits-all cold plunge at 37 degrees Fahrenheit, they maintain four different temperatures ranging from 35 to 55 degrees.

“Males and females have completely different cold tolerance,” Darnbrough said. “Most studies show males do best at 40-50 degrees Fahrenheit, while females typically benefit from 55-60 degrees. Setting a cold plunge too cold can actually do significant damage.”

The membership includes guided breathwork and meditation, along with complimentary electrolytes and tea. All sessions are booked through an app to ensure the facility isn’t overcrowded and members receive proper attention.

The Problem with New Year’s Programs

Darnbrough’s biggest pet peeve? Six-week transformation challenges that promise dramatic results.

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“These programs are designed to get people back over baseline quickly, but they usually overtrain them,” he says. “After six weeks, people are burnt out, their cortisol is high, and it’s extremely difficult to maintain those results.”

The issue, he explains, is that most programs don’t balance catabolic stress (exercise and training) with anabolic recovery (sleep, nutrition, and rest). People work out intensely, under-eat, and don’t get adequate recovery—a recipe for burnout.

“We look at exercise like medicine,” Darnbrough says. “Based on your symptoms, goals, and current health status, we determine the proper frequency, dosage, and intensity. That medicine is different for each person.”

Start Now, Not After the New Year

Rather than waiting until the new year to make changes, Darnbrough encourages people to start building sustainable habits now—or at minimum, to approach January 1st with a realistic plan.

“Bottle up your enthusiasm and use it over the course of the year,” he said. “Instead of drinking the entire bottle on Jan. 1 and burning out in two weeks, pace yourself.”

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Getting a Longevity Check before the new year provides a roadmap based on your actual health data—not generic recommendations. You’ll learn exactly how much cardiovascular training you need, how much strength work, and receive a complete nutritional plan with calorie, protein, fat, and carbohydrate targets based on your metabolism.

“Whether people do Smart Fit Method or not, they should definitely do the assessments,” Darnbrough said. “That will at least give them an idea of how to train based on their own biometrics and diagnostics.”

New holistic gym uses AI to work (out) smarter, not harder

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“This is the best full-body exercise if you can only do one thing a day”—an expert trainer on the most underrated move for improving strength and fitness

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“This is the best full-body exercise if you can only do one thing a day”—an expert trainer on the most underrated move for improving strength and fitness

If there’s one move that people roll their eyes at when they see it in a workout program, it’s the burpee. But as someone interested in functional, time-effective exercise, it’s one of my favourite moves.

Sara Haley is a trainer who focuses on workouts for midlife women and she agrees with me—burpees are underrated.

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