Weightlifting may be more beneficial for blood sugar control than currently believed. (Photo by Unsplash+ in collaboration with Getty Images)

In A Nutshell

• Mice that lifted weights showed better blood sugar control than mice that ran on wheels, despite not building extra muscle or improving cardiovascular fitness.
• Weightlifting more effectively reduced dangerous visceral fat around organs, while running uniquely increased calorie-burning brown fat.
• The metabolic benefits happened through changes inside muscle cells rather than muscle growth, challenging assumptions about how resistance exercise works.
• These mouse findings suggest weightlifting deserves more attention for managing blood sugar, though human studies are needed to confirm the results translate to people.

Conventional wisdom says cardio is king for fighting obesity and diabetes. A study involving mice now suggests we should take a closer look at weightlifting. When researchers pitted resistance training against running in obese mice, the lifters came out ahead on three critical measures of blood sugar control.

Male mice fed a high-fat diet for eight weeks either lifted weights, ran on wheels, or remained sedentary. Both exercise groups gained less weight than their inactive counterparts. But weightlifting proved superior when scientists tested insulin sensitivity and glucose tolerance, key markers that predict diabetes risk.

The research, published in the Journal of Sport and Health Science adds to growing evidence that resistance training deserves more attention in conversations about metabolic health. Researchers at the University of Virginia and Virginia Tech published their results in the Journal of Sport and Health Science.

Teaching Mice to Squat

Scientists developed a novel weightlifting system for the study. Mice wore small collars and had to lift a weighted cage lid in a squat-like motion to reach their food. The weight started at 100% of each mouse’s body weight and increased by 20% daily until reaching 240% of body weight, where it remained for the study duration. Mice averaged 231 lifts per day.

Running mice had access to voluntary running wheels and covered about 10.5 kilometers daily. The voluntary nature of both exercise models matters because it mirrors how humans choose to exercise rather than being forced into activity.

Study author Zhen Yan said this weightlifting model addresses limitations of previous resistance exercise studies in mice that involved stressful approaches like forced ladder climbing.

Research conducted by Fralin Biomedical Research at Virginia Tech Professor Zhen Yan (left), Ryan Montalvo, and others compared the effects of endurance and resistance exercise in mice fed a high-fat diet. (Credit: Clayton Metz/Virginia Tech)

Three Wins for Weightlifting

After eight weeks, researchers measured several indicators of metabolic health. High-fat diet caused mice to develop elevated blood sugar and insulin levels, early warning signs associated with developing insulin resistance and type 2 diabetes.

On the first test, called HOMA-IR, weightlifting mice had lower scores than sedentary mice on high-fat diet, indicating improved insulin sensitivity. Running mice showed no significant improvement on this measure.

During glucose tolerance testing, researchers injected mice with sugar and measured how quickly blood glucose levels returned to normal. Weightlifting mice cleared glucose faster than sedentary mice, while running mice showed only partial improvement.

The third test involved injecting insulin and measuring the blood sugar response. Weightlifting again demonstrated more robust benefits than running for improving whole-body insulin sensitivity.

The Fat Loss Pattern

Both exercise types reduced fat accumulation compared to sedentary mice on high-fat diet. Weightlifting proved more effective at shrinking visceral fat (the dangerous fat around organs) and subcutaneous fat (fat under the skin). Running increased brown fat, a tissue type associated with calorie burning.

Body composition analysis revealed something surprising: neither exercise changed lean muscle mass when normalized to bone length. Weightlifting did not significantly increase muscle size despite daily resistance training. The metabolic improvements happened without measurable muscle growth, suggesting something changed inside muscle cells rather than their size.

Runners Still Won on Fitness

Running mice, as expected, performed better on treadmill tests than any other group. They ran longer distances before exhaustion. Running also increased the weight of hindlimb muscles and heart.

Neither exercise modality changed the contractile properties of muscles or cardiac function in young mice after eight weeks. The disconnect stands out: weightlifting mice couldn’t run any farther than sedentary mice, yet their blood sugar control surpassed runners.

What This Means for Exercise Recommendations

Exercise remains one of the most effective treatments for obesity and type 2 diabetes. Current American College of Sports Medicine guidelines recommend both endurance and resistance exercise for people with the condition, typically performed multiple times per week.

Most research has focused on endurance exercise like running, cycling, or swimming. Fewer studies have directly compared resistance and endurance training, particularly in animal models. The available human studies show mixed results, with some indicating resistance training improves long-term blood sugar markers more effectively than endurance training, particularly in people with normal-weight type 2 diabetes.

Why Weightlifting Might Work Better

Resistance exercise may enhance what researchers call “anabolic sensitivity,” meaning muscle tissue becomes more responsive to growth signals from insulin and other factors. Skeletal muscle accounts for most insulin-stimulated glucose uptake in the body, so improving muscle insulin sensitivity can have large effects on whole-body glucose metabolism.

Researchers examined protein signaling in skeletal muscle to understand the mechanisms. High-fat diet blunted insulin-stimulated activity of Akt, a key protein in the insulin signaling pathway. Exercise showed subtle trends toward improvement, though the effects did not reach statistical significance.

The study measured other markers related to protein synthesis, breakdown, and mitochondrial content. None showed definitive patterns that explained why weightlifting outperformed running for glucose control. The superior metabolic benefits appear to occur through mechanisms beyond simple muscle growth or obvious changes in insulin signaling proteins.

Cardio still provides key benefits like improved exercise capacity and brown fat activation. (Photo by Anton Pentegov on Shutterstock)

Study Limitations

The research used only male mice. Sex differences in exercise response have been documented, though their relevance to metabolic outcomes remains unclear. Female mice should be included in future research.

The eight-week duration may be too short to detect some outcomes. Longer studies could reveal additional differences in muscle mass, contractile function, or cardiac performance. Young mice were used, whereas human patients with type 2 diabetes are typically older.

Practical Takeaways

Simple resistance exercises can often be done at home with minimal equipment. In these mice, resistance training provided metabolic benefits that running did not. Whether this translates consistently to humans requires more research, as human studies show mixed results.

The findings don’t suggest abandoning cardio. Running provided unique benefits including improved exercise capacity and brown fat activation. Combining both exercise types can be very effective, as some human studies have shown.

In summation, the study indicates resistance training deserves equal consideration with cardio for blood sugar management. Weightlifting improved glucose and insulin tolerance in these mice beyond what running provided, despite not enhancing cardiovascular fitness or muscle size. For people struggling with blood sugar control, the weight rack might deserve equal billing with the treadmill, though human studies are needed to confirm these mouse findings translate to people.

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Disclaimer: This article discusses preclinical research conducted in mice. While these findings contribute to our understanding of exercise and metabolism, they have not been tested in humans. This information is for educational purposes and should not replace medical advice from your healthcare provider.

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Paper Summary

Methodology

Researchers divided male C57BL/6J mice (8-10 weeks old) into four groups: normal chow sedentary, high-fat diet sedentary, high-fat diet with voluntary wheel running (endurance exercise), and high-fat diet with weightlifting (resistance exercise). High-fat diet provided 60% of calories from fat. The weightlifting system required mice to lift a weighted cage lid in a squat-like motion to access food. Weight increased progressively from 100% to 240% of body weight over eight days, then remained constant. Running mice had continuous access to voluntary running wheels. All interventions lasted eight weeks. Researchers measured body weight weekly and performed endpoint assessments including body composition by EchoMRI, treadmill exercise testing, muscle contractile function, echocardiography, glucose and insulin tolerance tests, and skeletal muscle protein expression by Western blot.

Results

Both exercise interventions significantly reduced body weight gain compared to sedentary high-fat diet mice due to decreased fat mass without changes in lean mass. Weightlifting more effectively reduced visceral (epididymal) and subcutaneous (inguinal) fat accumulation, while running uniquely enlarged brown fat mass. Running improved exercise capacity on treadmill testing and increased skeletal muscle and heart weight. Neither exercise modality altered muscle contractile properties or cardiac function after eight weeks. Critically, weightlifting demonstrated superior benefits for improving insulin resistance (HOMA-IR), glucose tolerance, and insulin tolerance compared to running. High-fat diet diminished insulin-stimulated Akt phosphorylation in skeletal muscle across all groups, with subtle but not statistically significant improvements from exercise.

Limitations

The study examined only male mice, limiting generalizability to female subjects. The eight-week duration may be insufficient to detect long-term changes in muscle contractility, cardiac function, or sarcopenia. Young mice were used, whereas human patients with type 2 diabetes are typically older. The study did not identify definitive molecular mechanisms explaining the superior metabolic benefits of resistance versus endurance exercise. Insulin signaling markers showed high variability and subtle effects. Future research should include female mice, longer intervention durations, older animals, and additional mechanistic investigations including adipose tissue analysis and muscle-fat crosstalk.

Funding and Disclosures

The study was supported by National Institutes of Health grants NIH-R01AR050429 and NIH-R01AR077440, and a grant from Red Gates Foundation to author Zhen Yan. The authors declare no competing interests. All experiments were approved by the Institutional Animal Care and Use Committee at the University of Virginia (protocol #3762).

Publication Information

Shute RJ, Montalvo RN, Shen W, Guan Y, Yu Q, Zhang M, Yan Z. Weightlifting outperforms voluntary wheel running for improving adiposity and insulin sensitivity in obese mice. Journal of Sport and Health Science. 2025. DOI: 10.1016/j.jshs.2025.101100. Received June 12, 2025. Revised August 5, 2025. Accepted September 16, 2025.

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