Vitamin K2 Alleviates Insulin Resistance Associated Skeletal Muscle Atrophy via the AKT/mTOR Signalling Pathway
ABSTRACT Background Skeletal muscle atrophy and insulin resistance (IR) aggravate each other. Vitamin K2 (VK2) exhibits beneficial effects on IR, but whether it improves IR associated skeletal muscle atrophy remains insufficiently understood. This study aims to investigate the effects of VK2 on IR a...
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Wiley
2025-06-01
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| Series: | Journal of Cachexia, Sarcopenia and Muscle |
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| Online Access: | https://doi.org/10.1002/jcsm.13840 |
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| author | Yingfeng Zhang Yina Wang Zhu Ming Bin Li Haitao Qi Hongquan Xie Guoliang Wang Jiepeng Chen Lili Duan Ran Li Ying Li |
| author_facet | Yingfeng Zhang Yina Wang Zhu Ming Bin Li Haitao Qi Hongquan Xie Guoliang Wang Jiepeng Chen Lili Duan Ran Li Ying Li |
| author_sort | Yingfeng Zhang |
| collection | DOAJ |
| description | ABSTRACT Background Skeletal muscle atrophy and insulin resistance (IR) aggravate each other. Vitamin K2 (VK2) exhibits beneficial effects on IR, but whether it improves IR associated skeletal muscle atrophy remains insufficiently understood. This study aims to investigate the effects of VK2 on IR associated skeletal muscle atrophy in high‐fat diet (HFD) mice and type 2 diabetes mellitus (T2DM) patients and explore the potential mechanisms. Methods VK2 was administered to HFD‐fed C57BL/6 mice for 16 weeks. Grip strength, exercise capacity, oral glucose tolerance test (OGTT) and body fat rate were measured. Animals were sacrificed, and skeletal muscle and serum samples were collected to analyse muscle atrophy, glucose and lipid levels. The gene expression profile of skeletal muscle was determined by RNA sequencing. C2C12 cells were cultured for gene knockdown and overexpression experiments. For the randomized controlled trial (RCT), a total of 102 T2DM patients aged 50–80 years were recruited and randomly assigned to receive yogurt (one cup per day) with or without VK2 fortification (90 μg/day) for 6 months. Grip strength, skeletal muscle mass (SM), skeletal muscle mass index (SMI), 6‐m gait speed (6‐m GS), glycated haemoglobin (HbA1c), fasting blood glucose (FBG), fasting insulin (FINS) and homeostasis model assessment of insulin resistance (HOMA‐IR) were measured at 0, 3 and 6 months, respectively. Results VK2 significantly improved grip strength (p < 0.01) and exercise capacity (all p < 0.05) in HFD‐fed mice. At the tissue level, VK2 increased skeletal muscle mass (p < 0.05) and cross‐sectional area of muscle fibres (p < 0.05), while reducing the proportion of fast‐twitch fibres (p < 0.01). VK2 treatment decreased body fat rate (p < 0.01) accompanied by enhanced whole‐body energy metabolism. VK2 also diminished the glucolipid metabolism parameters, including glucose (p < 0.01), HOMA‐IR (p < 0.01) and serum lipid levels. Regarding the mechanism, VK2 promoted the phosphorylation of proteins in the FAK‐AKT–mTOR‐P70S6K pathway by targeting Ccn2, thereby enhancing protein synthesis of C2C12 myotubes. In the RCT study, VK2 supplementation significantly increased grip strength (ptreatment × time = 0.017), SM (ptreatment × time = 0.001), SMI (ptreatment × time < 0.001) and decreased HbA1c (ptreatment × time < 0.001), FBG (ptreatment × time = 0.056), FINS (ptreatment × time < 0.001), and HOMA‐IR (ptreatment × time < 0.001) in T2DM subjects. Conclusions Our findings demonstrated the beneficial effects of VK2 on insulin resistance related skeletal muscle atrophy by promoting protein synthesis via the AKT/mTOR pathway. |
| format | Article |
| id | doaj-art-64d4e47fbf4a4c68a395844380890a99 |
| institution | Kabale University |
| issn | 2190-5991 2190-6009 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Wiley |
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| series | Journal of Cachexia, Sarcopenia and Muscle |
| spelling | doaj-art-64d4e47fbf4a4c68a395844380890a992025-08-20T03:32:25ZengWileyJournal of Cachexia, Sarcopenia and Muscle2190-59912190-60092025-06-01163n/an/a10.1002/jcsm.13840Vitamin K2 Alleviates Insulin Resistance Associated Skeletal Muscle Atrophy via the AKT/mTOR Signalling PathwayYingfeng Zhang0Yina Wang1Zhu Ming2Bin Li3Haitao Qi4Hongquan Xie5Guoliang Wang6Jiepeng Chen7Lili Duan8Ran Li9Ying Li10Department of Nutrition and Food Hygiene School of Public Health, Harbin Medical University Harbin ChinaDepartment of Nutrition and Food Hygiene School of Public Health, Harbin Medical University Harbin ChinaDepartment of Nutrition and Food Hygiene School of Public Health, Harbin Medical University Harbin ChinaDepartment of Nutrition and Food Hygiene School of Public Health, Harbin Medical University Harbin ChinaDepartment of Nutrition and Food Hygiene School of Public Health, Harbin Medical University Harbin ChinaDepartment of Nutrition and Food Hygiene School of Public Health, Harbin Medical University Harbin ChinaDepartment of Nutrition and Food Hygiene School of Public Health, Harbin Medical University Harbin ChinaVitamin K2 Research Center Shenyang Pharmaceutical University Shenyang ChinaVitamin K2 Research Center Shenyang Pharmaceutical University Shenyang ChinaDepartment of Nutrition and Food Hygiene School of Public Health, Harbin Medical University Harbin ChinaDepartment of Nutrition and Food Hygiene School of Public Health, Harbin Medical University Harbin ChinaABSTRACT Background Skeletal muscle atrophy and insulin resistance (IR) aggravate each other. Vitamin K2 (VK2) exhibits beneficial effects on IR, but whether it improves IR associated skeletal muscle atrophy remains insufficiently understood. This study aims to investigate the effects of VK2 on IR associated skeletal muscle atrophy in high‐fat diet (HFD) mice and type 2 diabetes mellitus (T2DM) patients and explore the potential mechanisms. Methods VK2 was administered to HFD‐fed C57BL/6 mice for 16 weeks. Grip strength, exercise capacity, oral glucose tolerance test (OGTT) and body fat rate were measured. Animals were sacrificed, and skeletal muscle and serum samples were collected to analyse muscle atrophy, glucose and lipid levels. The gene expression profile of skeletal muscle was determined by RNA sequencing. C2C12 cells were cultured for gene knockdown and overexpression experiments. For the randomized controlled trial (RCT), a total of 102 T2DM patients aged 50–80 years were recruited and randomly assigned to receive yogurt (one cup per day) with or without VK2 fortification (90 μg/day) for 6 months. Grip strength, skeletal muscle mass (SM), skeletal muscle mass index (SMI), 6‐m gait speed (6‐m GS), glycated haemoglobin (HbA1c), fasting blood glucose (FBG), fasting insulin (FINS) and homeostasis model assessment of insulin resistance (HOMA‐IR) were measured at 0, 3 and 6 months, respectively. Results VK2 significantly improved grip strength (p < 0.01) and exercise capacity (all p < 0.05) in HFD‐fed mice. At the tissue level, VK2 increased skeletal muscle mass (p < 0.05) and cross‐sectional area of muscle fibres (p < 0.05), while reducing the proportion of fast‐twitch fibres (p < 0.01). VK2 treatment decreased body fat rate (p < 0.01) accompanied by enhanced whole‐body energy metabolism. VK2 also diminished the glucolipid metabolism parameters, including glucose (p < 0.01), HOMA‐IR (p < 0.01) and serum lipid levels. Regarding the mechanism, VK2 promoted the phosphorylation of proteins in the FAK‐AKT–mTOR‐P70S6K pathway by targeting Ccn2, thereby enhancing protein synthesis of C2C12 myotubes. In the RCT study, VK2 supplementation significantly increased grip strength (ptreatment × time = 0.017), SM (ptreatment × time = 0.001), SMI (ptreatment × time < 0.001) and decreased HbA1c (ptreatment × time < 0.001), FBG (ptreatment × time = 0.056), FINS (ptreatment × time < 0.001), and HOMA‐IR (ptreatment × time < 0.001) in T2DM subjects. Conclusions Our findings demonstrated the beneficial effects of VK2 on insulin resistance related skeletal muscle atrophy by promoting protein synthesis via the AKT/mTOR pathway.https://doi.org/10.1002/jcsm.13840AKT/mTOR pathwayinsulin resistancemenaquinone‐7skeletal muscle atrophyvitamin K2 |
| spellingShingle | Yingfeng Zhang Yina Wang Zhu Ming Bin Li Haitao Qi Hongquan Xie Guoliang Wang Jiepeng Chen Lili Duan Ran Li Ying Li Vitamin K2 Alleviates Insulin Resistance Associated Skeletal Muscle Atrophy via the AKT/mTOR Signalling Pathway Journal of Cachexia, Sarcopenia and Muscle AKT/mTOR pathway insulin resistance menaquinone‐7 skeletal muscle atrophy vitamin K2 |
| title | Vitamin K2 Alleviates Insulin Resistance Associated Skeletal Muscle Atrophy via the AKT/mTOR Signalling Pathway |
| title_full | Vitamin K2 Alleviates Insulin Resistance Associated Skeletal Muscle Atrophy via the AKT/mTOR Signalling Pathway |
| title_fullStr | Vitamin K2 Alleviates Insulin Resistance Associated Skeletal Muscle Atrophy via the AKT/mTOR Signalling Pathway |
| title_full_unstemmed | Vitamin K2 Alleviates Insulin Resistance Associated Skeletal Muscle Atrophy via the AKT/mTOR Signalling Pathway |
| title_short | Vitamin K2 Alleviates Insulin Resistance Associated Skeletal Muscle Atrophy via the AKT/mTOR Signalling Pathway |
| title_sort | vitamin k2 alleviates insulin resistance associated skeletal muscle atrophy via the akt mtor signalling pathway |
| topic | AKT/mTOR pathway insulin resistance menaquinone‐7 skeletal muscle atrophy vitamin K2 |
| url | https://doi.org/10.1002/jcsm.13840 |
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