Vitamin K2 regulates slow-twitch muscle fibers expression and mitochondrial function via SIRT1/SIRT3 signaling (Su X et al.)

Skeletal muscle is a critical player in preventing and treating obesity and insulin resistance (IR) since it triggers 80% of whole-body insulin-stimulated glucose uptake. Results of an animal study published recently in Nutrition support the idea that vitamin K2 upregulates SIRT1/SIRT3 signaling expression, leading to skeletal muscle fiber-type transformation from fast- to slow-twitch.

Research projects involving animals and humans have demonstrated reduced slow-twitch fibers, and mitochondrial dysfunction often accompanies obesity and IR. Earlier it has been found that vitamin K2 increases oxidative muscle fibers consisting of slow-twitch fibers and decreases glycolytic muscle fibers in obesity-induced mice. The present study’s authors revealed a potential mechanism in high-fat diet (HFD)-induced mice and palmitate acid (PA)-treated C2C12 cells, namely that vitamin K2 is beneficial in improving mitochondrial function via the SIRT1/SIRT3 signaling pathway can inhibit slow-twitch fiber decreases.

The researchers used in vitro and in vivo models for this study. Animals were on HFD for eight weeks. Different doses of vitamin K2 were supplemented by oral gavage, whereas C2C12 cells were exposed to varying amounts of PA for 16 h to mimic insulin resistance in vivo. Skeletal muscle types and mitochondrial function were evaluated, and C2C12 cells were transfected with SIRT1 siRNA. The researchers observed a reduction of oxidative fibers, insulin sensitivity, and mitochondrial function in HFD-fed mice and PA-treated C2C12 cells. Compared with controls, slow-twitch fibers were reduced to 80.2% in male HFD-fed mice. However, vitamin K2 administration significantly increased oxidative fibers and alleviated glycolytic fibers by improving ROS and mitochondrial respiratory via SIRT1 signaling.

The authors concluded that since vitamin K2 improved slow-twitch fibers both in vivo and in vitro, depending on the dose, their data may be of potential significance in the treatment of many muscular and neuromuscular diseases in humans.

“It has been shown before that obesity, diabetes, and aging influence muscle structure and quality. Obesity is associated with functional limitations in muscle performance and increased likelihood of developing a functional disability such as mobility, strength, postural and dynamic balance limitations,” says Dr. Katarzyna Maresz, president of the International Science and Health Foundation. “Therefore, by showing that vitamin K2 could be considered as a novel pharmacologic agent to improve slow-twitch fibers in health and disease, this research paper can be supportive for muscular disease therapies, doctors, and dieticians dealing with obesity and sarcopenic obesity, which is a new class of obesity in older adults, and also the sports segment,” she adds.


Su X, Zhou J, Wang W, Yin C, Wang F. VK2 regulates slow-twitch muscle fibers expression and mitochondrial function via SIRT1/SIRT3 signaling. Nutrition. 2022 Jan;93:111412. doi: 10.1016/j.nut.2021.111412.

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