Application of small animal CT and body composition analyzer in the study of mouse skeletal muscle atrophy

Study on the skeletal muscle atrophy in mice , the role of small animal body composition analyzer and CT

one. Experimental background

Skeletal muscle atrophy caused by aging and prolonged starvation is mainly controlled by fermented muscle fibers and generally has nothing to do with oxidized muscle fibers. However, the fiber type-specific mechanism of muscle fiber atrophy is currently unclear. In this study, the Fyn tyrosine kinase activates the mTORC1 signaling pathway, and the kinase also causes significant atrophy of the glycolysis fibers, but the kinase has little effect on oxidized muscle fibers. This is due to a decrease in Vps34 protein levels and a decrease in Vps34/p150/Beclin1/Atg14 complex inhibiting autophagy, a process that is independent of mTORC1 but dependent on STAT3. In the state of starvation, the activity of Fyn kinase in the glycolysis muscle fiber increases, but the activity of the enzyme in the oxidized muscle fiber does not increase. At the same time, the phosphorylation level of Y705-STAT3 increased with the decrease of Vps34 protein level. In Fyn-deficient muscle fibers, Vps34 protein levels and Y705-STAT3 phosphorylation levels cannot be regulated by starvation. These data suggest that the Fyn/STAT3/Vps34 pathway is responsible for the regulation of fiber type-specific autophagy and skeletal muscle atrophy.

two. Experimental Materials

Transgenic mice, animal body composition analyzer (EchoMRI, Houston), small animal full-quantity CT (Latheta LCT200, Hitachi-Aloka, Japan).

three. Partial experimental results

Figure 1. (D) Physiological characteristics of WT, HSA-FynB, and FynT transgenic mice (left) and micro-CT (Aloka Latheta LCT200) scans (right)

Figure 2. Characteristics of skeletal muscle atrophy in HSA-FynT and HSA-FynB transgenic mice

(A) Comparison of body weight between HSA-FynB (FynB) and HSA-FynT (FynT) mice and their respective control mice; (B) HSA-FynB (left) and HSA-FynT (right) transgenic mice and their respective controls The fat and muscle content of the mice in the group (measured by Echo MRI); (C) the muscle size of WT, HSA-FynB, and HSA-FynT transgenic mice; (D) WT, HSA-FynB, and HSA-FynT transgenic small Total tissue weight of the rat;

Micro-CT (Aloka Latheta LCT200) showed significant abnormalities in the skeletal structure of transgenic mice (Figure 1D). HSA-FynT transgenic mice have significant bulges in the posterior neck. The hip and hind leg tissues of HSA-FynB transgenic mice were significantly reduced, but no swelling of the posterior neck was observed. CT scans showed that the bulge on the back of the mouse was caused by spinal deformity (ie, posterior curvature of the spine) (Figure 1D). Consistent with these results, the weight loss of HSA-FynB transgenic mice of the same age was 15% lower than that of the control mice, while the body weight of HSA-FynT transgenic mice was about 1/3 of the weight of the control mice. (light 10g) (Figure 2A). Echo MRI results indicated that weight loss in FynT and FynB transgenic mice was due to a decrease in muscle mass (Figure 2B). There was no significant change in fat mass and water volume in HSA-FynB transgenic mice, but a small but significant increase in fat mass and a decrease in water volume in HSA-FynT transgenic mice. The reduction in muscle mass was accompanied by a decrease in skeletal muscle weight and no change in liver weight (Figures 2C and 2D). Surprisingly, the soleus muscle content was not significantly affected. The soleus muscle is mainly composed of oxidized muscle fibers (red), while other skeletal muscles are mainly composed of fermentative fibers (white, EDL) or composed of oxidized fibers and glycolysis fibers.

four. in conclusion

All studies have shown that the Fyn/STAT3/Vps34 pathway selectively regulates the atrophy of the fermented muscle fibers, a process that does not depend on the traditional mTORC1 pathway. The future will focus on the search and study of molecules upstream of this pathway.

From: Cell Reports 1, 557–569, May 31, 2012