JCSM: Systemic vitamin D receptor ablation leads to disturbance of skeletal muscle glycogen storage in mice

Background: Vitamin D deficiency can lead to lesions in multiple organ systems, including skeletal muscle
.

Patients with severe vitamin D deficiency exhibit muscle weakness and are prone to frequent falls

Patients with severe vitamin D deficiency exhibit muscle weakness and are prone to frequent falls

Protein homeostasis is a major determinant of skeletal muscle mass

Results: The expression level of vdr-/- muscle-specific E3 ubiquitin ligase increased and protein ubiquitination increased, suggesting that protein degradation was up-regulated
.

The vdr-/- Foxo3 factor was not affected

Figure 1 vdr-/- mice exhibit higher rates of muscle protein degradation
.

(A, B) Serum growth hormone (A) and insulin-like growth factor 1 (B) levels were determined by ELISA

Figure 1 vdr-/- mice exhibit higher rates of muscle protein degradation

Figure 2 mTORC1 pathway and fasting protein synthesis in vdr-/- mice
.

(A - C) Western blot using anti-puromycin antibody to detect fasting protein synthesis in 3-week-old (A) and 7-week-old (B) and 7-week-old (C) hindlimb muscles of WT and vdr-/- Absorbed state protein synthesis

Figure 2 mTORC1 pathway and fasting protein synthesis in vdr-/- mice

Figure 3 vdr-/- skeletal muscle is not due to decreased mitochondrial activity
.

Representative western blot showing (A) TOMM20, UQCRC1, SDHA, COX4, (B) OXPHOS complex components, (C) MT-ND1, (D) OPA1, DRP1 and MFN2 protein levels

Figure 3 vdr-/- skeletal muscle is not due to decreased mitochondrial activity

Figure 4 Disorders of glycogen storage lead to atrophy of vdr-/- skeletal muscle in mice
.

In the absence of vdr-/- signaling, dysregulation of glycogen synthase and phosphorylase leads to increased skeletal muscle glycogen accumulation and leads to energy deprivation and defective glucose homeostasis
.
These defects lead to increased protein degradation and decreased protein synthesis, leading to skeletal muscle atrophy
.

Figure 4 Disorders of glycogen storage lead to atrophy of vdr-/- skeletal muscle in mice
.
In the absence of vdr-/- signaling, dysregulation of glycogen synthase and phosphorylase leads to increased skeletal muscle glycogen accumulation and leads to energy deprivation and defective glucose homeostasis
.
These defects lead to increased protein degradation and decreased protein synthesis, leading to skeletal muscle atrophy
.

CONCLUSION: Loss of vitamin D signaling leads to defective skeletal muscle glycogen storage, which in turn leads to muscle energy deficiency
.
The utilization of glycogen by vdr-/- skeletal muscle leads to a systemic defect in glucose homeostasis, which in turn leads to defective protein homeostasis and atrophy of skeletal muscle
.

Loss of vitamin D signaling leads to defective skeletal muscle glycogen storage, which in turn leads to muscle energy deficit
.
The utilization of glycogen by vdr-/- skeletal muscle leads to a systemic defect in glucose homeostasis, which in turn leads to defective protein homeostasis and atrophy of skeletal muscle
.

Original source:

Das A, Gopinath SD, Arimbasseri GA, Systemic ablation of vitamin D receptor leads to skeletal muscle glycogen storage disorder in mice .
J Cachexia Sarcopenia Muscle 2021 Dec 08

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