Disrupted expression of genes essential for skeletal muscle fibre integrity and energy metabolism in Vitamin D deficient rats
Ramesh Gogulothu The Journal of Steroid Biochemistry and Molecular Biology Volume 197, March 2020, 105525
Highlights
• Vitamin D deficiency led to reduced expression of mTORC1 pathway proteins, contributing to decrease in muscle protein synthesis in skeletal muscle.
• Vitamin D insufficiency and deficiency led to a decrease in expression of myosin heavy chain and troponin isoforms which are essential for muscle contraction.
• Vitamin D insufficiency and deficiency reduced expression of myoglobin and mitochondria biogenesis factors ppargc1a & 1b.
• VDD decreased expression of glycolytic and oxidative enzymes, and Cs enzymatic activity, which indicate diminished oxidative capacity of skeletal muscle.
• Adequate amounts of Vitamin D are essential for optimal functioning of the skeletal muscle.
Vitamin D, a secosteroid that regulates mineral homeostasis via its actions in intestine, bone, kidneys and parathyroid glands, has many other target tissues, including skeletal muscle. In the present study, we used rats to examine if diet-induced vitamin D deficiency or insufficiency altered protein synthesis in muscle via the mTOR pathway, and impaired skeletal muscle quality by changing expression of genes needed for its function. Vitamin D deficiency resulted in reduced levels of phosphorylated mTOR, and suppressed mTOR-dependent phosphorylation of 4E-BP1 and p70-S6K, implying a decrease in activity of the protein synthesis machinery. These changes were coupled with up regulation of genes that are negative regulators of muscle growth (Fbxo32 & Trim63), leading to a net loss of skeletal muscle mass.
Vitamin D deficiency or insufficiency also led to a decrease in expression of both myosin and actin-associated proteins (Myh1, Myh2, Myh7, Tnnc1& Tnnt1), which are essential for generation of the mechanical force needed for muscle contraction. We also detected a decrease in expression of glycolytic and oxidative enzyme genes (Hk2, Pfkm, Cs, Pdk4 & βHad) and transcriptional coactivator genes (Ppargc-1α & Ppargc-1β) which indicate a low oxidative capacity of skeletal muscle in the vitamin D deficient state. Furthermore, decreased citrate synthase activity corroborates a decrease in mitochondrial density and aerobic capacity of the muscle.
In conclusion, our study demonstrates that chronic vitamin D deficiency or insufficiency reduced the size of skeletal muscle fibres, altered their composition, and decreased their oxidative potential. Most of the changes observed were reversible, either partially or completely, by restoring vitamin D to the diet of the deficient rats.
