Study on the Mechanism of HLCS Gene Deficiency and Biotin Compensation Inhibiting Skeletal Muscle Development

Background Holocarboxylase synthetase (HLCS) facilitates the binding of biotin to biotin-dependent carboxylase enzymes (ACC, MCC, PC, and PCC) for carboxylation reactions. This research demonstrates a significant association between single nucleotide polymorphisms (SNPs) in the HLCS gene and the lean meat percentage (LEA) and growth characteristics of Duroc pigs. To deepen our understanding of HLCS functionality, we conducted validation experiments using skeletal muscle cell models. Results Interference with HLCS at the cellular level led to a significant increase in the expressions of ACC and PC, resulting in inhibited proliferation and myogenic differentiation of skeletal muscle cells. Biotin, a coenzyme of carboxylase commonly used to address HLCS deficiency, unexpectedly resulted in a notable decrease in HLCS gene expression and a significant inhibition of myogenic muscle differentiation in our experiment. To further investigate the impact of biotin on muscle development, varying concentrations of biotin were added to the mice's base diet. It was observed that the expression of the HLCS gene in muscle tissue decreased, consequently hindering muscle tissue development. Subsequent research revealed that following biotin supplementation, glycolysis and lipid catabolism in skeletal muscle cells and tissues were disrupted. Examination of the relevant signaling pathways indicated abnormal protein expression and phosphorylation in the MAPK and TGFβ signaling pathways upon the addition of biotin. Conclusions The HLCS gene plays a crucial role in skeletal muscle development in pigs, and biotin has been found to mitigate the hindrance resulting from HLCS deficiency. Conversely, under normal functioning of the HLCS gene, supplementation of biotin can impede muscle development.