Integrative analysis of multiomics data identified acetylation as key variable of excessive energy metabolism in hyperthyroidism-induced osteoporosis rats

Abstract

Background: Results from the previous experiment have demonstrated bone loss and excess metabolism in Hyperthyroidism-induced rats. Thus, an underlying relationship between metabolism and bone loss was speculated. In addition, previous studies have shown the influence of acetylation on metabolism in tissues and diseases. The hypothesis from this case study suggests that excessive metabolism is induced by acetylation of vital metabolism enzymes. Results: In the case study, a HYP-induced osteoporosis rat model was used and the glucose metabolite was tested through the acetylation of proteins by the mass spectrometer. The results showed that pivotal enzymes of Glycolysis-Tricarboxylic acid cycle-Oxidative phosphorylation were acetylated along with upregulated metabolites. With all acetyly-lysine sites of related enzymes listed, the results in this study showed that bone loss in HYP rats was accompanied by the upregulation of CREB-binding protein (Crebbp, CBP). Furthermore, it is also indicated that CBP has a close relationship with the enhancement of LDHA which promotes glucose metabolism. Conclusions: Acetylation is highly correlated with excessive energy metabolism in HYP-induced osteoporotic rats, where a representation relationship between CBP and LDHA is demonstrated. Significance: Hyperthyroidism may lead to osteoporosis. Our study found an interesting phenomenon of hyperthyroidism induced-osteoporosis is that osteoporosis is accompanied by excessive glucose metabolism. In this process, some molecular mechanisms are still unclear. This study indicates a high degree of acetylation of metabolic enzymes, which may be closely related to excessive glucose metabolism. The relationship between CBP and LDHA was also investigated in this study, which showed that CBP and LDHA had some extent interaction. Glucose metabolism and acetylation maybe all associated with hyperthyroidism induced-osteoporosis. This data provides new insights into the molecular mechanisms of hyperthyroidism induced-osteoporosis.