1655-P: Multiomics Analysis of Sarcopenic Obesity

Background: Sarcopenic obesity is a critical characteristic of type 2 diabetes. This study aimed to investigate its pathological basis using integrated omics and db/db/mice, a model representing this condition.

Methods: The study involved housing 8-week-old db/m and db/db/mice for 8 weeks. Various analyses were conducted, including gene expression in skeletal muscle and small intestine using next-generation sequencing, cytokine arrays of serum, assessment of metabolites in skeletal muscle, stool, and serum, and analysis of the gut microbiota. Histone modifications in small intestinal epithelial cells were profiled using CUT&Tag.

Results: db/db/mice exhibited significantly lower grip strength and higher visceral fat weight (p < 0.0001). Serum cytokine arrays demonstrated higher relative concentrations of VEGF-A (p < 0.0001) and lower concentrations of several other cytokines in db/db/mice. Moreover, mRNA sequencing revealed downregulation of Myh expression in skeletal muscle and upregulation of lipid and glucose transporters and downregulation of amino acid transporter in the small intestine of db/db/mice. The concentrations of saturated fatty acids in skeletal muscle were significantly higher, and the levels of essential amino acids were lower in db/db/mice. Gut microbiota analysis showed lower levels of Bacteroidetes and higher levels of Firmicutes in db/db/mice (p = 0.003). The integrated signal of histone modifications of lipid and glucose transporters was higher, while the integrated signal of histone modifications of amino acid transporter was lower in the db/db/mice.

Conclusion: The multi-omics approach provided insights into the epigenomic alterations in the small intestine, suggesting their involvement in the pathogenesis of sarcopenic obesity induced by overeating and inactivity.