The experimental mouse model of cardiovascular-kidney-metabolic syndrome reveals inflammatory changes in the heart and kidneys associated with CKM syndrome.

Cardiovascular-kidney-metabolic (CKM) syndrome, a recently proposed concept focusing on the interrelationship among cardiovascular system, chronic kidney disease, and metabolic risk factors, is associated with high morbidity and mortality. The mechanism of CKM syndrome has not yet been fully examined due to the lack of an animal model. We investigated whether an adenine-supplemented high-fat diet can induce CKM syndrome in mice. We fed normal chow diet (NCD), adenine-supplemented diet (AD), high-fat diet (HFD), and adenine-supplemented high-fat diet (AHFD) to 129/Sv mice for 16 weeks, and compared cardiac function, renal function, and histological characteristics. Also, RNA-sequencing was performed on the heart and kidney. Kidney fibrosis and dysfunction were the most severe in the AHFD group among four groups. Cardiac hypertrophy and fibrosis were observed in the AHFD group, but not in the other groups. Both kidney and cardiac RNA sequence analyses of AHFD group revealed the up-regulation of gene-sets involved in the inflammation and immune response. this suggest that the synergetic effect of AD and HFD on the development of mice CKM syndrome is in part explained by inflammation.