Mitochondria are present in almost all cells of the body and as such, mitochondrial dysfunction often leads to multisystem disorders, with cardiomyopathies being one of the most prominent manifestations. Due to the genetic complexity and multi-systemic nature of mitochondrial dysfunction, one of the biggest limitations in the field is the lack of suitable research models that recapitulate human disease, particularly those driven by polygenic underpinnings. To this end, our lab recently analysed 107 strains of mice from the HMDP, a panel of genetically diverse inbred mouse strains, and identified four strains which demonstrate robust reductions in mitochondrial complex I abundance. We subsequently bred 2 of these strains (BXD44 and BXD71) and aged cohorts (n=10-16) and controls (C57Bl/6J) to 14 months. Anthropometric phenotyping across this study found that these mice display significantly increased weight gain from 16 weeks of age which is directly related to an increase in fat mass. This obesity phenotype is attributable to reduced activity and energy expenditure and results in glucose intolerance and insulin resistance. Furthermore, molecular analysis performed on the hearts of these mice demonstrated characteristic features of cardiomyopathy including reduced SERCA2 expression, and increase Myh7, while no change in fibrosis markers (colfa3/col1a1) was evident. These results indicate the presence of a cardiometabolic disease phenotype driven by mitochondrial dysfunction. These findings associated with global polygenic complex I insufficiency in these mice, highlight these strains as a useful new model to study cardiometabolic disease in a model organism.