Multi-organ multi-omic and gut microbiome markers of fat and sucrose dietary oversupply in cardiometabolic disease

Cardiometabolic disease is the greatest challenge facing global health. Increasingly, evidence suggests that Western diet comprising an over-supply of energy from fat and sucrose leads to obesity, insulin resistance, hypertension, and cardiovascular disease. Traditional preclinical animal studies of cardiometabolic disease often adopt a reductionist approach, focusing on individual components. To overcome this, we comprehensively assessed cardiometabolic phenotypes- anthropometric, physiological, and metabolic- along with the molecular changes consequent upon fat or sucrose dietary oversupply, or both in male C57BL/6J mice. Molecular assessment included measurement of the gut microbiome and several metabolite pools including plasma, heart, liver, and gut contents (cecal and fecal). In these mice, we identified key changes across phenotypes, metabolites, microbiota, and their interrelationship, and synthesized all the data into four distinct phenogroups that explain the variance across cardiometabolic parameters. These phenogroups provide insight into inter-organ regulation of Western diet-dependent cardiometabolic phenotypes, highlighting important avenues for further study.