Adverse physiologic effects of Western diet on right ventricular structure and function: role of lipid accumulation and metabolic therapy

Abstract

Little is known about the impact of metabolic syndrome (MS) on right ventricular (RV) structure and function. We hypothesized that mice fed a Western diet (WD) would develop RV lipid accumulation and impaired RV function, which would be ameliorated with metformin. Male C57/Bl6 mice were fed a WD or standard rodent diet (SD) for eight weeks. A subset of mice underwent pulmonary artery banding (PAB). Treated mice were given 2.5 g/kg metformin mixed in food. Invasive hemodynamics, histology, Western, and quantitative polymerase chain reaction (qPCR) were performed using standard techniques. Lipid content was detected by Oil Red O staining. Mice fed a WD developed insulin resistance, RV hypertrophy, and higher RV systolic pressure compared with SD controls. Myocardial lipid accumulation was greater in the WD group and disproportionately affected the RV. These structural changes were associated with impaired RV diastolic function in WD mice. PAB-WD mice had greater RV hypertrophy, increased lipid deposition, and lower RV ejection fraction compared with PAB SD controls. Compared to untreated mice, metformin lowered HOMA-IR and prevented weight gain in mice fed a WD. Metformin reduced RV systolic pressure, prevented RV hypertrophy, and reduced RV lipid accumulation in both unstressed stressed conditions. RV diastolic function improved in WD mice treated with metformin. WD in mice leads to an elevation in pulmonary pressure, RV diastolic dysfunction, and disproportionate RV steatosis, which are exacerbated by PAB. Metformin prevents the deleterious effects of WD on RV function and myocardial steatosis in this model of the metabolic syndrome.