These results suggest that the combination of three stressors in β2a-HFD-LN hearts produces severe cardiac hypertrophy and cell necrosis with increased profibrotic M2-macrophage populations, TGFβ-dependent cardiac fibroblast activation, and myocardial fibrosis, ultimately leading to a profibrotic HFpEF phenotype. The gene discussed is TGFB1; the disease is Myocardial fibrosis.