Restoration of cardiac metabolic flexibility by acetate in high-fat diet-induced obesity is independent of ANP/BNP modulation.

The present study hypothesized that cardiac metabolic inflexibility is dependent on cardiac atrial natriuretic peptide/brain natriuretic peptide (ANP/BNP) alteration and histone deacetylase (HDAC) activity. We further sought to investigate the therapeutic potential of short-chain amino acid (SCFA) acetate in high-fat diet (HFD)-induced obese rat model. Adult male Wistar rats were assigned into groups ( = 6 per group): Control, Obese, and Sodium acetate (NaAc)-treated and Obese + NaAc-treated groups received distilled water once daily (oral gavage), 40% HFD ad libitum, 200 mg/kg NaAc once daily (oral gavage), and 40% HFD + NaAc, respectively. The treatments lasted for 12 weeks. HFD resulted in increased food intake, body weight, and cardiac mass. It also caused insulin resistance and enhanced β-cell function, increased fasting insulin, lactate, plasma and cardiac triglyceride, total cholesterol, lipid peroxidation, tumor necrosis factor-α, interleukin-6, HDAC, and cardiac troponin T and γ-glutamyl transferase, and decreased plasma and cardiac glutathione with unaltered cardiac ANP and BNP. However, these alterations were averted when treated with acetate. Taken together, these results indicate that obesity induces defective cardiac metabolic flexibility, which is accompanied by an elevated level of HDAC and not ANP/BNP alteration. The results also suggest that acetate ameliorates obesity-induced cardiac metabolic inflexibility by suppression of HDAC and independent of ANP/BNP modulation.