Acetate suppresses myocardial contraction via the short-chain fatty acid receptor GPR43

FIGURE 1. Acetate has no effect on cardiac output in rats. Representative original image of ultrasonic cardiogram in anesthetized rats by isoflurane (A). The maximal blood flow velocity at the left ventricular outflow tract (B), the velocity–time integral (C), the diameter of the left ventricular outflow tract (D), cardiac stroke volume (E), heart rate (F), and cardiac output (G) in anesthetized rats. N = 5. N: the number of rats. * p < 0.05.

FIGURE 2. Acetate inhibited the contractility of Langendorff-perfused rat hearts. Representative traces of left ventricular pressure in isolated heart perfusion with acetate (A). The maximal left ventricular developed pressure (B), left ventricular end-diastolic pressure (C), left ventricular developed pressure (D), the maximal differentials of LVDP (E,F), and heart rate (G) in Langendorff-perfused heart. N = 6. N: the number of rats. * p < 0.05, ** p < 0.01, *** p < 0.001.

FIGURE 3. Acetate inhibited contractility in isolated myocardial cells. Representative traces of myocardial contraction (A). The sarcomere contraction amplitude (B), diastolic sarcomere length (C), maximum contraction velocity (D), and maximum relaxation velocity (E) in isolated myocardial cells. N = 5, n = 10. N: the number of rats, n: the number of cells. * p < 0.05, ** p < 0.01, *** p < 0.001.

FIGURE 4. Acetate decreased the amplitude of calcium transient in rat cardiomyocytes. Original plot of calcium transient in isolated myocardial cell (A). The calcium transient amplitude (B) and calcium recovery rate (C), N = 5, n = 7. The Ca2+ content of sarcoplasmic reticulum in cardiomyocytes (D), N = 5 for each group, n = 5 for control group, n = 8 for acetate group. N: the number of rats, n: the number of cells. * p < 0.05.

FIGURE 5. Acetate had no effect on the activity of L-type calcium current and action potential in rat ventricular myocytes. Recording of L-type calcium current from isolated cardiomyocytes (A). Current density-voltage curve for L-type calcium current in cardiomyocytes with or without acetate (B), N = 5, n = 16. The max current density for L-type calcium current in cardiomyocytes (C), N = 5, n = 16. Representative action potential recordings in rat ventricular myocyte before and after perfusion with acetate (D). 90% of the duration of action potential in cardiomyocytes (E), N = 5, n = 9. N: the number of rats, n: the number of cells.

FIGURE 6. GLPG0974 prevented the acetate-induced inhibition of myocardial contraction. Photomicrographs showing GPR43 and RyR2 were co-expressed in myocardial cell (A), GPR43 was labeled red, RyR2 was labeled red green and DAPI was labeled blue in the nucleus; scale bar, 20 μm. The GPR43 protein expression in myocardial cells was observed by Western blot (B). Representative traces of myocardial contraction in isolated myocardial cells (C). The sarcomere contraction amplitude (D), diastolic sarcomere length (E), maximum contraction velocity (F), and maximum relaxation velocity (G) in the isolated myocardial cell. N = 5, n = 11. N: the number of rats, n: the number of cells. * p < 0.05, ** p < 0.01, *** p < 0.001.