Combined administration of lauric acid and glucose improved cancer-derived cardiac atrophy in a mouse cachexia model

Cancer-derived myocardial damage is an important cause of death in cancer patients. However, the development of dietary interventions for treating such damage has not been advanced. Here, we investigated the effect of dietary intervention with lauric acid (LAA) and glucose, which was effective against skeletal muscle sarcopenia in a mouse cachexia model, on myocardial damage. Treatment of H9c2 rat cardiomyoblasts with lauric acid promoted mitochondrial respiration and increased ATP production by seahorse flux anlyasis, but did not increase oxidative stress. Glycolysis was also promoted by LAA. In contrast, mitochondrial respiration and ATP production were suppressed, and oxidative stress was increased in an in vitro cachexia model wherein cardiomyoblasts were treated with mouse cachexia ascites. Ascite-treated H9c2 cells with concurrent treatment with LAA and high glucose showed that mitochondrial respiration and glycolysis were promoted more than that in the control, and ATP was restored to the level in the control. Oxidative stress was also reduced by the combined treatment. In the mouse cachexia model, myocardiac atrophy and decreased levels of a marker of muscle maturity, SDS-soluble MYL1, were observed. When LAA in CE-2 diet was orally administered alone, no significant rescue was observed in the cancer-derived myocardial disorder. In contrast, combined oral administration of LAA and glucose recovered myocardial atrophy and MYL1 to levels observed in the control without increase in the cancer weight. Thus, it is suggested that dietary intervention using a combination of LAA and glucose for cancer cachexia might improve cancer-derived myocardial damage.

Keywords: atrophy; cachexia; mitochondria; myocardium; oxidative stress.