The effect of pharmacological memetic of exercise on high fat-induced cardiac myocytes injuries

Metabolic distress caused by an excess High-fat diet (HFD) is linked to various types of heart diseases. Inerestingly, recent studies have reported that HFD per se may directly damage 
cardiac cells independent of vascular diseases. Although mechanisms remain to be determined, dysregulation of autophagy (self-eating), metabolic signaling, and cellular senescence (aging) are possible factors involved in HFD-induced cardiac degeneration. Given that regular endurance exercise confers various cardioprotective benefits against metabolic diseases by promoting
autophagy, improving antioxidant capacity, and attenuating aging processes in the heart, we hypothesized that exercise-induced cardiac benefits would directly come from the cardiac cells
aside from the vascular origin. Our study, using a cell culture model of HDF, investigated whether a pharmacological exercise memetic 
(5-aminoimidazole-4-carboxamide-1-b-D-ribofuranoside:AICAR) rescued cardiac cells against HFD-induced cellular injuries via promoting autophagy, metabolic paradigm shifts, and anti-aging reprogramming. Rat ventricular cells were cultured in three different conditions: 1) normal culture media (CON, n=4), 2) high fat diet, treated with 0.5 mM sodium palmitate (Pal, n=4), and 3) high fat diet+ AICAR, treated with 0.5 mM sodium palmitate and 1 mM AICAR (Pal + AICAR). Our study showed that AICAR treatment mitigated mitochondrial morphological disfiguration but neither rescued HFD-induced autophagy disruption nor improved mitochondrial biogenesis nor enhanced glucose metabolic signaling compared to the HFD-treated group. Instead, AICAR rescued llpolysis and improved antioxidant capacity, which was downregulated by an HFD. Our data suggest that improved lipolysis in conjunction with antioxidant capacity by AICAR rather than autophagy modulation seems to provide cardiac protection against HFD-induced cell impairment as reflected in morphology data.
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Abstract/Description: Metabolic distress caused by an excess High-fat diet (HFD) is linked to various types of heart diseases. Inerestingly, recent studies have reported that HFD per se may directly damage cardiac cells independent of vascular diseases. Although mechanisms remain to be determined, dysregulation of autophagy (self-eating), metabolic signaling, and cellular senescence (aging) are possible factors involved in HFD-induced cardiac degeneration. Given that regular endurance exercise confers various cardioprotective benefits against metabolic diseases by promoting autophagy, improving antioxidant capacity, and attenuating aging processes in the heart, we hypothesized that exercise-induced cardiac benefits would directly come from the cardiac cells aside from the vascular origin. Our study, using a cell culture model of HDF, investigated whether a pharmacological exercise memetic (5-aminoimidazole-4-carboxamide-1-b-D-ribofuranoside:AICAR) rescued cardiac cells against HFD-induced cellular injuries via promoting autophagy, metabolic paradigm shifts, and anti-aging reprogramming. Rat ventricular cells were cultured in three different conditions: 1) normal culture media (CON, n=4), 2) high fat diet, treated with 0.5 mM sodium palmitate (Pal, n=4), and 3) high fat diet+ AICAR, treated with 0.5 mM sodium palmitate and 1 mM AICAR (Pal + AICAR). Our study showed that AICAR treatment mitigated mitochondrial morphological disfiguration but neither rescued HFD-induced autophagy disruption nor improved mitochondrial biogenesis nor enhanced glucose metabolic signaling compared to the HFD-treated group. Instead, AICAR rescued llpolysis and improved antioxidant capacity, which was downregulated by an HFD. Our data suggest that improved lipolysis in conjunction with antioxidant capacity by AICAR rather than autophagy modulation seems to provide cardiac protection against HFD-induced cell impairment as reflected in morphology data.
Subject(s): Undergraduate Research
pharmacological exercise memetic
HFD-induced cellular injuries