TETRADECYLTHIOACETIC ACID REDUCES THE AMOUNT OF LIPID DROPLETS, INDUCES MEGAMITOCHONDRIA FORMATION AND INCREASES THE FATTY-ACID OXIDATION IN RAT-HEART

The effects of prolonged administration (3 months) of a 3-thia fatty a cid analogue and omega-3-fatty acids on cardiac fatty acid oxidation a nd the volume fraction of lipid droplets and mitochondria in cardiomyo cytes were investigated Doses were 1 g/day/kg body weight, except 150 mg/day/kg body weight for tetradecylthioacetic acid (a 3-thia fatty ac id). One group served as control and did not receive any treatment. Th e volume fraction of lipid droplets in cardiomyocytes was significantl y lower in the tetradecylthioacetic acid group compared to the other g roups. Mitochondrial beta-oxidation was 60% greater and fatty acyl-CoA oxidase activity was increased by 430% in the tetradecylthioacetic ac id group compared to control, This was accompanied by a greater volume fraction of mitochondria in cardiomyocytes (0.514 +/- 0.032% in tetra decylthioacetic acid v 0.318 +/- 0.007% in control) which was due to a n increased size of mitochondria. The volume fraction of mitochondria was also greater in eicosapentaenoic acid (EPA) treated rats compared to control, but the enzymic activities were unaffected. Docosahexaenoi c acid (DKA) treatment resulted in a greater volume fraction of lipid droplets in the cardiomgocytes, but the volume fraction of mitochondri a and enzymic activities were unaltered. These results indicate that E PA and DHA have different effects on the modulation of mitochondrial b iogenesis. Tetradecylthioacetic acid treatment results in megamitochon dria formation and increased peroxisomal and mitochondrial beta-oxidat ion with a concomitant reduction of lipid droplets in the cardiomyocyt es. (C) 1995 Academic Press Limited