Hepatic Fatty Acid Metabolism in Cardiomyopathic Hamster
A. Vecchini1, L. Binaglia1, M. Minieri2 and P. Di Nardo2.
1Istituto di Biochimica e Chimica Medica, Università di Perugia, Perugia; 2Dipartimento di Medicina Interna, Università di Roma "Tor Vergata", Roma, Italy.
The biochemical defect underlying the onset of cardiomyopathy in UM-X7.1 cardiomyopathic hamster (CMPH) is still unclear, although the recent evidence for a mutation in the d-sarcoglycan gene that maps to the disease locus could be reasonably considered to represent the primum movens of the cascade of events leading to cardiomyopathy. Meanwhile, convincing evidences demonstrating that dietary factors are involved in the development of the histopathological changes occurring during the early stages of the heart injury have been obtained. Indeed, CMPH feeding vegetal diets do not exhibit the morphological changes of the cardiac tissue preceding the early clinical signs of cardiomyopathy while their lifespan increases significantly, when compared to that of hamsters feeding a conventional diet. The observation that the insulin plasma level of CMPH is about one fourth of that measured in the plasma of Golden Syrian hamsters (GSH) raised the hypothesis that the enzymatic machinery of lipid metabolism is impaired in CMPH. Indeed, it is known that insulin regulates the transcription of several genes such as fatty acid synthase and stearoyl-CoA desaturase, such effect being reversed by dietary polyunsaturated fatty acids. Evidence was obtained that the activity of the aforementioned enzymes is differently modulated in CMPH and in GSH by dietary manipulations. Indeed, the hepatic utilization of intraperitoneally-injected [2-3H]glycerol and [1,2-14C]acetate in five month-old CMPH and GSH feeding standard pellet was significantly lower in CMPH than in controls, fatty acid synthase and D-9 desaturase activities being strongly depressed in CMPH. In addition, it was found that liver stearoyl-CoA desaturase-1, fatty acid synthase and protein S14 mRNA levels are lower in CMPH than in GSH feeding the same standard pellet. After  24h  feeding a vegetal diet, both fatty acid synthase and D-9 desaturase enzymatic activities and mRNA levels encoding the same enzymes were comparable in the two hamster strains whereas the fatty acid synthase and D-9 desaturase activities were, respectively, about 4-times and 2-times higher in GSH than in CMPH, when animals fed a high fructose diet. A possible relationhp between the functional impairment of heart in CMPH and the reduced response of the hepatic lipogenic enzymes to dietary factors is discussed.