GENE-EXPRESSION OF MITOCHONDRIAL 3-HYDROXY-3-METHYLGLUTARYL-COA SYNTHASE IN A POORLY KETOGENIC MAMMAL - EFFECT OF STARVATION DURING THE NEONATAL-PERIOD OF THE PIGLET

The low ketogenic capacity of pigs correlates with a low activity of m itochondrial 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) synthase. To ide ntify the molecular mechanism controlling such activity, we isolated t he pig cDNA encoding this enzyme and analysed changes in mRNA levels a nd mitochondrial specific activity induced during development and star vation. Pig mitochondrial synthase showed a tissue-specific expression pattern. As with rat and human, the gene is expressed in liver and la rge intestine;however, the pig differs in that mRNA was not detected i n testis, kidney or small intestine. During development, pig mitochond rial HMG-CoA synthase gene expression showed interesting differences f rom that in the rat: (1) there was a 2-3 week lag in the postnatal ind uction; (2) the mRNA levels remained relatively abundant through the s uckling-weaning transition and at maturity, in contrast with the fall observed in rats at similar stages of development; and (3) the gene ex pression was highly induced by fasting during the suckling, whereas no such change in mitochondrial HMG-CoA synthase mRNA levels has been ob served in rat. The enzyme activity of mitochondrial HMG-CoA synthase i ncreased 27-fold during starvation in piglets, but remained one order of magnitude lower than rats. These results indicate that post-transcr iptional mechanism(s) and/or intrinsic differences in the encoded enzy me are responsible for the low activity of pig HMG-CoA synthase observ ed throughout development or after fasting.