REGULATION OF GENE-EXPRESSION FOR LIPOGENIC ENZYMES IN THE LIVER AND ADIPOSE-TISSUE OF HEREDITARY HYPERTRIGLYCERIDEMIC, INSULIN-RESISTANT RATS - EFFECT OF DIETARY SUCROSE AND MARINE FISH-OIL

Hypertriglyceridemia is closely Linked to insulin resistance. Increase d dietary intake of n - 3 polyunsaturated fatty acids reverses both hy pertriglyceridemia and insulin resistance. To evaluate molecular mecha nisms responsible for the hypotriglyceridemic effects of n - 3 polyuns aturated fatty acids, the expression of genes for lipogenic enzymes in liver and white and brown adipose tissue was estimated in hereditary hypetriglyceridemic rats which underwent an euglycemic hyperinsulinemi c clamp; Before the clamp, animals were fed a basal or a high (63%) su crose diet with or without fish oil for two weeks. Results were compar ed to data obtained from control animals subjected to the identical pr otocol. In hereditary hypertriglyceridemic rats, gene expression for m alic enzyme was increased in liver and in brown adipose tissue but not in white adipose tissue. The high sucrose diet raised malic enzyme mR NA levels in liver of both hereditary hypertriglyceridemic and control rats, and this effect was more pronounced in brown adipose tissue. Su pplementing the high sucrose diet with fish oil led to a suppression o f malic enzyme gene expression in liver and brown adipose tissue of co ntrol rats. However. this inhibitory effect was not as pronounced in t he hereditary hypertriglyceridemic rats. Raised levels of fatty acid s ynthase mRNA in liver and brown adipose tissue of control rats fed hig h sucrose diet were suppressed by consumption of diet high in n - 3 fa tty acids. On the other hand, in hereditary hypertriglyceridemic rats Fed high sucrose diet, fish oil supplementation failed to suppress inc reased levels of fatty acid synthase mRNA in liver and in brown adipos e tissue. II appears that hereditary hypertriglyceridemic rats have el evated levels of mRNA for Lipogenic enzymes in liver and brown adipose tissue and dietary control leading to an alteration of hypertriglycer idemia influences gene expression of lipogenic enzymes only under spec ial dietary circumstances.