Effects of high sucrose diet on hepatic enzymes: Function and expression

The physiological effects of dietary sucrose include hyperglycemia, and hepatic and peripheral insulin resistance. In this study Fisher 344 male weanling rats were fed a diet of either 65% sucrose (HSD) or standard lab chow (0% sucrose) for 90 days. We examined the effects of chronic HSD on hepatic enzymes, their quantity, function and activity.; Growth and liver weight to body weight ratios, were significantly decreased in rats fed HSD compared to those fed 0% sucrose diet. Total hepatic microsomal cytochrome P450 (CYP450) content was unaltered by HSD. Cytochrome P450 1A1 and 3A2 isoforms were significantly decreased in quantity in the sucrose fed rats while CYP1A2, 2B1,2 isoforms were not. The percentage of the total P450 accounted for by CYP1A1,2, 2B1,2 and 3A2 was significantly decreased in rats maintained on the HSD.; The activities of CYP1A1, 1A2 and 2B1,2 as determined by O-dealkylation of alkoxyresorufins were significantly decreased in the liver microsomes of HSD animals compared to those on standard lab chow. These decreases in activity of hepatic cytochromes suggest that HSD may also decrease the metabolism of xenobiotics that are substrates for these CYP450 isoforms. The activity of CYP3A2, was not significantly decreased in rats fed a HSD.; CYP1A2 is implicated in the microsomal-dependent mutagenesis of heterocyclic amines (HCAs). Aflatoxin B₁ (AFB₁) is a fungal toxin and food contaminant, and is implicated in human liver carcinogenesis. It is activated by CYP450 3A2, 1A2, and 2B1,2 isoforms. When liver microsomes were incubated with either of two HCAs (2-amino-3,8-dimethyl-imidazo[4,5- f]quinoxaline (MeIQx) and 2-amino-3-methyl-imidazo[4,5-f ]quinoline (IQ), there was a significant decrease in mutagenesis evidenced by the number of His+ revertants in Salmonella typhymurium TA98. There was a statistically significant increase in the number of S. typhimurium His+ revertants induced by AFB₁ in the presence of hepatic microsomes from rats fed a HSD.; Glutathione-S-transferase (GST) enzymatic activity is essential for the elimination of products of the metabolism of xenobiotics and is found in the cytosol conjugating glutathione to other moieties rendering them more hydrophilic and excretable. In the sucrose fed rats the activity of GSTs was significantly decreased, suggesting that a HSD may alter the elimination of metabolites.