Gene expression modulation of liver energy metabolism by oleoyl-oestrone in overweight rats

We intended to determine how the liver copes with the massive handling of lipids induced by OE (oleoyl-oestrone), as well as to characterize and differentiate the actual OE effects from those that may be only the consequence of decreased food intake. Thus we used male rats treated with oral OE (10 nmol/g per day) compared with a vehicle only PF (pair-fed) group and controls fed ad libitum (vehicle only). Plasma parameters, and total liver lipids, glycogen, DNA and total mRNA were measured. RNA was extracted and used for real-time PCR analysis of the gene expression of enzymes and regulatory factors of liver energy metabolism. Most hepatic proteins showed similar gene expressions in OE and controls, but the differences widened between OE and PF rats, showing that OE effects could not be merely attributed to a lower energy intake. The liver of OE-treated rats largely maintained its ability to mobilize glucose for the synthesis of fats; this was achieved in part by a peculiar combination of regulative modifications that facilitate both fatty acid disposal and restrained glucose utilization under conditions of limited food supply but ample availability of internal energy stores. In conclusion, the results presented suggest that the effect of OE on liver metabolism may be (at least in part) mediated through an insulin-sensitivity-dependent modulation of the expression of SREBP-1c (sterol-regulatory-element-binding protein-1c), resulting in the unique combined effect of mildly increased (or maintained) glucose disposal but also limited enhancement of lipogenesis.