bfamilies Erlotinib mechanism of action suggests that the dif fering capacities of these European sea bass half sibfamilies to grow on a vegetable diet are not due to differing capacities to synthesize LC PUFA. Sterol metabolism The present microarray data also indicate an increase in expression levels of genes involved in sterol metabolism in VD fed fish. Among these, isopentenyl diphosphate delta isomerase 1, lanosterol 14 alpha demethylase, farnesyl pyrophosphate synthase, c 4 methylsterol oxidase and 3 hydroxy 3 methyl glutaryl coenzyme A reductase genes are known to be implicated in the cholesterol metabolic pathway. More particularly, HMGCR, a trans membrane glycoprotein involved in the rate limiting step of sterol biosynthesis, is increased, as shown in mammals.

The stimulation of cholesterol biosynth esis in Inhibitors,Modulators,Libraries fish fed VD could be related to the difference in sterol composition between diets. Indeed, while the fish diet is rich in cholesterol, the vegetable diet used in this experiment Inhibitors,Modulators,Libraries contains exclusively plant sterols, which have been shown to affect membrane properties by decreasing permeability and fluidity, and modifying Inhibitors,Modulators,Libraries phospholipid order in mammals. As a conse quence, the increase in cholesterol biosynthesis could be a metabolic response to its deficiency in the diet, as well as a way to restore membrane properties by incorpora tion of endogenous cholesterol. Since we did not mea sure the cholesterol content in the liver, flesh or blood, it is not possible for us to assess the capacity of Eur opean sea bass to compensate for possible dietary defi ciencies in cholesterol through a regulation of its biosynthesis.

Moreover, similarly to the LC PUFA path way, no significant difference of cholesterol biosynthetic regulation was observed between the half sibfamilies. Interestingly, several VD stimulated genes involved in the lipogenic pathway are known to be molecular targets of sterol regulatory ele ment binding proteins, which are key regula Inhibitors,Modulators,Libraries tors of fatty acid and cholesterol synthesis. Recent data indicating an up regulation of the srebp 1 gene expression in European sea bass fed a vegetable diet could thus be due to such stimulations. Lipid and sterol transport The present microarray data indicate that the stimula tion of genes involved in fatty acid and cholesterol synthesis in VD fed fish was associated with an over expression of genes involved in their transport, such as apolipoproteins APOA1 and APOB100, which are the major protein constituents of high and low density lipo protein, GSK-3 respectively.

The LDL, including APOB100, are involved in the transport of cholesterol and lipids from the liver to other tissues. Thus, up regulation of apob100 combined with the induction of the expression selleck chem of lipoprotein lipase, a key enzyme involved in the hydrolysis of triglyceride, suggests an increase in lipid transport and metabolism from the liver to tissues in fish fed VD. The decrease in angiopoietin related protein 3 that we observed in fish fed VD reinforces this idea sin