Hypertriglyceridemia associated with
chronic renal failure (CRF) and elevated plasma concentration of
very-low-density lipoprotein (VLDL) are thought to be a consequence of the depressed
lipoprotein lipase and hepatic
lipase activities and impaired clearance of
lipoproteins. However, there is some evidence that the
lipoproteins overproduction might also contribute to
hypertriglyceridemia in CRF. This study was performed to test the hypothesis that the increased rate of lipogenesis consequent to upregulation of
fatty acid synthase (FAS), a key lipogenic
enzyme, gene expression could contribute to overproduction of
triacylglycerols and to
hypertriglyceridemia in CRF. FAS activity, FAS
protein mass (Western blot analysis), and FAS
mRNA level (Northern blot analysis) in liver and epididymal white adipose tissue (WAT) were measured in male Wistar rats 6 weeks after subtotal (5 of 6)
nephrectomy or
sham operation. Moreover, the rate of lipogenesis in WAT was determined. The CRF group showed significant increase in FAS gene expression (measured as activity,
mRNA, and
protein abundance) in both liver and WAT. This was associated with the increase in the lipogenesis rate and with the increase in plasma
triacylglycerol and VLDL concentrations. Our results suggest that not only decreased removal, but also an increase of
triacylglycerol production could contribute, in part, to the CRF-associated
hyperlipidemia. Upregulation of FAS gene expression, shown in this report for the first time, reveals another factor involved in disturbed lipid metabolism in CRF. It seems that elevated plasma
insulin and
cytokine concentration could play an important role in the mechanism responsible for the increased FAS gene expression in CRF.