Alanine as a lipogenic precursor in isolated hepatocytes from obese Zucker rats

Isolated hepatocytes from obese Zucker rats showed an increased capacity for lipid synthesis measured as the incorporation of 3H2O into lipid fractions. In addition lipid synthesis from 1 mM U-14C-alanine was elevated as compared to those isolated from their lean counterparts. On these lines, the amino acid was a better lipogenic substrate than U-14C-lactate at 5 mM concentration. Insulin increased lipid synthesis from the amino acid in the lean animals while showed no effects on this parameter in the obese. While the hepatocytes from the lean animals used to a similar extent U-14C-alanine carbon from 14CO2 production, lipid synthesis and 14C-glycogen incorporation, those from the obese animals showed a decreased oxidation and glycogen incorporation while an augmented lipid synthesis. The total amount of the amino acid taken up by the obese animals was also significantly elevated. Conversely, the metabolic fate of U-14C-leucine was very similar between the two groups. It can be concluded that in the obese Zucker rat alanine is a very important amino acid which contributes to sustain the high liver hyperlipogenesis previously described.