Lack of plasma albumin impairs intravascular lipolysis and explains the associated free fatty acids deficiency and hypertriglyceridemia

Background: Abnormalities in lipid metabolism and transport are hallmarks in analbuminemic Nagase rats (NAR) and humans. Triglyceridemia is nearly 3- to 5-fold higher in female NAR than in control Sprague-Dawley rats (SDR). Also, NAR present with a severe plasma free fatty acid (FFA) deficit. There are conflicting results regarding the mechanisms underlying NAR hypertriglyceridemia. Objective: We aimed at investigating whether liver lipogenesis and triglyceride secretion rates into the plasma contribute to the hypertriglyceridemia in NAR. We also studied whether heparin or albumin administration would release the hypothesized lipolysis inhibition in NAR. Methods: The incorporation of tritiated water into lipids and the linear accumulation rate of plasma triglycerides after Triton WR1339 injection were the measures of liver lipogenesis and triglyceride secretion rates. Results: Lipogenesis (596 +/- 40 vs. 929 +/- 124 mu mol (H2O)-H-3/g/h) and triglyceride (4.25 +/- 1.00 vs. 7.04 +/- 1.68 mg/dL/min) secretion rates were slower (P <= 0.05) in fasted NAR than in control SDR. The injection of either heparin or albumin elicited an increase in NAR plasma FFA levels over time. FFA levels reached control levels 90 min after the albumin administration, increasing from 0.36 +/- 0.05 to 1.34 +/- 0.16 mEq/L (P <= 0.05). These results indicate that the lack of plasma albumin inhibits intravascular lipolysis and causes the FFA deficit observed in NAR. Conclusion: NAR hepatic triglyceride synthesis and output do not contribute to NAR hypertriglyceridemia. We propose that the lack of albumin diminishes intravascular lipolysis which reduces the plasma triglyceride removal rate and explain both NAR hypertriglyceridemia and FFA deficiency.