Plasma lipoproteins and the synthesis and turnover of plasma triglyceride in normal and genetically obese mice.

1. Lipoproteins in the plasma of mice were characterized by agarose-gel chromatography and polyacrylamide-gel electrophoresis: genetically obese (ob/ob) mice exhibited hyperlipoproteinaemia (compared with lean mice), largely owing to an increase in the concentration of cholesterol in high-density lipoprotein. Plasma concentrations of triglyceride and phospholipid were not markedly increased in genetically obese mice. 2. The formation of glycerolipids in liver and plasma was investigated with (14)C-labelled precursors. The synthesis of hepatic triglyceride and phospholipid from glucose or palmitate was enhanced in ob/ob mice, compared with lean mice. The rate of entry of triglyceride into plasma, calculated from the time-course of incorporation of (14)C from [(14)C]palmitate into plasma triglyceride, was increased in ob/ob mice (0.5mumol of fatty acid/min, compared with 0.2 in lean mice). 3. The removal from plasma of murine lipoprotein triglyceride-[(14)C]fatty acid was increased in ob/ob mice (half-time 2.2min, compared with 7.2min in lean mice). Similar results were obtained with an injected lipid emulsion (Intralipid). 4. From these measurements, estimates of the rates of turnover of plasma triglyceride in mice (fed on a mixed diet, female, 3 months old) are about 1.0mumol of fatty acid/min in ob/ob mice, and 0.25 in lean mice. 5. The major precursor of hepatic and plasma triglyceride in lean and ob/ob mice was calculated to be plasma free fatty acid. 6. These results are discussed, in connexion with the role of the liver in triglyceride metabolism in mice, especially in relation to genetic obesity.