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

Abstract

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.

Aberrant Hepatic Expression of PPARγ2 Stimulates Hepatic Lipogenesis in a Mouse Model of Obesity, Insulin Resistance, Dyslipidemia, and Hepatic Steatosis

“…The basis for accumulation of TG in the liver is complex and can include reduced assembly and secretion of VLDL because of defects in the synthesis of apoB (31) or in microsomal triglyceride transfer protein activity (32). However, VLDL assembly and secretion are typically increased above normal in animals (3,4,(33)(34)(35) and people (36 -39) with insulin resistance, diabetes mellitus, and hepatic steatosis, suggesting that other abnormalities are playing key roles.…”

Short‐term hormonal control of hepatic carbohydrate and lipid catabolism

“…In general, the alterations in lipid metabolism in obese rodents are less susceptible to reversal by food deprivation than are those in carbohydrate metabolism. This is true for example of the increases in hepatic lipogenesis [6], plasma turnover of triglyceride, free fatty acid and glycerol [56,57] and utilisation of plasma triglyceride by tissues [58] which are observed in genetically obese mice.…”

Fatty acid synthesis in the regenerating liver of the rat

“…Incorporation of 3H into lipids is linear with time over 1 h (Lowenstein, 1971, so that this technique provides a valid measure of the rate of fatty acid synthesis. Liver glycogen (Salmon et al, 1974) and total fat content (Salmon & Hems, 1973) were measured. Blood was rapidly removed by cardiac puncture from the stunned rats, and serum was prepared for analysis of free fatty acids and total triacylglycerol (Salmon & Hems, 1973).…”

“…Liver glycogen (Salmon et al, 1974) and total fat content (Salmon & Hems, 1973) were measured. Blood was rapidly removed by cardiac puncture from the stunned rats, and serum was prepared for analysis of free fatty acids and total triacylglycerol (Salmon & Hems, 1973). Radioactivity was measured in fatty acid classes separated by degree of saturation (Salmon et al, 1974).…”