Synthesis of fatty acids in the perfused mouse liver

Abstract

1. Fatty acid synthesis de novo was measured in the perfused liver of fed mice. 2. The total rate, measured by the incorporation into fatty acid of (3)H from (3)H(2)O (1-7mumol of fatty acid/h per g of fresh liver), resembled the rate found in the liver of intact mice. 3. Perfusions with l-[U-(14)C]lactic acid and [U-(14)C]glucose showed that circulating glucose at concentrations less than about 17mm was not a major carbon source for newly synthesized fatty acid, whereas lactate (10mm) markedly stimulated fatty acid synthesis, and contributed extensive carbon to lipogenesis. 4. The identification of 50% of the carbon converted into newly synthesized fatty acid lends further credibility to the use of (3)H(2)O to measure hepatic fatty acid synthesis. 5. The total rate of fatty acid synthesis, and the contribution of glucose carbon to lipogenesis, were directly proportional to the initial hepatic glycogen concentration. 6. The proportion of total newly synthesized lipid that was released into the perfusion medium was 12-16%. 7. The major products of lipogenesis were saturated fatty acids in triglyceride and phospholipid. 8. The rate of cholesterol synthesis, also measured with (3)H(2)O, expressed as acetyl residues consumed, was about one-fourth of the basal rate of fatty acid synthesis. 9. These results are discussed in terms of the carbon sources of hepatic newly synthesized fatty acids, and the effect of glucose, glycogen and lactate in stimulating lipogenesis, independently of their role as precursors.

Fatty acid synthesis in the regenerating liver of the rat

“…The total amount of newly synthesized fatty acid in tissues was calculated from the incorporation of 3H from 3H20, and is expressed as mol of C2 units converted into fatty acids, taking a factor of2.4 as the discrimination against 3H compared with "H (Windmueller & Spaeth, 1966;Lowenstein, 1971;Salmon et al, 1974 …”

“…Solvents (Salmon et al, 1974;Hems et al, 1975). 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.…”

“…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).…”

“…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). Livers of red rats were perfused as previously described (Kirk et al, 1976).…”

Effect of fasting on the Cori cycle in rats

“…If we assume that the difference between the rate of lactate turnover and the rate of lactate oxidation represents the rate of gluconeogenesis from lactate there is a 15 to 40% underestimation of this rate in these conditions. It is more difficult to discuss the data obtained in the control and the fasted-refed animals as in these conditions lactate can be used in other pathways than oxidation and gluconeogenesis such as glycogenesis and/or lipogenesis [ 15,16].…”