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Altered interactions between lipogenesis and fatty acid oxidation in regenerating rat liver.

ABSTRACT: The concentrations of malonyl-CoA, citrate, ketone bodies and long-chain acylcarnitine were measured in freeze-clamped liver samples from fed or starved normal, partially hepatectomized or sham-operated rats. These parameters were used in conjunction with measurements of the concentration of plasma non-esterified fatty acids and the rates of hepatic lipogenesis to obtain correlations between rates of fatty acid delivery to the liver, lipogenesis and fatty acid oxidation to ketone bodies and CO2. These correlations indicated that the development of fatty liver after partial hepatectomy is due to an increased partitioning of long-chain acyl-CoA towards acylglycerol synthesis and away from acylcarnitine formation. However, this did not appear to be due to an altered relationship between hepatic malonyl-CoA concentration and acylcarnitine formation. For any concentration of long-chain acylcarnitine, the concentrations of both hepatic and blood ketone bodies were significantly lower in partially hepatectomized rats than in normal or sham-operated animals. This indicated that a lower proportion of the product of beta-oxidation was used for ketone-body formation and more for citrate synthesis in the regenerating liver, especially during the first 24 h after resection. This inference was supported by the changes in hepatic citrate concentrations observed. The high rates of lipogenesis that occurred in the liver remnant were accompanied by an altered relationship between lipogenic rate and hepatic malonyl-CoA concentration, such that much lower concentrations of malonyl-CoA were associated with any given rate of lipogenesis. These adaptations are discussed in relation to the requirements by the remnant for high rates of energy formation through the tricarboxylic acid cycle during the first 24 h after resection, and the possibility that cycling between fatty acid oxidation and synthesis may occur to a greater degree in regenerating liver.

SUBMITTER: Schofield PS

PROVIDER: S-EPMC1147584 | biostudies-other | 1987 Jan

REPOSITORIES: biostudies-other

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Project description:BACKGROUND:Biochemical evidence has linked the coordinate control of fatty acid (FA) synthesis with the activity of stearoyl-CoA desaturase-1 (SCD1). The ratio of 16:1n-7 to 16:0 [SCD1??] in plasma triacylglycerol FA has been used as an index to reflect liver SCD1?? activity and has been proposed as a biomarker of FA synthesis, although this use has not been validated by comparison with isotopically measured de novo lipogenesis (DNL(Meas)). OBJECTIVE:We investigated plasma lipid 16:1n-7 and FA indexes of elongation and desaturation in relation to lipogenesis. DESIGN:In this cross-sectional investigation of metabolism, 24 overweight adults, who were likely to have elevated DNL, consumed D2O for 10 d and had liver fat (LF) measured by magnetic resonance spectroscopy. Very-low-density lipoprotein (VLDL)-triacylglycerols and plasma free FA [nonesterified fatty acids (NEFAs)] were analyzed by using gas chromatography for the FA composition (molar percentage) and gas chromatography-mass spectrometry and gas chromatography-combustion isotope ratio mass spectrometry for deuterium enrichment. RESULTS:In all subjects, VLDL-triacylglycerol 16:1n-7 was significantly (P < 0.01) related to DNL(Meas) (r = 0.56), liver fat (r = 0.53), and adipose insulin resistance (r = 0.56); similar positive relations were shown with the SCD1?? index, and the pattern in NEFAs echoed that of VLDL-triacylglycerols. Compared with subjects with low LF (3.1 ± 2.7%; n = 11), subjects with high LF (18.4 ± 3.6%; n = 13) exhibited a 45% higher VLDL-triacylglycerol 16:1n-7 molar percentage (P < 0.01), 16% of subjects had lower 18:2n-6 (P = 0.01), and 27% of subjects had higher DNL as assessed by using a published DNL index (ratio of 16:0 to 18:2n-6; P = 0.03), which was isotopically confirmed by DNL(Meas) (increased 2.5-fold; P < 0.01). Compared with 16:0 in the diet, the low amount of dietary 16:1n-7 in VLDL-triacylglycerols corresponded to a stronger signal of elevated DNL. CONCLUSION:The current data provide support for the use of the VLDL-triacylglycerol 16:1n-7 molar percentage as a biomarker for elevated liver fat when isotope use is not feasible; however, larger-scale confirmatory studies are needed.

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Altered interactions between lipogenesis and fatty acid oxidation in regenerating rat liver.

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