scholarly journals Quantitative analysis of metabolism of hepatic triglyceride in ethanol-treated rats

1976 ◽  
Vol 156 (1) ◽  
pp. 33-46 ◽  
Author(s):  
M A Abrams ◽  
C Cooper

An acute intraperitoneal injection of ethanol (0.7 or 2.1g/kg body wt.) causes the reversible, dose-dependent accumulation of hepatic triglyceride in rats. By using a pulse of [14C]palmitate injected into a tail vein, it was found that ethanol (2.1g/kg)had no effect on the flux of unesterified fatty acid of serum (4.3mumol/min per 100g body wt.). However, either dose increased the fraction of the total flux going to liver from 0.16 to0.27 as rapidly as could be measured (30s), and it remained elevated until all ethanol had been cleared from the blood. The fraction of the total radioactivity in lipids of liver that was in triglyceride increased linearly for 1 h from 30 to 50% and there was a simultaneous decrease in phospholipid from 60 to 40%. The rate of synthesis of hepatic triglyceride derived directly from unesterified fatty acid of serum was calculated by using the flux rate of unesterified fatty acid in serum, the fractional hepatic uptake of this flux, and the percentage of liver fatty acid esterified to triglyceride. This contribution is related to the total synthetic rate of hepatic triglyceride (rate of accumulation+rate of release) to determine quantitatively how much of the developing fatty liver is attributable to increased uptake of unesterfied fatty acid of serum. At the higher dose of ethanol, about half of the accumulating triglyceride is derived from this source, whereas with the lower dose of ethanol it can account for all of the build-up.

1976 ◽  
Vol 156 (1) ◽  
pp. 47-54 ◽  
Author(s):  
M A Abrams ◽  
C Cooper

Studies were made on the mechanism by which livers of ethanol-treated rats take up an increased fraction of the total flux of unesterified fatty acid in serum. It was found that ethanol (0.7g/kg) causes a twofold rise in the serum content of liver, and that this serum is in rapid equilibrium with the general circulation. The fractional hepatic uptake from serum of group of compounds with varying uptake mechanisms and metabolic fates was studied in control and ethanol-treated animals. All the compounds tested, including unesterified fatty acid, showed an enhanced uptake when ethanol was given. For one of the compounds, carbon tetrachloride, a dose/response relationship was established between the amount administered, the amount taken up by liver, and the amount metabolized. These findings were interpreted to mean that this dose of ethanol causes the liver to receive an increased flow of blood, and as a result all compounds present and capable of being taken by liver are taken up at an increased rate. Hepatic blood flow was measured by a technique that monitors the rate of clearance of a colloidal lipid emulsion. It was found that ethanol increased hepatic blood flow by about 60%. This effect of ethanol on hepatic blood flow provides an explanation for the fatty liver and the synergistic effect between an acute dose of ethanol and carbon tetrachloride. A hypothesis to explain why a moderate dose of ethanol causes triglyceride to accumulate in liver is presented.


1993 ◽  
Vol 265 (3) ◽  
pp. G547-G554
Author(s):  
C. A. Hinchman ◽  
A. T. Truong ◽  
N. Ballatori

To identify potential mechanisms for hepatic removal of circulating glutathione (GSH) conjugates, uptake and metabolism of S-2,4-dinitrophenylglutathione (DNP-SG) were examined in isolated perfused livers from rat and guinea pig. Guinea pig livers perfused with 5 mumol of DNP-SG in a recirculating system (50 microM initial concn) rapidly cleared the conjugate from the perfusate (half time 3.7 min), whereas clearance was considerably slower in rat liver (half time 35 min). Disappearance of DNP-SG from the perfusate was accompanied by a simultaneous appearance of DNP-SG and its metabolites in bile. Addition of acivicin, an inhibitor of gamma-glutamyltransferase (gamma-GT), to the perfusate resulted in a marked decrease in DNP-SG clearance by guinea pig liver but had no effect in rat liver, suggesting that in the guinea pig this process is largely dependent on sinusoidal gamma-GT activity. However, even in the presence of acivicin, rat and guinea pig livers removed nearly one-half of the administered DNP-SG from the recirculating perfusate over 30 min. High concentrations of DNP-SG were found in bile (up to 3.7 mM), indicating that the liver is capable of transporting the intact conjugate from the circulation. When rat livers were perfused with higher concentrations of DNP-SG (100 and 250 microM), biliary excretion of DNP-SG increased dose dependently, with concentrations in bile reaching 10 mM at the higher dose. This was accompanied by a dose-dependent choleresis.(ABSTRACT TRUNCATED AT 250 WORDS)


2015 ◽  
Vol 112 (4) ◽  
pp. 1143-1148 ◽  
Author(s):  
Daniel F. Vatner ◽  
Sachin K. Majumdar ◽  
Naoki Kumashiro ◽  
Max C. Petersen ◽  
Yasmeen Rahimi ◽  
...  

A central paradox in type 2 diabetes is the apparent selective nature of hepatic insulin resistance—wherein insulin fails to suppress hepatic glucose production yet continues to stimulate lipogenesis, resulting in hyperglycemia, hyperlipidemia, and hepatic steatosis. Although efforts to explain this have focused on finding a branch point in insulin signaling where hepatic glucose and lipid metabolism diverge, we hypothesized that hepatic triglyceride synthesis could be driven by substrate, independent of changes in hepatic insulin signaling. We tested this hypothesis in rats by infusing [U-13C] palmitate to measure rates of fatty acid esterification into hepatic triglyceride while varying plasma fatty acid and insulin concentrations independently. These experiments were performed in normal rats, high fat-fed insulin-resistant rats, and insulin receptor 2′-O-methoxyethyl chimeric antisense oligonucleotide-treated rats. Rates of fatty acid esterification into hepatic triglyceride were found to be dependent on plasma fatty acid infusion rates, independent of changes in plasma insulin concentrations and independent of hepatocellular insulin signaling. Taken together, these results obviate a paradox of selective insulin resistance, because the major source of hepatic lipid synthesis, esterification of preformed fatty acids, is primarily dependent on substrate delivery and largely independent of hepatic insulin action.


1990 ◽  
Vol 259 (5) ◽  
pp. E736-E750 ◽  
Author(s):  
R. C. Bonadonna ◽  
L. C. Groop ◽  
K. Zych ◽  
M. Shank ◽  
R. A. DeFronzo

Methodology for measuring plasma free fatty acid (FFA) turnover/oxidation with [1–14C]palmitate was tested in normal subjects. In study 1, two different approaches (720-min tracer infusion without prime vs. 150-min infusion with NaH14CO3 prime) to achieve steady-state conditions of 14CO2 yielded equivalent rates of plasma FFA turnover/oxidation. In study 2, during staircase NaH14CO3 infusion, calculated rates of 14CO2 appearance agreed closely with NaH14CO3 infusion rates. In study 3, 300-min euglycemic insulin clamp documented that full biological effect of insulin on plasma FFA turnover/oxidation was established within 60–120 min. In study 4, plasma insulin concentration was raised to 14 +/- 2, 23 +/- 2, 38 +/- 2, 72 +/- 5, and 215 +/- 10 microU/ml. A dose-dependent insulin suppression of plasma FFA turnover/oxidation was observed. Plasma FFA concentration correlated positively with plasma FFA turnover/oxidation in basal and insulinized states. Total lipid oxidation (indirect calorimetry) was significantly higher than plasma FFA oxidation in the basal state, suggesting that intracellular lipid stores contributed to whole body lipid oxidation. Hepatic glucose production and total glucose disposal showed the expected dose-dependent suppression and stimulation, respectively, by insulin. In conclusion, insulin regulation of plasma FFA turnover/oxidation is maximally manifest at low physiological plasma insulin concentrations, and in the basal state a significant contribution to whole body lipid oxidation originates from lipid pool(s) that are different from plasma FFA.


2003 ◽  
Vol 90 (6) ◽  
pp. 1071-1080 ◽  
Author(s):  
Samantha Kew ◽  
Edward S. Gibbons ◽  
Frank Thies ◽  
Gerald P. McNeill ◽  
Paul T. Quinlan ◽  
...  

The effects of altering the type of n-3 polyunsaturated fatty acid (PUFA) in the mouse diet on the ability of monocytes and neutrophils to perform phagocytosis were investigated. Male weanling mice were fed for 7 d on one of nine diets which contained 178 g lipid/kg and which differed in the type of n-3 PUFA and in the position of these in dietary triacylglycerol (TAG). The control diet contained 4·4 g α-linolenic acid/100 g total fatty acids. In the other diets, eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) replaced a proportion (50 or 100 %) of the α-linolenic acid, and were in the sn-2 or the sn-1(3) position of dietary TAG. There were significant increases in the content of n-3 PUFA in spleen-cell phospholipids when EPA or DHA was fed. These increases were largely independent of the position of EPA or DHA in dietary TAG except when EPA was fed at the highest level, when the incorporation was greater when it was fed in the sn-2 than in the sn-1(3) position. There was no significant effect of dietary DHA on monocyte or neutrophil phagocytic activity. Dietary EPA dose-dependently decreased the number of monocytes and neutrophils performing phagocytosis. However, when EPA was fed in the sn-2 position, the ability of active monocytes or neutrophils to engulf bacteria was increased in a dose-dependent fashion. This did not occur when EPA was fed in the sn-1(3) position. Thus, there appears to be an influence of the position of EPA, but not of DHA, in dietary TAG on its incorporation into cell phospholipids and on the activity of phagocytic cells.


2017 ◽  
Vol 11 (1) ◽  
pp. 14-22
Author(s):  
Gábor Molnár ◽  
Andor Scholtz ◽  
Róbert Vass

In this paper the rate of accumulation was studied along four VO floodplain cross sections of the UpperTisza region between 1974 and 2014. VO floodplain cross sections are based on a mapping base-point grid (established in 1890), and they are located a few kilometers from each other. Furthermore, the roughness changes of different surface types, crossed by the VO floodplain cross-sections, were also determined between 1965 and 2015. The accumulation studies were extended to include the accumulation rates of the cut off meanders located along and/or close to the VO cross-sections. The roughness values increased in all four floodplain VO cross-sections since 1965; in two of them it reached or approximated 100 %. The average accumulation along the VO cross-sections was between 28 and 47 cm (0.73–1.23 cm/year) during the 38-year period. However, its areal distribution showed large differences. The highest values (169–309 cm, i.e. 4.44–8.13 cm/year) were found at the lowest points of the cut off meanders and swales in every case. The accumulation rate of the examined three cut off meanders near the floodplain cross-sections (140 and 1570 meters from the river bed) was lower (0.84–2.5 cm/year), but the study period was significantly longer (154 and 161 years, respectively). Comparing the values of the two periods, it is obvious that the accumulation of the active floodplain accelerates, presumably due to the significant increase of surface roughness.


1931 ◽  
Vol 8 (2) ◽  
pp. 133-150
Author(s):  
F. C. STOTT

1. The spring inshore migration of Echinus at Port Erin in 1930 started in early February and reached its maximum in the middle of March. Mature gonads were found at the end of February and throughout March and early April. At the end of June all gonads examined were spent. The sea temperature throughout this period was observed. It is probable that May was the chief month in which natural spawning took place. 2. A cycle of changes in the composition of the gonad are recorded from November 1929 to July 1930. The chief of these are: (a) In the males an increase in percentage dry weight as the gonads mature ; the opposite taking place in the females. (b) A large and simultaneous decrease in percentage glycogen in both male and female gonads prior to spawning followed by a great post-spawning increase. The fatty acid content does not alter with the maturation of the gonad, but an indication is given that an increase in the percentage of carbohydrates other than glycogen occurs. Hence it is suggested that glycogen is transformed in the maturing gonad into carbohydrate food reserves for the ripe eggs and sperm.


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