Hepatic Adenosine Triphosphate Content Research Articles

Regulation of mitochondrial biosynthesis and function by dietary carbohydrate levels and lipid sources in juvenile blunt snout bream Megalobrama amblycephala

This study aimed to investigate the effects of dietary non-protein energy adjustments on the mitochondrial biosynthesis and function of juvenile Megalobrama amblycephala. Fish (average weight: 37.98 ± 0.07 g) were fed eight diets containing two dietary carbohydrate levels (30% and 43%) and four lipid sources (fish oil, soybean oil, palm oil and the mixed oil) for 11 weeks. Liver mitochondrial respiratory chain complex V activity and ATP (adenosine triphosphate) content both increased significantly with increasing dietary carbohydrate levels, whereas the opposite was true for the AMP (adenosine 5′-monophosphate)/ATP ratio, hepatic transcripts of AMP-activated protein kinase α1 (AMPKα1), AMPKα2, peroxisome proliferators γ-activated receptor coativator-1α (PGC-1α), NADH dehydrogenase 1 and cytochrome c oxidase 1 (COX1) as well as the activities of Na+-K+-ATPase, succinate dehydrogenase (SDH), citrate synthase (CS) and mitochondrial respiratory chain complex I, III and IV. Additionally, hepatic ATP content, the transcripts of AMPKα, COX1 and ATP6 and the activities of Na+-K+-ATPase, SDH, CS and mitochondrial respiratory chain complex III were all significantly affected by lipid sources. Furthermore, an interaction between dietary carbohydrate levels and lipid sources was also observed in the activities of liver mitochondrial Na+-K+-ATPase and respiratory chain complex III as well as the transcripts of ATP6 and PGC-1α. Overall, these findings suggested that dietary carbohydrate levels and lipid sources remarkably affected the mitochondrial biosynthesis and function of M. amblycephala. A diet containing 30% carbohydrate and FO could boost its mitochondrial biosynthesis, while that of 30% carbohydrate and SO could enhance the mitochondrial function.

Higher dietary fructose is associated with impaired hepatic adenosine triphosphate homeostasis in obese individuals with type 2 diabetes.

Fructose consumption predicts increased hepatic fibrosis in those with nonalcoholic fatty liver disease (NAFLD). Because of its ability to lower hepatic adenosine triphosphate (ATP) levels, habitual fructose consumption could result in more hepatic ATP depletion and impaired ATP recovery. The degree of ATP depletion after an intravenous (IV) fructose challenge test in low- versus high-fructose consumers was assessed. We evaluated diabetic adults enrolled in the Action for Health in Diabetes Fatty Liver Ancillary Study (n = 244) for whom dietary fructose consumption estimated by a 130-item food frequency questionnaire and hepatic ATP measured by phosphorus magnetic resonance spectroscopy and uric acid (UA) levels were performed (n = 105). In a subset of participants (n = 25), an IV fructose challenge was utilized to assess change in hepatic ATP content. The relationships between dietary fructose, UA, and hepatic ATP depletion at baseline and after IV fructose challenge were evaluated in low- (<15 g/day) versus high-fructose (≥ 15 g/day) consumers. High dietary fructose consumers had slightly lower baseline hepatic ATP levels and a greater absolute change in hepatic α-ATP/ inorganic phosphate (Pi) ratio (0.08 versus 0.03; P = 0.05) and γ-ATP /Pi ratio after an IV fructose challenge (0.03 versus 0.06; P = 0.06). Patients with high UA (≥ 5.5 mg/dL) showed a lower minimum liver ATP/Pi ratio postfructose challenge (4.5 versus 7.0; P = 0.04). High-fructose consumption depletes hepatic ATP and impairs recovery from ATP depletion after an IV fructose challenge. Subjects with high UA show a greater nadir in hepatic ATP in response to fructose. Both high dietary fructose intake and elevated UA level may predict more severe hepatic ATP depletion in response to fructose and hence may be risk factors for the development and progression of NAFLD.

Correlation between adenosine triphosphate content and apoptosis in liver of rats treated with alcohol.

Chronic alcohol consumption depresses adenosine triphosphate (ATP) synthesis and induces mitochondrial DNA (Mt-DNA) deletion. ATP content in cells may play a critical role in inducing cell death, apoptosis, or necrosis. However, it is unknown which type of cell death occurs in alcoholic liver disease. In this study, the deletions of hepatic Mt-DNA, hepatic ATP content, and the number of single-stranded DNA (ss-DNA) of hepatocytes in rats treated with ethanol were determined to elucidate the relationship among Mt-DNA deletion, ATP synthesis, and/or hepatic apoptosis. Sixteen male Wistar rats were fed with a liquid diet containing 36% ethanol (E group) or liquid diet without ethanol (C group) for 5 weeks. Hepatic ATP content was measured and the deletions of Mt-DNA encoding complexes I, IV, and V were determined in fresh liver tissue, and ss-DNA was stained in paraffin sections. Fatty change was observed in the E group, but not in the C group. Hepatic ATP content in the E group was 0.44 micromol/g of liver, which was significantly lower than that in the C group (0.84 micromol/g of liver). However, no deletion of Mt-DNA encoding complexes I, IV, and V was detected in either the E or the C group. ss-DNA staining was clearly observed in the nuclei of hepatocytes in both groups. The number of ss-DNA-positive hepatocytes in the E group was 5.6 +/- 1.8/10,000 hepatocytes, which was significantly less than that in the C group: 20.6 +/- 4.8/10,000 hepatocytes. There was a positive correlation between hepatic ATP contents and the number of ss-DNA-positive cells. The results suggest that mitochondrial function, at least in part ATP synthesis, was depressed before the damage of Mt-DNA by chronic ethanol consumption. Chronic ethanol consumption may not be responsible for the apoptosis of hepatocytes.

Cold preservation injury in rat liver: effect of liposomally-entrapped adenosine triphosphate

Background/Aims: Energy charge and capacity for adenosine triphosphate (ATP) synthesis have been demonstrated to play a major role in the maintenance of organ function after liver preservation for transplantation. The aim of this study was to evaluate whether a supply of liposomally-entrapped ATP during preservation could improve the energy state and metabolism of cold-stored rat liver. Methods: In the first set of experiments, the uptake of ATP-containing liposomes and their effects on hepatic viability were determined in isolated perfused unstored rat liver. In the second set of experiments, rat livers were preserved for 18 h at 4°C in UW solution in the presence of these liposomes, and effects on energy state, cell volume and metabolism were evaluated. In each part, data were compared with adequate control, unloaded liposome-treated, and free ATP-treated groups ( n=6 in each group). Results: In non-stored livers, ATP-containing liposomes were taken up by the liver; they did not alter hepatic viability and induced a decrease in energy substrate consumption (glucose and amino acids), and an improvement in intrahepatic ATP content (+23% vs. Control). Addition of liposomally-entrapped ATP during cold storage produced a significant attenuation of the decrease in hepatic ATP content (Lip ATP 2: 524±45 vs. Control 2: 364±106 nmol/g; p<0.05), and induced, during reperfusion, a decrease in proteolysis associated with an increase in cell volume compared with the other groups (Lip ATP 2: 633±63 vs. Control 2: 532±38, Unloaded Lip 2: 483±55 and Free ATP 2: 500±29 μl/g; p<0.01). Conclusions: These data indicate that liposomally-entrapped ATP represents an effective means to improve liver graft energy state and function. The decrease in protein degradation may be related to the modification of cell volume.

Improvement of survival from hemorrhagic shock by enterectomy in rats: finding to implicate the role of the gut for irreversibility of hemorrhagic shock.

This study used a Wiggers shock model to investigate the effect of the removal of the intestines on the outcome of hemorrhagic shock. Rats were subjected to laparotomy for the removal of the entire small and large intestines (experimental group) or a sham operation (control group) before bloodshedding. During the period of shock, animals were maintained at 30-35 mm Hg arterial pressure for 2 hours. After reinfusion of the shed blood, rats were observed for over 3 hours for survival. The average volumes (mean +/- SEM) of shed blood were 6.84 +/- 0.23 mL (experimental group) and 6.49 +/- 0.39 mL (control group), with no significant difference between the two (p > 0.05). This protocol resulted in a 42% mortality (11 of 26) in the control group and 0% mortality (0 of 25) in the experimental group (p < 0.005, chi2). Moreover, in the survivors, the mean arterial pressure was significantly lower in the control (65.7 +/- 4.3 mm Hg) than in the experimental group (78.2 +/- 3.5 mm Hg) at the end of the experiment (p < 0.05). Comparing volume status, neither serial hematocrit values nor body weight changes through the experiment had a significant difference between the two groups (p's > 0.05). Serial quantitation of blood levels of tumor necrosis factor-alpha (TNF-alpha) revealed that systemic TNF-alpha concentrations peaked at 4 hours after shock in both groups. TNF-alpha levels were not reduced by enterectomy. Instead, the peak concentrations were significantly higher in the enterectomized (387.5 +/- 36.5 pg/mL, n = 13) than in the sham-enterectomized group (175.7 +/- 35.9 pg/mL, n = 12,p < 0.001). Limulus assay, used to detect endotoxins in the blood at 2 hours after restoration of blood volume, showed no endotoxemia in any specimen from either group. Four hours after hemorrhagic shock, blood levels of platelet-activating factor, quantitated by the radioimmunoassay method, were 2.88 +/- 0.18 ng/mL (experimental group, n = 8) and 2.32 +/- 0.32 ng/mL (control group, n = 6). The difference between these two means was not significant (p > 0.05). Measurement of hepatic adenosine triphosphate (ATP) by the luminometric method showed that hepatic ATP contents were significantly reduced in both groups after shock (p's < 0.05). However, a higher magnitude of hepatic ATP depletion occurred in the control group; significantly lower amounts of ATP in the liver tissues of the sham-enterectomized group (367 +/- 95 nmol/g, n = 7) than in that of the enterectomized group (870 +/- 100 nmol/g, n = 13) were observed at 5 hours after shock (p < 0.05). These experimental findings show that, in the absence of the intestines, hemorrhagic shock is associated with both an improved outcome and higher hepatic ATP levels in rats, suggesting the importance of intestinal participation in the process leading to hepatic ATP depletion as well as irreversibility in shock.

Effect of Alanine on D–Galactosamine–Induced Acute Liver Failure in Rats

The effect of high–dose alanine on survival and liver function in rats with acute liver failure caused by a lethal dose of d–galactosamine (d–gal) was studied. Greater than 90% of control animals died within 5 days after d–gal injection, but alanine significantly decreased mortality, even when treatment was started at 12 hours after d–gal injection. Alanyl–glutamine had a slight effect, but glucose produced no improvement. There was marked elevation of the plasma aspartate transaminase (AST) level, prolongation of the prothrombin time, and a decrease of the arterial ketone body ratio (AKBR) and hepatic adenosine triphosphate (ATP) content within 12 hours after d–gal injection. The AKBR decreased in parallel with the decrease of the hepatic ATP content. These parameters were significantly improved in alanine– treated rats at 48 hours after the induction of liver damage, which was just before control rats began to die. The hepatic ATP content was significantly greater in alanine–treated rats than in the other rats (including normal controls), but glucose pretreatment had no effect. It was also found that the liver labeling index of partially hepatectomized rats was significantly elevated by alanine administration at 3 hours before measurement. In conclusion, alanine is effective for the treatment of experimental acute liver failure, probably caused by promotion of ATP synthesis. Ala may be a good candidate for clinical application because of its preventive effect on hepatocyte necrosis and its promotive effect on liver regeneration.

Effect of alanine on D-galactosamine-induced acute liver failure in rats

The effect of high-dose alanine on survival and liver function in rats with acute liver failure caused by a lethal dose of D-galactosamine (D-gal) was studied. Greater than 90% of control animals died within 5 days after D-gal injection, but alanine significantly decreased mortality, even when treatment was started at 12 hours after D-gal injection. Alanyl-glutamine had a slight effect, but glucose produced no improvement. There was marked elevation of the plasma aspartate transaminase (AST) level, prolongation of the prothrombin time, and a decrease of the arterial ketone body ratio (AKBR) and hepatic adenosine triphosphate (ATP) content within 12 hours after D-gal injection. The AKBR decreased in parallel with the decrease of the hepatic ATP content. These parameters were significantly improved in alanine- treated rats at 48 hours after the induction of liver damage, which was just before control rats began to die. The hepatic ATP content was significantly greater in alanine-treated rats than in the other rats (including normal controls), but glucose pretreatment had no effect. It was also found that the liver labeling index of partially hepatectomized rats was significantly elevated by alanine administration at 3 hours before measurement. In conclusion, alanine is effective for the treatment of experimental acute liver failure, probably caused by promotion of ATP synthesis. Ala may be a good candidate for clinical application because of its preventive effect on hepatocyte necrosis and its promotive effect on liver regeneration. (Hepatology 1996 Nov;24(5):1211-6)