Intense exercise induces the degradation of adenine nucleotide and purine nucleotide synthesis via de novo pathway in the rat liver

Mikami, Toshio; Kitagawa, Jun

doi:10.1007/s00421-005-0106-4

Cited by 8 publications

(9 citation statements)

References 30 publications

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“…This notion is reinforced by findings that hepatic AMPK phosphorylation is increased following exercise (11,33,34) and fasting (34,35). The existing literature on changes in liver adenine nucleotides in response to metabolic stressors is difficult to interpret (22,(36)(37)(38)(39)(40)(41)(42)(43). Previous studies in rats have generally reported stress-induced reductions in hepatic ATP (36)(37)(38)(39)(40)(41)(42)(43), although one study found that this did not occur in response to varying fast durations (22).…”

Section: Figurementioning

confidence: 99%

“…The existing literature on changes in liver adenine nucleotides in response to metabolic stressors is difficult to interpret (22,(36)(37)(38)(39)(40)(41)(42)(43). Previous studies in rats have generally reported stress-induced reductions in hepatic ATP (36)(37)(38)(39)(40)(41)(42)(43), although one study found that this did not occur in response to varying fast durations (22). A number of these earlier studies have also shown that hepatic AMP levels increase in response to stress (22,36,37,41), while others have reported no change (42,43).…”

Section: Figurementioning

confidence: 99%

“…Previous studies in rats have generally reported stress-induced reductions in hepatic ATP (36)(37)(38)(39)(40)(41)(42)(43), although one study found that this did not occur in response to varying fast durations (22). A number of these earlier studies have also shown that hepatic AMP levels increase in response to stress (22,36,37,41), while others have reported no change (42,43). Many of these earlier studies do not report ADP and/or AMP levels (38)(39)(40), estimate adenine nucleotide concentrations using enzymatic methods (22, 36-40, 42, 43), or report reductions in TAN (41), thus complicating a full assessment of the energy state.…”

Section: Figurementioning

confidence: 99%

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Hepatic energy state is regulated by glucagon receptor signaling in mice

et al. 2009

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The hepatic energy state, defined by adenine nucleotide levels, couples metabolic pathways with energy requirements. This coupling is fundamental in the adaptive response to many conditions and is impaired in metabolic disease. We have found that the hepatic energy state is substantially reduced following exercise, fasting, and exposure to other metabolic stressors in C57BL/6 mice. Glucagon receptor signaling was hypothesized to mediate this reduction because increased plasma levels of glucagon are characteristic of metabolic stress and because this hormone stimulates energy consumption linked to increased gluconeogenic flux through cytosolic phosphoenolpyruvate carboxykinase (PEPCK-C) and associated pathways. We developed what we believe to be a novel hyperglucagonemic-euglycemic clamp to isolate an increment in glucagon levels while maintaining fasting glucose and insulin. Metabolic stress and a physiological rise in glucagon lowered the hepatic energy state and amplified AMP-activated protein kinase signaling in control mice, but these changes were abolished in glucagon receptor-null mice and mice with liver-specific PEPCK-C deletion. 129X1/Sv mice, which do not mount a glucagon response to hypoglycemia, displayed an increased hepatic energy state compared with C57BL/6 mice in which glucagon was elevated. Taken together, these data demonstrate in vivo that the hepatic energy state is sensitive to glucagon receptor activation and requires PEPCK-C, thus providing new insights into liver metabolism. IntroductionThe energy state in the cell is defined by adenine nucleotide levels and is critically coupled to nearly all metabolic processes (1). In the cell, the adenine nucleotides ATP, ADP, and AMP are tied directly or indirectly to all energetic pathways and allosterically control numerous regulatory enzymes (2-6). Changes in adenine nucleotides typically occur such that ATP and AMP deviate in reciprocal directions, while ADP remains constant (1). Such changes are the basis for using the ratio AMP/ATP (1, 7) or the equation for cellular energy charge ([ATP + (0.5 × ADP)] / [ATP + ADP + AMP]) (8, 9) as indices of the metabolic environment. Metabolic stress is thus characterized by a rise in AMP paired with a fall in ATP levels, reflecting a decrease in energy state. A fall in energy state is of considerable importance, in part due to the regulatory role of AMP/ATP ratios on AMPK activity (10). AMPK is a metabolic switch sensitive to high AMP/ATP ratios and functions to protect the energy state by inhibiting ATP-consuming processes while stimulating ATP-producing processes. (10).In most tissues, the environment is controlled to maintain a high energy state (low AMP/ATP ratio). In skeletal muscle, for example, creatine kinase limits reductions in ATP during conditions such as exercise, when energy utilization is accelerated (11,12). The liver, in contrast, lacks creatine kinase, and exercise has been shown to markedly decrease the hepatic energy state and increase the phosphorylation of AMPK (11, 13). The regulatory...

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Section: Figurementioning

confidence: 99%

Section: Figurementioning

confidence: 99%

Section: Figurementioning

confidence: 99%

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Hepatic energy state is regulated by glucagon receptor signaling in mice

et al. 2009

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“…It has been reported to be increased after exercise in urine of animals and humans as an effect of oxidative metabolism of adenine nucleotides. Allantoin excretion is increased by physical exercise in human blood [23,24]. The murine models are able to produce this catabolite, while in human urine, this catabolite has been investigated in relation with other markers of oxidative stress [24].…”

Section: Discussionmentioning

confidence: 99%

NMR metabolomics for assessment of exercise effects with mouse biofluids

et al. 2012

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Exercise modulates the metabolome in urine or blood as demonstrated previously for humans and animal models. Using nuclear magnetic resonance (NMR) metabolomics, the present study compares the metabolic consequences of an exhaustive exercise at peak velocity (Vp) and at critical velocity (Vc) on mice. Since small-volume samples (blood and urine) were collected, dilution was necessary to acquire NMR spectra. Consequently, specific processing methods were applied before statistical analysis. According to the type of exercise (control group, Vp group and Vc group), 26 male mice were divided into three groups. Mice were sacrificed 2 h after the end of exercise, and urine and blood samples were drawn from each mouse. Proton NMR spectra were acquired with urine and deproteinized blood. The NMR data were aligned with the icoshift method and normalised using the probabilistic quotient method. Finally, data were analysed with the orthogonal projection of latent-structure analysis. The spectra obtained with deproteinized blood can neither discriminate the control mice from exercised mice nor discriminate according to the duration of the exercise. With urine samples, a significant statistical model can be estimated when comparing the control mice to both groups, Vc and Vp. The best model is obtained according to the exercise duration with all mice. Taking into account the spectral regions having the highest correlations, the discriminant metabolites are allantoin, inosine and branched-chain amino acids. In conclusion, metabolomic profiles assessed with NMR are highly dependent on the exercise. These results show that urine samples are more informative than blood samples and that the duration of the exercise is a more important parameter to influence the metabolomic status than the exercise velocity.

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“…However, it is interesting to point out that levels and synthesis of adenine nucleotides in the liver are frequently associated to exercise. Actually, intense exercise usually leads to degradation of adenine mononucleotides in tissues like muscle and liver . A recovery by the novo synthesis takes place after the intense exercises .…”

Section: Discussionmentioning

confidence: 99%

Actions of p‐synephrine on hepatic enzyme activities linked to carbohydrate metabolism and ATP levels in vivo and in the perfused rat liver

Maldonado

Bracht

Sá‐Nakanishi

et al. 2017

Cell Biochemistry & Function

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p-Synephrine is one of the main active components of the fruit of Citrus aurantium (bitter orange).Extracts of the bitter orange and other preparations containing p-synephrine have been used worldwide to promote weight loss and for sports performance. The purpose of the study was to measure the action of p-synephrine on hepatic enzyme activities linked to carbohydrate and energy metabolism and the levels of adenine mononucleotides. Enzymes and adenine mononucleotides were measured in the isolated perfused rat liver and in vivo after oral administration of the drug (50 and 300 mg/kg) by using standard techniques. p-Synephrine increased the activity of glycogen phosphorylase in vivo and in the perfused liver. It decreased, however, the activities of pyruvate kinase and pyruvate dehydrogenase also in vivo and in the perfused liver.p-Synephrine increased the hepatic pools of adenosine diphosphate and adenosine triphosphate.Stimulation of glycogen phosphorylase is consistent with the reported increased glycogenolysis in the perfused liver and increased glycemia in rats. The decrease in the pyruvate dehydrogenase activity indicates that p-synephrine is potentially capable of inhibiting the transformation of carbohydrates into lipids. The capability of increasing the adenosine triphosphate-adenosine diphosphate pool indicates a beneficial effect of p-synephrine on the cellular energetics. KEYWORDS liver metabolism, metabolic effectors, natural protoalkaloids, sport performance, weight loss effect

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Intense exercise induces the degradation of adenine nucleotide and purine nucleotide synthesis via de novo pathway in the rat liver

Cited by 8 publications

References 30 publications

Hepatic energy state is regulated by glucagon receptor signaling in mice

Hepatic energy state is regulated by glucagon receptor signaling in mice

NMR metabolomics for assessment of exercise effects with mouse biofluids

Actions of p‐synephrine on hepatic enzyme activities linked to carbohydrate metabolism and ATP levels in vivo and in the perfused rat liver

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