Energy state of the liver during short-term and exhaustive exercise in C57BL/6J mice

Camacho, Raul C.; Donahue, E. Patrick; James, Freyja D.; Berglund, Eric D.; Wasserman, David H.

doi:10.1152/ajpendo.00385.2005

Cited by 60 publications

(65 citation statements)

References 35 publications

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“…3A). The AMP/ATP ratio and EC were similar to previous measurements taken under postabsorptive conditions (11). The AICAR infusion resulted in a significant reduction in the total adenine nucleotide pool (3.3 Ϯ 0.09 to 1.6 Ϯ 0.02 mol⅐g (Fig.…”

supporting

confidence: 86%

5-Aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR) Effect on Glucose Production, but Not Energy Metabolism, Is Independent of Hepatic AMPK in Vivo

Hasenour

Ridley

Hughey

et al. 2014

Journal of Biological Chemistry

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Background: AMPK is implicated as the mediator of AICAR action on liver metabolism. Results: AICAR suppresses glucose production independent of AMPK. Regulation of mitochondrial function is AMPK-dependent. Conclusion: Nucleotide monophosphates rely on AMPK to regulate energy metabolism but not to suppress glucose production. Significance: Targeted AMPK activation will not lower glucose production in metabolic diseases but could improve hepatic energetics.

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supporting

confidence: 86%

5-Aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR) Effect on Glucose Production, but Not Energy Metabolism, Is Independent of Hepatic AMPK in Vivo

Hasenour

Ridley

Hughey

et al. 2014

Journal of Biological Chemistry

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“…Notably, the working intensity settings in this study (14 m/min, 0% grade, 60 min) were very low in comparison to the maximal endurance capacity of wild-type mice. At a speed of 20 m/min and 5% inclination, C57Bl6 mice become exhausted after approximately 85 min ( 21 ). Yet, under the low intensity conditions applied in this study that did not affect liver glycogen levels in wild-type animals, liver glycogen stores in ATGL-ko and ATGL-ko/CM mice were almost depleted.…”

Section: Discussionmentioning

confidence: 57%

Adipose triglyceride lipase plays a key role in the supply of the working muscle with fatty acids

Schoiswohl

Schweiger

Schreiber

et al. 2010

Journal of Lipid Research

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This article is available online at http://www.jlr.orgCarbohydrates and FAs are the major energy substrates in the working muscle. The use of FAs for energy conversion depends, among other things, on exercise intensity and duration. During prolonged exercise, when carbohydrate reserves get depleted, oxidation of FAs becomes increasingly important ( 1, 2 ). Under these conditions, FAs are imported from plasma sources or mobilized from intramyocellular stores. Most of the body's energy reserves are stored in white adipose tissue (WAT) implicating that the supply of the muscle with energy during prolonged exercise is largely dependent on adipose lipolysis. The mobilization of FAs in adipose tissue is tightly controlled by hormones. Catecholamines and other effectors activate lip ases resulting in increased FA release into the circulation ( 3, 4 ). Adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) are the major triglyceride (TG) lipases in this process. HSL most effi ciently hydrolyses diglycerides (DGs), but is also capable of degrading several other lipid substrates including TGs, monoglycerides, cholesteryl ester, and retinyl ester ( 5 ). In HSL-deficient WAT, TG hydrolysis results in the accumulation of DG, suggesting that HSL is a major DG hydrolase in vivo ( 6 ). ATGL specifi cally performs the fi rst step in lipolysis, generating DGs and FAs ( 7 ). ATGL-defi ciency in mice results in obesity caused by severely reduced TG hydrolysis in adipose tissue. Increased deposition of TG is also observed in many other tissues ( 8 ). In the absence of both enzymes, hormone-induced FA release in WAT is decreased by more than 95% ( 9 ). Together, these observations suggest that effi cient lipolysis is dependent on the coordinate action of Abstract FAs are mobilized from triglyceride (TG) stores during exercise to supply the working muscle with energy. Mice defi cient for adipose triglyceride lipase (ATGL-ko) exhi bit defective lipolysis and accumulate TG in adipose tissue and muscle, suggesting that ATGL defi ciency affects energy availability and substrate utilization in working muscle. In this study, we investigated the effect of moderate treadmill exercise on blood energy metabolites and liver glycogen stores in mice lacking ATGL. Because ATGL-ko mice exhibit massive accumulation of TG in the heart and cardiomyopathy, we also investigated a mouse model lacking ATGL in all tissues except cardiac muscle (ATGL-ko/CM). In contrast to ATGL-ko mice, these mice did not accumulate TG in the heart and had normal life expectancy. Exercise experiments revealed that ATGL-ko and ATGL-ko/CM mice are unable to increase circulating FA levels during exercise. The reduced availability of FA for energy conversion led to rapid depletion of liver glycogen stores and hypoglycemia. Together, our studies suggest that ATGL-ko mice cannot adjust circulating FA levels to the increased energy requirements of the working muscle, resulting in an increased use of carbohydrates for energy conversion. Thus, ATGL activity is required...

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“…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).…”

Section: Introductionmentioning

confidence: 99%

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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Energy state of the liver during short-term and exhaustive exercise in C57BL/6J mice

Cited by 60 publications

References 35 publications

5-Aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR) Effect on Glucose Production, but Not Energy Metabolism, Is Independent of Hepatic AMPK in Vivo

5-Aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR) Effect on Glucose Production, but Not Energy Metabolism, Is Independent of Hepatic AMPK in Vivo

Adipose triglyceride lipase plays a key role in the supply of the working muscle with fatty acids

Hepatic energy state is regulated by glucagon receptor signaling in mice

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