scholarly journals Lymphocytes Mitochondrial Physiology as Biomarker of Energy Metabolism during Fasted and Fed Conditions

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Erika Cortez ◽  
Fabiana A. Neves ◽  
Amélia F. Bernardo ◽  
Ana Carolina Stumbo ◽  
Laís Carvalho ◽  
...  
Keyword(s):  
Energy Metabolism ◽  
Metabolic Disorders ◽  
Glucose Transporters ◽  
Cell Types ◽  
Acid Oxidation ◽  
Uncouple Protein ◽  
Main Hypothesis ◽  
Energy Dynamics ◽  
Amp Activated Protein Kinase ◽  
Different Cell Types

Mitochondria are central coordinators of energy metabolism, and changes of their physiology have long been associated with metabolic disorders. Thus, observations of energy dynamics in different cell types are of utmost importance. Therefore, tools with quick and easy handling are needed for consistent evaluations of such interventions. In this paper, our main hypothesis is that during different nutritional situations lymphocytes mitochondrial physiology could be associated with the metabolism of other cell types, such as cardiomyocytes, and consequently be used as metabolic biomarker. Blood lymphocytes and heart muscle fibers were obtained from both fed and 24 h-fasted mice, and mitochondrial analysis was assessed by high-resolution respirometry and western blotting. Carbohydrate-linked oxidation and fatty acid oxidation were significantly higher after fasting. Carnitine palmitoil transferase 1 and uncouple protein 2 contents were increased in the fasted group, while the glucose transporters 1 and 4 and the ratio phosphorylated AMP-activated protein kinase/AMPK did not change between groups. In summary, under a nutritional status modification, mitochondria demonstrated earlier adaptive capacity than other metabolic sensors such as glucose transporters and AMPK, suggesting the accuracy of mitochondria physiology of lymphocytes as biomarker for metabolic changes.

scholarly journals AMPK as a mediator of hormonal signalling

2009 ◽  
Vol 44 (2) ◽  
pp. 87-97 ◽  
Author(s):  
Chung Thong Lim ◽  
Blerina Kola ◽  
Márta Korbonits
Keyword(s):  
Protein Synthesis ◽  
Fatty Acid ◽  
Metabolic Disorders ◽  
Energy Homeostasis ◽  
Metabolic Effects ◽  
Whole Body ◽  
Acid Oxidation ◽  
Treatment Of Obesity ◽  
Amp Activated Protein Kinase ◽  
Hormonal Signalling

AMP-activated protein kinase (AMPK) is a key molecular player in energy homeostasis at both cellular and whole-body levels. AMPK has been shown to mediate the metabolic effects of hormones such as leptin, ghrelin, adiponectin, glucocorticoids and insulin as well as cannabinoids. Generally, activated AMPK stimulates catabolic pathways (glycolysis, fatty acid oxidation and mitochondrial biogenesis) and inhibits anabolic pathways (gluconeogenesis, glycogen, fatty acid and protein synthesis), and has a direct appetite-regulating effect in the hypothalamus. Drugs that activate AMPK, namely metformin and thiazolidinediones, are often used to treat metabolic disorders. Thus, AMPK is now recognised as a potential target for the treatment of obesity and associated co-morbidities.

3,5-Diiodo-l-thyronine rapidly enhances mitochondrial fatty acid oxidation rate and thermogenesis in rat skeletal muscle: AMP-activated protein kinase involvement

2009 ◽  
Vol 296 (3) ◽  
pp. E497-E502 ◽  
Author(s):  
A. Lombardi ◽  
P. de Lange ◽  
E. Silvestri ◽  
R. A. Busiello ◽  
A. Lanni ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acids ◽  
Fatty Acid ◽  
Energy Metabolism ◽  
Fatty Acid Oxidation ◽  
Atp Synthesis ◽  
Acid Oxidation ◽  
Mitochondrial Fatty Acid Oxidation ◽  
Mitochondrial Fatty Acid ◽  
Amp Activated Protein Kinase

Triiodothyronine regulates energy metabolism and thermogenesis. Among triiodothyronine derivatives, 3,5-diiodo-l-thyronine (T2) has been shown to exert marked effects on energy metabolism by acting mainly at the mitochondrial level. Here we investigated the capacity of T2 to affect both skeletal muscle mitochondrial substrate oxidation and thermogenesis within 1 h after its injection into hypothyroid rats. Administration of T2 induced an increase in mitochondrial oxidation when palmitoyl-CoA (+104%), palmitoylcarnitine (+80%), or succinate (+30%) was used as substrate, but it had no effect when pyruvate was used. T2 was able to 1) activate the AMPK-ACC-malonyl-CoA metabolic signaling pathway known to direct lipid partitioning toward oxidation and 2) increase the importing of fatty acids into the mitochondrion. These results suggest that T2 stimulates mitochondrial fatty acid oxidation by activating several metabolic pathways, such as the fatty acid import/β-oxidation cycle/FADH2-linked respiratory pathways, where fatty acids are imported. T2 also enhanced skeletal muscle mitochondrial thermogenesis by activating pathways involved in the dissipation of the proton-motive force not associated with ATP synthesis (“proton leak”), the effect being dependent on the presence of free fatty acids inside mitochondria. We conclude that skeletal muscle is a target for T2, and we propose that, by activating processes able to enhance mitochondrial fatty acid oxidation and thermogenesis, T2 could play a role in protecting skeletal muscle against excessive intramyocellular lipid storage, possibly allowing it to avoid functional disorders.

scholarly journals Benzimidazole derivative small-molecule 991 enhances AMPK activity and glucose uptake induced by AICAR or contraction in skeletal muscle

2016 ◽  
Vol 311 (4) ◽  
pp. E706-E719 ◽  
Author(s):  
Laurent Bultot ◽  
Thomas E. Jensen ◽  
Yu-Chiang Lai ◽  
Agnete L. B. Madsen ◽  
Caterina Collodet ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Glucose Transport ◽  
Energy Homeostasis ◽  
Ex Vivo ◽  
Benzimidazole Derivative ◽  
Cell Types ◽  
Α Subunit ◽  
Ampk Activity ◽  
Amp Activated Protein Kinase ◽  
Different Cell Types

AMP-activated protein kinase (AMPK) plays diverse roles and coordinates complex metabolic pathways for maintenance of energy homeostasis. This could be explained by the fact that AMPK exists as multiple heterotrimer complexes comprising a catalytic α-subunit (α1 and α2) and regulatory β (β1 and β2)- and γ (γ1, γ2, γ3)-subunits, which are uniquely distributed across different cell types. There has been keen interest in developing specific and isoform-selective AMPK-activating drugs for therapeutic use and also as research tools. Moreover, establishing ways of enhancing cellular AMPK activity would be beneficial for both purposes. Here, we investigated if a recently described potent AMPK activator called 991, in combination with the commonly used activator 5-aminoimidazole-4-carboxamide riboside or contraction, further enhances AMPK activity and glucose transport in mouse skeletal muscle ex vivo. Given that the γ3-subunit is exclusively expressed in skeletal muscle and has been implicated in contraction-induced glucose transport, we measured the activity of AMPKγ3 as well as ubiquitously expressed γ1-containing complexes. We initially validated the specificity of the antibodies for the assessment of isoform-specific AMPK activity using AMPK-deficient mouse models. We observed that a low dose of 991 (5 μM) stimulated a modest or negligible activity of both γ1- and γ3-containing AMPK complexes. Strikingly, dual treatment with 991 and 5-aminoimidazole-4-carboxamide riboside or 991 and contraction profoundly enhanced AMPKγ1/γ3 complex activation and glucose transport compared with any of the single treatments. The study demonstrates the utility of a dual activator approach to achieve a greater activation of AMPK and downstream physiological responses in various cell types, including skeletal muscle.

scholarly journals ATP increases within the lumen of the endoplasmic reticulum upon intracellular Ca2+release

2014 ◽  
Vol 25 (3) ◽  
pp. 368-379 ◽  
Author(s):  
Neelanjan Vishnu ◽  
Muhammad Jadoon Khan ◽  
Felix Karsten ◽  
Lukas N. Groschner ◽  
Markus Waldeck-Weiermair ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Single Cells ◽  
Cell Types ◽  
Additional Energy ◽  
Intracellular Ca ◽  
A Cell ◽  
Specific Regulation ◽  
Amp Activated Protein Kinase ◽  
Different Cell Types

Multiple functions of the endoplasmic reticulum (ER) essentially depend on ATP within this organelle. However, little is known about ER ATP dynamics and the regulation of ER ATP import. Here we describe real-time recordings of ER ATP fluxes in single cells using an ER-targeted, genetically encoded ATP sensor. In vitro experiments prove that the ATP sensor is both Ca2+and redox insensitive, which makes it possible to monitor Ca2+-coupled ER ATP dynamics specifically. The approach uncovers a cell type–specific regulation of ER ATP homeostasis in different cell types. Moreover, we show that intracellular Ca2+release is coupled to an increase of ATP within the ER. The Ca2+-coupled ER ATP increase is independent of the mode of Ca2+mobilization and controlled by the rate of ATP biosynthesis. Furthermore, the energy stress sensor, AMP-activated protein kinase, is essential for the ATP increase that occurs in response to Ca2+depletion of the organelle. Our data highlight a novel Ca2+-controlled process that supplies the ER with additional energy upon cell stimulation.

Role of AMP-activated protein kinase in healthy and diseased hearts

2006 ◽  
Vol 291 (6) ◽  
pp. H2557-H2569 ◽  
Author(s):  
Vernon W. Dolinsky ◽  
Jason R. B. Dyck
Keyword(s):  
Energy Metabolism ◽  
Protein Kinase ◽  
Cardiac Myocyte ◽  
Acid Oxidation ◽  
Ampk Activation ◽  
Cardiac Energy Metabolism ◽  
Ampk Activity ◽  
Cardiac Energy ◽  
Metabolic Stresses ◽  
Amp Activated Protein Kinase

The heart is capable of utilizing a variety of substrates to produce the necessary ATP for cardiac function. AMP-activated protein kinase (AMPK) has emerged as a key regulator of cellular energy homeostasis and coordinates multiple catabolic and anabolic pathways in the heart. During times of acute metabolic stresses, cardiac AMPK activation seems to be primarily involved in increasing energy-generating pathways to maintain or restore intracellular ATP levels. In acute situations such as mild ischemia or short durations of severe ischemia, activation of cardiac AMPK appears to be necessary for cardiac myocyte function and survival by stimulating ATP generation via increased glycolysis and accelerated fatty acid oxidation. Whereas AMPK activation may be essential for adaptation of cardiac energy metabolism to acute and/or minor metabolic stresses, it is unknown whether AMPK activation becomes maladaptive in certain chronic disease states and/or extreme energetic stresses. However, alterations in cardiac AMPK activity are associated with a number of cardiovascular-related diseases such as pathological cardiac hypertrophy, myocardial ischemia, glycogen storage cardiomyopathy, and Wolff-Parkinson-White syndrome, suggesting the possibility of a maladaptive role. Although the precise role AMPK plays in the diseased heart is still in question, it is clear that AMPK is a major regulator of cardiac energy metabolism. The consequences of alterations in AMPK activity and subsequent cardiac energy metabolism in the healthy and the diseased heart will be discussed.

Energy metabolism at the cellular level of the CNS

1992 ◽  
Vol 70 (S1) ◽  
pp. S145-S157 ◽  
Author(s):  
Leif Hertz ◽  
Liang Peng
Keyword(s):  
Energy Metabolism ◽  
Brain Slices ◽  
Cell Types ◽  
Cellular Level ◽  
Extracellular Potassium ◽  
High Potassium ◽  
Cultured Astrocytes ◽  
Preferential Uptake ◽  
Different Cell Types

Evidence is accumulating that interactions between different cell types are of paramount importance for CNS function, for example, release of the excitatory transmitter glutamate from neurons and its preferential uptake into astrocytes. Some information is also available about energy metabolism in different cell types, or more often in models of different cell types (e.g., synaptosomes, cultured neurons, cultured astrocytes). In this review an attempt is made not only to correlate information obtained with different cell models but also to integrate this information with in vivo data, with histochemical observations, and with results obtained using brain slices. The emerging patterns indicate that neurons, synaptosomes, and astrocytes are all capable of complete glycolysis and oxidation of glucose. Elevated extracellular concentrations of potassium, known to occur in vivo, enhance energy metabolism by mechanisms that differ between neurons and astrocytes and to a large extent serve to reaccumulate extracellular potassium ions into adjacent cells. Monoaminergic agonists also stimulate energy metabolism, but mainly or exclusively in astrocytes. Profound differences are found between the effects of excess potassium and of aminergic transmitters, suggesting that high potassium concentrations enhance neuronal–astrocytic interactions, whereas the monoamines may tend to dissociate metabolic events in neurons and in astrocytes.Key words: astrocytes, neurons, synaptosomes, potassium, noradrenaline.

scholarly journals Glucose transporters in the uterus: an analysis of tissue distribution and proposed physiological roles

Reproduction ◽  
2011 ◽  
Vol 142 (2) ◽  
pp. 211-220 ◽  
Author(s):  
Antonina I Frolova ◽  
Kelle H Moley
Keyword(s):  
Glucose Transport ◽  
Current Knowledge ◽  
Embryo Implantation ◽  
Glucose Transporters ◽  
Cell Types ◽  
Uterine Endometrium ◽  
Different Cell Types ◽  
Transport Molecules ◽  
Ovarian Syndrome

Facilitative glucose transport molecules (glucose transporters, GLUTs) are responsible for glucose transport across cellular membranes. Of the 14 family members, expression of nine has been reported in the murine uterus and seven in the human uterus. Some studies reveal that adequate glucose uptake and metabolism are essential for the proper differentiation of the uterine endometrium toward a receptive state capable of supporting embryo implantation. However, the mechanistic role of GLUTs in endometrial function remains poorly understood. This review aims to present the current knowledge about GLUT expression in the uterus and distribution among the different cell types within the endometrium. In addition, it analyzes the available data in the context of roles GLUTs may play in normal uterine physiology as well as the pathological conditions of infertility, endometrial cancer, and polycystic ovarian syndrome.

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