scholarly journals Hypothalamic AMPK as a Regulator of Energy Homeostasis

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
My Khanh Q. Huynh ◽  
Ann W. Kinyua ◽  
Dong Joo Yang ◽  
Ki Woo Kim
Keyword(s):  
Energy Balance ◽  
Energy Homeostasis ◽  
Energy State ◽  
Glucose Production ◽  
Energy Output ◽  
Energy Sensor ◽  
Increase Energy Intake ◽  
Ampk Activity ◽  
Underlying Mechanisms ◽  
Amp Activated Protein Kinase

Activated in energy depletion conditions, AMP-activated protein kinase (AMPK) acts as a cellular energy sensor and regulator in both central nervous system and peripheral organs. Hypothalamic AMPK restores energy balance by promoting feeding behavior to increase energy intake, increasing glucose production, and reducing thermogenesis to decrease energy output. Besides energy state, many hormones have been shown to act in concert with AMPK to mediate their anorexigenic and orexigenic central effects as well as thermogenic influences. Here we explore the factors that affect hypothalamic AMPK activity and give the underlying mechanisms for the role of central AMPK in energy homeostasis together with the physiological effects of hypothalamic AMPK on energy balance restoration.

scholarly journals Glucose regulates AMP-activated protein kinase activity and gene expression in clonal, hypothalamic neurons expressing proopiomelanocortin: additive effects of leptin or insulin

2007 ◽  
Vol 192 (3) ◽  
pp. 605-614 ◽  
Author(s):  
Fang Cai ◽  
Armen V Gyulkhandanyan ◽  
Michael B Wheeler ◽  
Denise D Belsham
Keyword(s):  
Protein Kinase ◽  
Energy Homeostasis ◽  
Cell Model ◽  
Neuronal Cell ◽  
Cell Types ◽  
Glucose Sensing ◽  
Protein Kinase Activity ◽  
Energy Status ◽  
Ampk Activity ◽  
Amp Activated Protein Kinase

The mammalian hypothalamus comprises an array of phenotypically distinct cell types that interpret peripheral signals of energy status and, in turn, elicits an appropriate response to maintain energy homeostasis. We used a clonal representative hypothalamic cell model expressing proopiomelanocortin (POMC; N-43/5) to study changes in AMP-activated protein kinase (AMPK) activity and glucose responsiveness. We have demonstrated the presence of cellular machinery responsible for glucose sensing in the cell line, including glucokinase, glucose transporters, and appropriate ion channels. ATP-sensitive potassium channels were functional and responded to glucose. The N-43/5 POMC neurons may therefore be an appropriate cell model to study glucose-sensing mechanisms in the hypothalamus. In N-43/5 POMC neurons, increasing glucose concentrations decreased phospho-AMPK activity. As a relevant downstream effect, we found that POMC transcription increased with 2.8 and 16.7 mM glucose. Upon addition of leptin, with either no glucose or with 5 mM glucose, we found that leptin decreased AMPK activity in N-43/5 POMC neurons, but had no significant effect at 25 mM glucose, whereas insulin decreased AMPK activity at only 5 mM glucose. These results demonstrate that individual hypothalamic neuronal cell types, such as the POMC neuron, can have distinct responses to peripheral signals that relay energy status to the brain, and will therefore be activated uniquely to control neuroendocrine function.

scholarly journals Broken Energy Homeostasis and Obesity Pathogenesis: The Surrounding Concepts

2018 ◽  
Vol 7 (11) ◽  
pp. 453 ◽  
Author(s):  
Abdelaziz Ghanemi ◽  
Mayumi Yoshioka ◽  
Jonny St-Amand
Keyword(s):  
Energy Balance ◽  
Population Health ◽  
Clinical Evaluation ◽  
Health Problem ◽  
Psychological Factors ◽  
Energy Homeostasis ◽  
Fat Accumulation ◽  
Underlying Mechanisms ◽  
Diagnosis Classification

Obesity represents an abnormal fat accumulation resulting from energy imbalances. It represents a disease with heavy consequences on population health and society economy due to its related morbidities and epidemic proportion. Defining and classifying obesity and its related parameters of evaluation is the first challenge toward understanding this multifactorial health problem. Therefore, within this review we report selected illustrative examples of the underlying mechanisms beyond the obesity pathogenesis which is systemic rather than limited to fat accumulation. We also discuss the gut-brain axis and hormones as the controllers of energy homeostasis and report selected impacts of obesity on the key metabolic tissues. The concepts of “broken energy balance” is detailed as the obesity starting key step. Sleep shortage and psychological factors are also reported with influences on obesity development. Importantly, describing such mechanistic pathways would allow clinicians, biologists and researchers to develop and optimize approaches and methods in terms of diagnosis, classification, clinical evaluation, treatment and prognosis of obesity.

scholarly journals Hypothalamic AMPK as a Mediator of Hormonal Regulation of Energy Balance

2018 ◽  
Vol 19 (11) ◽  
pp. 3552 ◽  
Author(s):  
Baile Wang ◽  
Kenneth Cheng
Keyword(s):  
Energy Balance ◽  
Hormonal Regulation ◽  
Energy Homeostasis ◽  
Adenosine Monophosphate ◽  
Acid Oxidation ◽  
Peripheral Tissues ◽  
Adaptive Thermogenesis ◽  
Increase Food Intake ◽  
Regulatory Effects ◽  
Underlying Mechanisms

As a cellular energy sensor and regulator, adenosine monophosphate (AMP)-activated protein kinase (AMPK) plays a pivotal role in the regulation of energy homeostasis in both the central nervous system (CNS) and peripheral organs. Activation of hypothalamic AMPK maintains energy balance by inducing appetite to increase food intake and diminishing adaptive thermogenesis in adipose tissues to reduce energy expenditure in response to food deprivation. Numerous metabolic hormones, such as leptin, adiponectin, ghrelin and insulin, exert their energy regulatory effects through hypothalamic AMPK via integration with the neural circuits. Although activation of AMPK in peripheral tissues is able to promote fatty acid oxidation and insulin sensitivity, its chronic activation in the hypothalamus causes obesity by inducing hyperphagia in both humans and rodents. In this review, we discuss the role of hypothalamic AMPK in mediating hormonal regulation of feeding and adaptive thermogenesis, and summarize the diverse underlying mechanisms by which central AMPK maintains energy homeostasis.

scholarly journals AMP-activated protein kinase pathway and bone metabolism

2011 ◽  
Vol 212 (3) ◽  
pp. 277-290 ◽  
Author(s):  
J Jeyabalan ◽  
M Shah ◽  
B Viollet ◽  
C Chenu
Keyword(s):  
Protein Kinase ◽  
Energy Homeostasis ◽  
Bone Cells ◽  
Peripheral Tissues ◽  
Ampk Signaling ◽  
Obesity And Diabetes ◽  
Regulate Food Intake ◽  
Ampk Activity ◽  
Amp Activated Protein Kinase

There is increasing evidence that osteoporosis, similarly to obesity and diabetes, could be another disorder of energy metabolism. AMP-activated protein kinase (AMPK) has emerged over the last decade as a key sensing mechanism in the regulation of cellular energy homeostasis and is an essential mediator of the central and peripheral effects of many hormones on the metabolism of appetite, fat and glucose. Novel work demonstrates that the AMPK signaling pathway also plays a role in bone physiology. Activation of AMPK promotes bone formationin vitroand the deletion of α or β subunit of AMPK decreases bone mass in mice. Furthermore, AMPK activity in bone cells is regulated by the same hormones that regulate food intake and energy expenditure through AMPK activation in the brain and peripheral tissues. AMPK is also activated by antidiabetic drugs such as metformin and thiazolidinediones (TZDs), which also impact on skeletal metabolism. Interestingly, TZDs have detrimental skeletal side effects, causing bone loss and increasing the risk of fractures, although the role of AMPK mediation is still unclear. These data are presented in this review that also discusses the potential roles of AMPK in bone as well as the possibility for AMPK to be a future therapeutic target for intervention in osteoporosis.

scholarly journals Dissecting the Role of 5′-AMP for Allosteric Stimulation, Activation, and Deactivation of AMP-activated Protein Kinase

2006 ◽  
Vol 281 (43) ◽  
pp. 32207-32216 ◽  
Author(s):  
Marianne Suter ◽  
Uwe Riek ◽  
Roland Tuerk ◽  
Uwe Schlattner ◽  
Theo Wallimann ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Phosphatase ◽  
Energy Homeostasis ◽  
Adenine Nucleotides ◽  
Enzyme Preparations ◽  
Activity Measurements ◽  
Ampk Activity ◽  
Amp Activated Protein Kinase

AMP-activated protein kinase (AMPK) is a heterotrimeric protein kinase that is crucial for cellular energy homeostasis of eukaryotic cells and organisms. Here we report on the activation of AMPK α1β1γ1 and α2β2γ1 by their upstream kinases (Ca2+/calmodulin-dependent protein kinase kinase-β and LKB1-MO25α-STRADα), the deactivation by protein phosphatase 2Cα, and on the extent of stimulation of AMPK by its allosteric activator AMP, using purified recombinant enzyme preparations. An accurate high pressure liquid chromatography-based method for AMPK activity measurements was established, which allowed for direct quantitation of the unphosphorylated and phosphorylated artificial peptide substrate, as well as the adenine nucleotides. Our results show a 1000-fold activation of AMPK by the combined effects of upstream kinase and saturating concentrations of AMP. The two AMPK isoforms exhibit similar specific activities (6 μmol/min/mg) and do not differ significantly by their responsiveness to AMP. Due to the inherent instability of ATP and ADP, it proved impossible to assay AMPK activity in the absolute absence of AMP. However, the half-maximal stimulatory effect of AMP is reached below 2 μm. AMP does not appear to augment phosphorylation by upstream kinases in the purified in vitro system, but deactivation by dephosphorylation of AMPK α-subunits at Thr-172 by protein phosphatase 2Cα is attenuated by AMP. Furthermore, it is shown that neither purified NAD+ nor NADH alters the activity of AMPK in a concentration range of 0–300 μm, respectively. Finally, evidence is provided that ZMP, a compound formed in 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside-treated cells to activate AMPK in vivo, allosterically activates purified AMPK in vitro, but compared with AMP, maximal activity is not reached. These data shed new light on physiologically important aspects of AMPK regulation.

AMP-activated protein kinase and the regulation of glucose transport

2006 ◽  
Vol 291 (5) ◽  
pp. E867-E877 ◽  
Author(s):  
Nobuharu Fujii ◽  
Niels Jessen ◽  
Laurie J. Goodyear
Keyword(s):  
Skeletal Muscle ◽  
Protein Kinase ◽  
Cardiac Muscle ◽  
Glucose Transport ◽  
Whole Body ◽  
Insulin Resistant ◽  
Treatment And Prevention ◽  
Ampk Activity ◽  
Underlying Mechanisms ◽  
Amp Activated Protein Kinase

The AMP-activated protein kinase (AMPK) is an energy-sensing enzyme that is activated by acute increases in the cellular [AMP]/[ATP] ratio. In skeletal and/or cardiac muscle, AMPK activity is increased by stimuli such as exercise, hypoxia, ischemia, and osmotic stress. There are many lines of evidence that increasing AMPK activity in skeletal muscle results in increased rates of glucose transport. Although similar to the effects of insulin to increase glucose transport in muscle, it is clear that the underlying mechanisms for AMPK-mediated glucose transport involve proximal signals that are distinct from that of insulin. Here, we discuss the evidence for AMPK regulation of glucose transport in skeletal and cardiac muscle and describe research investigating putative signaling mechanisms mediating this effect. We also discuss evidence that AMPK may play a role in enhancing muscle and whole body insulin sensitivity for glucose transport under conditions such as exercise, as well as the use of the AMPK activator AICAR to reverse insulin-resistant conditions. The identification of AMPK as a novel glucose transport mediator in skeletal muscle is providing important insights for the treatment and prevention of type 2 diabetes.

scholarly journals Roles of 5′-AMP-activated protein kinase (AMPK) in mammalian glucose homoeostasis

2003 ◽  
Vol 375 (1) ◽  
pp. 1-16 ◽  
Author(s):  
Guy A. RUTTER ◽  
Gabriela da SILVA XAVIER ◽  
Isabelle LECLERC
Keyword(s):  
Protein Kinase ◽  
Glucose Production ◽  
Nutrient Sensing ◽  
Energy Status ◽  
Β Cells ◽  
Glucose Homoeostasis ◽  
New Findings ◽  
Ampk Activity ◽  
Amp Activated Protein Kinase ◽  
The Brain

AMPK (5′-AMP-activated protein kinase) is emerging as a metabolic master switch, by which cells in both mammals and lower organisms sense and decode changes in energy status. Changes in AMPK activity have been shown to regulate glucose transport in muscle and glucose production by the liver. Moreover, AMPK appears to be a key regulator of at least one transcription factor linked to a monogenic form of diabetes mellitus. As a result, considerable efforts are now under way to explore the usefulness of AMPK as a therapeutic target for other forms of this disease. Here we review this topic, and discuss new findings which suggest that AMPK may play roles in regulating insulin release and the survival of pancreatic islet β-cells, and nutrient sensing by the brain.

AMP kinase (PRKAA1)

2014 ◽  
Vol 67 (9) ◽  
pp. 758-763 ◽  
Author(s):  
Sukriti Krishan ◽  
Des R Richardson ◽  
Sumit Sahni
Keyword(s):  
Energy Homeostasis ◽  
Atp Synthesis ◽  
Cellular Growth ◽  
Α Subunit ◽  
Cellular Energy ◽  
Therapeutic Drugs ◽  
Energy Sensor ◽  
Energy Consuming ◽  
Cardiac Disorders ◽  
Amp Activated Protein Kinase

The PRKAA1 gene encodes the catalytic α-subunit of 5′ AMP-activated protein kinase (AMPK). AMPK is a cellular energy sensor that maintains energy homeostasis within the cell and is activated when the AMP/ATP ratio increases. When activated, AMPK increases catabolic processes that increase ATP synthesis and inhibit anabolic processes that require ATP. Additionally, AMPK also plays a role in activating autophagy and inhibiting energy consuming processes, such as cellular growth and proliferation. Due to its role in energy metabolism, it could act as a potential target of many therapeutic drugs that could be useful in the treatment of several diseases, for example, diabetes. Moreover, AMPK has been shown to be involved in inhibiting tumour growth and metastasis, and has also been implicated in the pathology of neurodegenerative and cardiac disorders. Hence, a better understanding of AMPK and its role in various pathological conditions could enable the development of strategies to use it as a therapeutic target.

scholarly journals Reciprocity between Skeletal Muscle AMPK Deletion and Insulin Action in Diet-Induced Obese Mice

2020 ◽  
Author(s):  
Ada Admin ◽  
Louise Lantier ◽  
Ashley S. Williams ◽  
Ian M.Williams ◽  
Amanda Guerin ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Insulin Signaling ◽  
Insulin Action ◽  
Energy State ◽  
Energy Charge ◽  
Ampk Signaling ◽  
Diet Induced Obesity ◽  
Energy Sensor ◽  
Amp Activated Protein Kinase

Insulin resistance due to overnutrition places a burden on energy-producing pathways in skeletal muscle (SkM). Nevertheless, energy state is not compromised. The hypothesis that the energy sensor AMP-activated protein kinase (AMPK) is necessary to offset the metabolic burden of overnutrition was tested using chow-fed and high fat (HF)-fed SkM-specific AMPKa1a2 knockout (mdKO) mice and AMPKa1a2lox/lox littermates (WT). Lean mdKO and WT mice were phenotypically similar. HF-fed mice were equally obese and maintained lean mass regardless of genotype. Results did not support the hypothesis that AMPK is protective during overnutrition. Paradoxically, mdKO mice were more insulin sensitive. Insulin-stimulated SkM glucose uptake was ~two-fold greater in mdKO mice in vivo. Furthermore, insulin signaling, SkM GLUT4 translocation, hexokinase activity, and glycolysis were increased. AMPK and insulin signaling intersect at mTOR, a critical node for cell proliferation and survival. Basal mTOR activation was reduced by 50% in HF-fed mdKO mice, but was normalized by insulin-stimulation. Mitochondrial function was impaired in mdKO mice, but energy charge was preserved by AMP deamination. Results show a surprising reciprocity between SkM AMPK signaling and insulin action that manifests with diet-induced obesity, as insulin action is preserved to protect fundamental energetic processes in the muscle.

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