AMP-activated Protein Kinase Plays a Role in the Control of Food Intake

Andersson, Ulrika; Filipsson, Karin; Abbott, Caroline R.; Woods, Angela; Smith, Kirk P.; Bloom, Stephen R.; Carling, David; Small, Caroline J.

doi:10.1074/jbc.c300557200

Cited by 686 publications

(614 citation statements)

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“…There is also widespread agreement that treatments which activate AMPK in the hypothalamus, such as infusion with the nucleoside 5-aminoimidazole-4-carboxamide riboside, treatment with the gut hormone ghrelin or cannabinoids, or hypoglycaemia, all increase food intake in rodents (30)(31)(32) .…”

Section: Regulation Of Amp-activated Protein Kinase By Adipokines Andmentioning

confidence: 99%

Energy sensing by the AMP-activated protein kinase and its effects on muscle metabolism

Hardie

2010

Proc. Nutr. Soc.

119

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The AMP-activated protein kinase (AMPK) is a sensor of cellular energy status, and a regulator of energy balance at both the cellular and whole body levels. Although ubiquitously expressed, its function is best understood in skeletal muscle. AMPK contains sites that reversibly bind AMP or ATP, with an increase in cellular AMP :ATP ratio (signalling a fall in cellular energy status) switching on the kinase. In muscle, AMPK activation is therefore triggered by sustained contraction, and appears to be particularly important in the metabolic changes that occur in the transition from resistance to endurance exercise. Once activated, AMPK switches on catabolic processes that generate ATP, while switching off energy-requiring processes not essential in the short term. Thus, it acutely activates glucose uptake (by promoting translocation of the transporter GLUT4 to the membrane) and fatty acid oxidation, while switching off glycogen synthesis and protein synthesis (the later via inactivation of the mammalian target-ofrapamycin pathway). Prolonged AMPK activation also causes some of the chronic adaptations to endurance exercise, such as increased GLUT4 expression and mitochondrial biogenesis. AMPK contains a glycogen-binding domain that causes a sub-fraction to bind to the surface of the glycogen particle, and it can inhibit glycogen synthesis by phosphorylating glycogen synthase. We have shown that AMPK is inhibited by exposed non-reducing ends in glycogen. We are working on the hypothesis that this ensures that glycogen synthesis is rapidly activated when glycogen becomes depleted after exercise, but is switched off again as soon as glycogen stores are replenished. Muscle: Exercise: Type 2 diabetes: NutraceuticalsAnimal cells take up fuel molecules such as glucose or fatty acids, and oxidise them to CO 2 via the process of catabolism. Much of the energy released during this process is used to convert ADP to ATP, which can be likened to the chemicals in a rechargeable battery. Extending this analogy, catabolism charges up the battery by converting ADP to ATP, whereas most other cellular activities (e.g. growth, division, secretion and movement) require energy and are driven by the conversion of ATP back to ADP, thus draining the battery. Just as machines that utilise rechargeable batteries (such as laptop computers or electric cars) require systems to monitor the state of the battery, cells require systems to monitor their ATP : ADP ratio and match the rates of uptake and consumption of carbon nutrients to the rate of ATP utilisation. The topic of this review is the AMP-activated protein kinase (AMPK), which is the major system responsible for achieving this task in eukaryotes. Researchers who wish to understand disorders of energy balance, such as obesity and type-2 diabetes, have been particularly interested in the system. Protein kinases, including AMPK, are signalling enzymes that modify the function of target proteins by transferring phosphate groups from ATP to side chains of specific amino acids, usually serine o...

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Section: Regulation Of Amp-activated Protein Kinase By Adipokines Andmentioning

confidence: 99%

Energy sensing by the AMP-activated protein kinase and its effects on muscle metabolism

Hardie

2010

Proc. Nutr. Soc.

119

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“…2,3 We and other laboratories have shown that hypothalamic AMPK plays a major role in the regulation of organism's energy balance. [4][5][6] Our interest in hypothalamic AMPK grew from our work with C75, a synthetic molecule that inhibits fatty acid synthase (FAS) 7 and stimulates carnitine palmitoyltransferase-1 (CPT-1) and beta-oxidation of fatty acids. [8][9][10] Fatty acid metabolic pathways are poised at a crossroads of energy deficit and energy surplus, with the potential to either use or make the high-energy molecule ATP.…”

Section: Introductionmentioning

confidence: 99%

“…2,31 Hormones and pharmacological agents modulate AMPK activity in muscle, liver and hypothalamus to promote fatty acid oxidation, glucose utilization and feeding responses. [4][5][6]36,37 Physiological stimuli can activate AMPK to promote tissue-specific responses such as skeletal muscle glucose uptake and glycolysis through glucose transporter translocation and 6-phosphofructo-2-kinase kinase activity, respectively, and fatty acid oxidation. 32,33,38 Liver AMPK inhibits fatty acid and cholesterol biosynthesis by phosphorylating and inactivating ACC and 3-hydroxy-3-methylglutaryl-coenzyme A reductase.…”

Section: Introductionmentioning

confidence: 99%

“…Once we knew that C75 altered pAMPK in neurons in vitro, 8 we altered the brain and hypothalamic AMPK in mice using well-known pharmacological tools, and fed and fasted states, to demonstrate that AMPK was a physiological mediator of C75's effects. 4 Other research groups also altered hypothalamic AMPK activity using genetic approaches 5 or peripheral hormones 5,6 to alter hypothalamic AMPK activity. These studies suggest that hypothalamic AMPK controls energy expenditure and fuel utilization as well.…”

Section: Introductionmentioning

confidence: 99%

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AMP-activated protein kinase in the brain

Ronnett

2008

Int J Obes

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Since its discovery as an important regulator of fuel utilization in the periphery, AMP-activated protein kinase (AMPK) has become a contender for many important cell-intrinsic and organismal roles regarding energy balance in the central nervous system. The challenge will be to delineate the mechanisms by which neuronal AMPK can respond to cellular energy requirements as well as whole body energy demands. Thus, under physiological conditions in the brain, hypothalamic AMPK responds to changes in energy balance/food intake, whereas under pathological conditions, AMPK responds globally in the brain to energy challenge. Modulation of fatty acid metabolism affects energy balance in a context-specific manner and may provide an insight into other mechanisms for selective activation or inhibition of AMPK activity for therapeutic applications.

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“…It has been demonstrated that administration of ghrelin to rats affects AMPK activity, although this effect is tissue-specific. In the hypothalamus, central and peripheral ghrelin treatments enhance protein levels of AMPK and this activation and alterations on lipid metabolism mediate the Page 17 of 37 A c c e p t e d M a n u s c r i p t 17 orexigenic effects of ghrelin (Andersson et al 2004;Kohno et al 2008;Kola et al 2005Kola et al , 2008Lopez et al 2008). In fed animals peripheral chronic and acute ghrelin treatments provoked AMPK activation in the heart, while in liver and adipose tissue it was inhibited and no effect was detected on skeletal muscle (Barazzoni et al 2005;Kola et al 2005).…”

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confidence: 99%

Ghrelin neutralization during fasting-refeeding cycle impairs the recuperation of body weight and alters hepatic energy metabolism

Sangiao‐Alvarellos

Helmling

Vázquez

et al. 2011

Molecular and Cellular Endocrinology

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Ghrelin neutralization during fasting-refeeding cycle impairs the recuperation of body weight and alters hepatic energy metabolism.. Molecular and Cellular Endocrinology, Elsevier, 2011, 335 (2) This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.Page 1 of 37A c c e p t e d M a n u s c r i p t A c c e p t e d M a n u s c r i p t 2 ABSTRACT Ghrelin, a hormone whose levels increase during food deprivation, plays a pivotal role in the regulation of food intake, energy metabolism and storage, as well as in insulin sensitivity. Here, we investigated the effects of acyl-ghrelin neutralization with the acyl-ghrelin-binding compound NOX-B11(2) during the fasting-refeeding cycle. Our data demonstrate that ghrelin neutralization with NOX-B11(2) impairs recuperation of lost body weight after food deprivation. Analysis of enzymes involved in glucose and lipid metabolism in liver of fed, fasted and refed rats revealed that neutralization of acyl-ghrelin resulted in minor decreases in the enzymes of glycolytic and lipogenic pathways during fasting. However, during refeeding these enzymes as well as glycogen levels recovered more slowly when acyl-ghrelin was blocked. The high levels of ghrelin in response to food deprivation may contribute to an adequate decrease in hepatic glycolytic and lipogenic enzymes and aid in the recovery of body weight and energetic reserves once food becomes available after the fasting period.

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AMP-activated Protein Kinase Plays a Role in the Control of Food Intake

Cited by 686 publications

References 28 publications

Energy sensing by the AMP-activated protein kinase and its effects on muscle metabolism

Energy sensing by the AMP-activated protein kinase and its effects on muscle metabolism

AMP-activated protein kinase in the brain

Ghrelin neutralization during fasting-refeeding cycle impairs the recuperation of body weight and alters hepatic energy metabolism

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