AMP-activated protein kinase regulates the expression of monocarboxylate transporter 4 in skeletal muscle

The objective of this study was to evaluate the antihyperlipidemic and antihyperglycemic effects and mechanism of the extract ofClitocybe nuda(CNE), in high-fat- (HF-) fed mice. C57BL/6J was randomly divided into two groups: the control (CON) group was fed with a low-fat diet, whereas the experimental group was fed with a HF diet for 8 weeks. Then, the HF group was subdivided into five groups and was given orally CNE (including C1: 0.2, C2: 0.5, and C3: 1.0 g/kg/day extracts) or rosiglitazone (Rosi) or vehicle for 4 weeks. CNE effectively prevented HF-diet-induced increases in the levels of blood glucose, triglyceride, insulin (P<0.001,P<0.01,P<0.05, resp.) and attenuated insulin resistance. By treatment with CNE, body weight gain, weights of white adipose tissue (WAT) and hepatic triacylglycerol content were reduced; moreover, adipocytes in the visceral depots showed a reduction in size. By treatment with CNE, the protein contents of glucose transporter 4 (GLUT4) were significantly increased in C3-treated group in the skeletal muscle. Furthermore, CNE reduces the hepatic expression of glucose-6-phosphatase (G6Pase) and glucose production. CNE significantly increases protein contents of phospho-AMP-activated protein kinase (AMPK) in the skeletal muscle and adipose and liver tissues. Therefore, it is possible that the activation of AMPK by CNE leads to diminished gluconeogenesis in the liver and enhanced glucose uptake in skeletal muscle. It is shown that CNE exhibits hypolipidemic effect in HF-fed mice by increasing ATGL expression, which is known to help triglyceride to hydrolyze. Moreover, antidiabetic properties of CNE occurred as a result of decreased hepatic glucose production via G6Pase downregulation and improved insulin sensitization. Thus, amelioration of diabetic and dyslipidemic states by CNE in HF-fed mice occurred by regulation of GLUT4, G6Pase, ATGL, and AMPK phosphorylation.

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Front Cover: Goat Milk Improves Glucose Homeostasis via Enhancement of Hepatic and Skeletal Muscle AMP‐Activated Protein Kinase Activation and Modulation of Gut Microbiota in Streptozocin‐Induced Diabetic Rats

Molecular Nutrition & Food Research ◽

10.1002/mnfr.202170012 ◽

2021 ◽

Vol 65 (6) ◽

pp. 2170012

Author(s):

Wei Liu ◽

Yalin Zhou ◽

Han Sun ◽

Ruijun Li ◽

Yong Qin ◽

...

Keyword(s):

Skeletal Muscle ◽

Protein Kinase ◽

Gut Microbiota ◽

Glucose Homeostasis ◽

Goat Milk ◽

Diabetic Rats ◽

Front Cover ◽

Kinase Activation ◽

Protein Kinase Activation ◽

Amp Activated Protein Kinase

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Expression of Uncoupling Protein 3 and GLUT4 Gene in Skeletal Muscle of Preterm Newborns: Possible Control by AMP-Activated Protein Kinase

Pediatric Research ◽

10.1203/01.pdr.0000242301.64555.e2 ◽

2006 ◽

Vol 60 (5) ◽

pp. 569-575 ◽

Cited By ~ 8

Author(s):

Petr Brauner ◽

Pavel Kopecky ◽

Pavel Flachs ◽

Ondrej Kuda ◽

Jaroslav Vorlicek ◽

...

Keyword(s):

Skeletal Muscle ◽

Protein Kinase ◽

Uncoupling Protein ◽

Uncoupling Protein 3 ◽

Amp Activated Protein Kinase ◽

Preterm Newborns

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Role of the AMP-activated protein kinase in regulating fatty acid metabolism during exerciseThis paper is one of a selection of papers published in this Special Issue, entitled 14th International Biochemistry of Exercise Conference – Muscles as Molecular and Metabolic Machines, and has undergone the Journal’s usual peer review process.

Applied Physiology Nutrition and Metabolism ◽

10.1139/h09-009 ◽

2009 ◽

Vol 34 (3) ◽

pp. 315-322 ◽

Cited By ~ 26

Author(s):

Gregory R. Steinberg

Keyword(s):

Skeletal Muscle ◽

Fatty Acids ◽

Adipose Tissue ◽

Fatty Acid ◽

Protein Kinase ◽

Fatty Acid Metabolism ◽

Acid Metabolism ◽

Moderate Intensity ◽

Amp Activated Protein Kinase

During moderate-intensity exercise, fatty acids are the predominant substrate for working skeletal muscle. The release of fatty acids from adipose tissue stores, combined with the ability of skeletal muscle to actively fine tune the gradient between fatty acid and carbohydrate metabolism, depending on substrate availability and energetic demands, requires a coordinated system of metabolic control. Over the past decade, since the discovery that AMP-activated protein kinase (AMPK) was increased in accordance with exercise intensity, there has been significant interest in the proposed role of this ancient stress-sensing kinase as a critical integrative switch controlling metabolic responses during exercise. In this review, studies examining the role of AMPK as a regulator of fatty acid metabolism in both adipose tissue and skeletal muscle during exercise will be discussed. Exercise induces activation of AMPK in adipocytes and regulates triglyceride hydrolysis and esterfication through phosphorylation of hormone sensitive lipase (HSL) and glycerol-3-phosphate acyl-transferase, respectively. In skeletal muscle, exercise-induced activation of AMPK is associated with increases in fatty acid uptake, phosphorylation of HSL, and increased fatty acid oxidation, which is thought to occur via the acetyl-CoA carboxylase-malony-CoA-CPT-1 signalling axis. Despite the importance of AMPK in regulating fatty acid metabolism under resting conditions, recent evidence from transgenic models of AMPK deficiency suggest that alternative signalling pathways may also be important for the control of fatty acid metabolism during exercise.

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Exercise and MEF2–HDAC interactions

Applied Physiology Nutrition and Metabolism ◽

10.1139/h07-082 ◽

2007 ◽

Vol 32 (5) ◽

pp. 852-856 ◽

Cited By ~ 21

Author(s):

Sean L. McGee

Keyword(s):

Skeletal Muscle ◽

Protein Kinase ◽

Nuclear Export ◽

Energy Homeostasis ◽

Whole Body ◽

Positive Health ◽

Exercise Induced ◽

Amp Activated Protein Kinase ◽

Body Energy ◽

Skeletal Muscle Adaptations

Exercise increases the metabolic capacity of skeletal muscle, which improves whole-body energy homeostasis and contributes to the positive health benefits of exercise. This is, in part, mediated by increases in the expression of a number of metabolic enzymes, regulated largely at the level of transcription. At a molecular level, many of these genes are regulated by the class II histone deacetylase (HDAC) family of transcriptional repressors, in particular HDAC5, through their interaction with myocyte enhancer factor 2 transcription factors. HDAC5 kinases, including 5′-AMP-activated protein kinase and protein kinase D, appear to regulate skeletal muscle metabolic gene transcription by inactivating HDAC5 and inducing HDAC5 nuclear export. These mechanisms appear to participate in exercise-induced gene expression and could be important for skeletal muscle adaptations to exercise.

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AMP-activated protein kinase activity and glucose uptake in rat skeletal muscle

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.2001.280.5.e677 ◽

2001 ◽

Vol 280 (5) ◽

pp. E677-E684 ◽

Cited By ~ 152

Author(s):

Nicolas Musi ◽

Tatsuya Hayashi ◽

Nobuharu Fujii ◽

Michael F. Hirshman ◽

Lee A. Witters ◽

...

Keyword(s):

Skeletal Muscle ◽

Protein Kinase ◽

Glucose Uptake ◽

Muscle Contractions ◽

Treadmill Running ◽

Dependent Manner ◽

Rat Skeletal Muscle ◽

Amp Activated Protein Kinase ◽

Dose Dependent

The AMP-activated protein kinase (AMPK) has been hypothesized to mediate contraction and 5-aminoimidazole-4-carboxamide 1-β-d-ribonucleoside (AICAR)-induced increases in glucose uptake in skeletal muscle. The purpose of the current study was to determine whether treadmill exercise and isolated muscle contractions in rat skeletal muscle increase the activity of the AMPKα1 and AMPKα2 catalytic subunits in a dose-dependent manner and to evaluate the effects of the putative AMPK inhibitors adenine 9-β-d-arabinofuranoside (ara-A), 8-bromo-AMP, and iodotubercidin on AMPK activity and 3- O-methyl-d-glucose (3-MG) uptake. There were dose-dependent increases in AMPKα2 activity and 3-MG uptake in rat epitrochlearis muscles with treadmill running exercise but no effect of exercise on AMPKα1 activity. Tetanic contractions of isolated epitrochlearis muscles in vitro significantly increased the activity of both AMPK isoforms in a dose-dependent manner and at a similar rate compared with increases in 3-MG uptake. In isolated muscles, the putative AMPK inhibitors ara-A, 8-bromo-AMP, and iodotubercidin fully inhibited AICAR-stimulated AMPKα2 activity and 3-MG uptake but had little effect on AMPKα1 activity. In contrast, these compounds had absent or minimal effects on contraction-stimulated AMPKα1 and -α2 activity and 3-MG uptake. Although the AMPKα1 and -α2 isoforms are activated during tetanic muscle contractions in vitro, in fast-glycolytic fibers, the activation of AMPKα2-containing complexes may be more important in regulating exercise-mediated skeletal muscle metabolism in vivo. Development of new compounds will be required to study contraction regulation of AMPK by pharmacological inhibition.

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