Phosphorylation-activity relationships of AMPK and acetyl-CoA carboxylase in muscle

Park, S. H.; Gammon, S. R.; Knippers, J. D.; Paulsen, S; Rubink, D. S.; Winder, W. W.

doi:10.1152/japplphysiol.00071.2002

Cited by 269 publications

(220 citation statements)

References 54 publications

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“…Ceramide content in gastrocnemius muscle was similar between transgenic and nontransgenic WT and ob/ob mice, confirming previous reports (42,43). However, phosphorylation of ACC, a downstream target of AMPK (44), was increased in g 3 R225Q transgenic…”

Section: R225qsupporting

confidence: 89%

Effects of AMPK Activation on Insulin Sensitivity and Metabolism in Leptin-Deficient ob/ob Mice

et al. 2014

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AMP-activated protein kinase (AMPK) is a heterotrimeric complex, composed of a catalytic subunit (a) and two regulatory subunits (b and g), which act as a metabolic sensor to regulate glucose and lipid metabolism. A mutation in the g 3 subunit (AMPKg 3 R225Q) increases basal AMPK phosphorylation, while concomitantly reducing sensitivity to AMP. AMPKg 3 R225Q (g 3 R225Q ) transgenic mice are protected against dietary-induced triglyceride accumulation and insulin resistance. We determined whether skeletal muscle-specific expression of AMPKg 3 R225Q prevents metabolic abnormalities in leptin-deficient ob/ob (ob/ob-g 3 R225Q ) mice. Glycogen content was increased, triglyceride content was decreased, and diacylglycerol and ceramide content were unaltered in gastrocnemius muscle from ob/ob-g 3 R225Q mice, whereas glucose tolerance was unaltered. Insulinstimulated glucose uptake in extensor digitorum longus muscle during the euglycemic-hyperinsulinemic clamp was increased in lean g 3 R225Q mice, but not in ob/ob-g 3 R225Q mice. Acetyl-CoA carboxylase phosphorylation was increased in gastrocnemius muscle from g 3 R225Q mutant mice independent of adiposity. Glycogen and triglyceride content were decreased after leptin treatment (5 days) in ob/ob mice, but not in ob/ob-g 3 R225Q mice. In conclusion, metabolic improvements arising from muscle-specific expression of AMPKg 3 R225Q are insufficient to ameliorate insulin resistance and obesity in leptin-deficient mice. Central defects due to leptin deficiency may override any metabolic benefit conferred by peripheral overexpression of the AMPKg 3 R225Q mutation.

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Section: R225qsupporting

confidence: 89%

Effects of AMPK Activation on Insulin Sensitivity and Metabolism in Leptin-Deficient ob/ob Mice

et al. 2014

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“…Frederich et al (34) show a negative correlation between the activities of AMPK and ACC in the heart. The same has been shown for AMPK-induced phosphorylation in exercised skeletal muscle (35). However, newer data suggest a differential regulation of AMPK and ACC that depends on the time course and the intensity of exercise.…”

Section: Discussionsupporting

confidence: 58%

Metabolic Switch and Hypertrophy of Cardiomyocytes following Treatment with Angiotensin II Are Prevented by AMP-activated Protein Kinase

Stuck¹,

Lenski²,

Böhm

et al. 2008

Journal of Biological Chemistry

106

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Left ventricular (LV)3 hypertrophy is a major independent risk factor for premature death (1). Myocardial hypertrophy is a response to hemodynamic overload such as hypertension or aortic valve stenosis. A fundamental mechanism leading to both hypertrophy and subsequent heart failure is activation of the renin-angiotensin-aldosteron system. All components of the system are expressed at the mRNA and protein levels in the heart (2), circulating plasma concentrations of angiotensin II (Ang II) correlate to the extend of LV hypertrophy (3) and the progression to heart failure (4), and the increase in left ventricular mass can be prevented with an angiotensin converting enzyme inhibitor or angiotensin receptor blocker (5).Molecular mechanisms by which the renin-angiotensin-aldosteron system evokes cardiac hypertrophy are activation of protein kinase cascades, initiation of a fetal-like gene program, impaired calcium handling, and increased production of reactive oxygen species (6). Changes in substrate utilization occurring during cardiomyocyte hypertrophy are not well known, and their consequences on cardiomyocyte metabolism and energy supply are not completely understood. A shift in the substrate pattern from fatty acid oxidation to glucose utilization appears to occur in different forms of LV hypertrophy (7), but whether metabolic changes precede hypertrophy or result from it and which pathways are involved is unknown.A key metabolic regulator is AMP-activated protein kinase (AMPK), a heterotrimeric protein that is centrally involved in controlling cellular energy homeostasis. Its activation through metabolic stress stimulates energy-generating processes and has been shown to regulate hypertrophy-regulating genes in several models (8). When AMPK binds AMP the ␣-subunit gets sensitized to phosphorylation by upstream kinases and increases kinase activity. Upon activation AMPK increases fatty acid oxidation by phosphorylating ACC, in turn decreasing malonyl-CoA content and activating carnitine palmitoyltransferase-I. In several tissues AMPK has been shown to also regulate glucose metabolism (9) and translocation of glucose transporter 4 (GLUT4) to the plasma membrane (10). Activated AMPK mediates changes in protein expression through regu-

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“…This finding implies a common role of dietary selenium in the overall fuel nutrient metabolism and is reinforced by the high-selenium diet-induced increases in AMPKa and phosphor-AMPKa (activation of the kinase) and decreases in phosphor-AMPKb (inactivation of the kinase) in the liver (48). Because AMPK is a key upstream regulator of PEPCK, SREBP1, p53, ACC, PPARG, CYP7A1, and mTOR (57)(58)(59), the stimulation of this enzyme could help explain the accelerated lipogenesis and protein synthesis in the liver.…”

Section: Discussionmentioning

confidence: 90%

“…The increased total ACC should also support lipogenesis, although the increased phosphor-ACC might inhibit ACC complex activity (48). Because the CYP7A1 enzyme is involved in the cholesterol hydrolysis pathway (49), the decrease of 90% in its mRNA level by the high-selenium diet might contribute to the accumulation of hepatic TC.…”

Section: Discussionmentioning

confidence: 99%

High Dietary Selenium Intake Alters Lipid Metabolism and Protein Synthesis in Liver and Muscle of Pigs

Zhao

Barcus

Kim

et al. 2016

The Journal of Nutrition

103

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Phosphorylation-activity relationships of AMPK and acetyl-CoA carboxylase in muscle

Cited by 269 publications

References 54 publications

Effects of AMPK Activation on Insulin Sensitivity and Metabolism in Leptin-Deficient ob/ob Mice

Effects of AMPK Activation on Insulin Sensitivity and Metabolism in Leptin-Deficient ob/ob Mice

Metabolic Switch and Hypertrophy of Cardiomyocytes following Treatment with Angiotensin II Are Prevented by AMP-activated Protein Kinase

High Dietary Selenium Intake Alters Lipid Metabolism and Protein Synthesis in Liver and Muscle of Pigs

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