Regulation of AMP-activated protein kinase and acetyl-CoA carboxylase phosphorylation by palmitate in skeletal muscle cells

Fediuc, Sergiu; Gaidhu, Mandeep Pinky; Ceddia, Rolando B.

doi:10.1194/jlr.m500438-jlr200

Cited by 107 publications

(103 citation statements)

References 25 publications

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“…Previous reports observed different effects of lipids on AMPK activation in different tissues. Recently, it has been shown that increased FA availability stimulates AMPK activity in skeletal muscle both in vitro and in vivo (10,(24)(25)(26)(27). Likewise, a diminished AMPK phosphorylation in the liver was also supported by previous works showing that TG accumulation in the liver is in association with decreased AMPK activation (27,28).…”

Section: Discussionsupporting

confidence: 66%

Infusion of a Lipid Emulsion Modulates AMPK and Related Proteins in Rat Liver, Muscle, and Adipose Tissues

Anavi

Erez

Tirosh

et al. 2010

Obesity

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The primary objective of this study was to investigate the impact of lipid oversupply on the AMPK pathway in skeletal muscle, liver, and adipose tissue. Male Wistar rats were infused with lipid emulsion (LE) or phosphate-buffered saline for 5 h/day for 6 days. Muscles exposed to LE for 6 days exhibited increased AMPK and acetyl-CoA carboxylase (ACC) phosphorylation, along with a greater association between AMPK and Ca 2+ /calmodulin-dependent protein kinase kinase (CaMKK). No differences in muscle protein phosphatase 2C (PP2C) activity, LKB1 phosphorylation or AMPK and LKB1 association were observed. Muscle ACCβ, and adiponectin receptor 1 (AdipoR1) mRNA levels and PPARγ-co-activator 1α (PGC1α) protein levels were also increased in LE-treated rats. In contrast, AMPK and ACC phosphorylation decreased and PP2C activity increased in rat livers exposed to LE. Hepatic mRNA levels of ACCα, PPARα, AdipoR1, AdipoR2, and sterol regulatory element-binding protein-1c (SREBP1c) were also reduced after LE infusion. In adipose tissue, there was no significant alteration in AMPK or ACC phosphorylation. These results demonstrate that following lipid oversupply the AMPK pathway was enhanced in rat skeletal muscle while diminished in the liver and was unchanged in adipose tissue. CaMKK in skeletal muscle and PP2C in the liver, at least in part, appear to mediate these alterations. Alterations in AMPK pathway in the liver induced metabolic defects associated with lipid oversupply.

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Section: Discussionsupporting

confidence: 66%

Infusion of a Lipid Emulsion Modulates AMPK and Related Proteins in Rat Liver, Muscle, and Adipose Tissues

Anavi

Erez

Tirosh

et al. 2010

Obesity

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“…AMPK inhibition using compound-C reversed the effects of AICAR and NaN 3 by returning ventilatory burst durations and periods to control values. Because compound-C is a well known selective and ATP-competitive inhibitor of AMPK (Zhou et al, 2001;Fediuc et al, 2006), this indicates that AMPK is necessary for the switch to a slow rhythm.…”

Section: Discussionmentioning

confidence: 99%

Metabolic Stress Modulates Motor Patterning via AMP-Activated Protein Kinase

Rodgers-Garlick

Armstrong²,

Robertson³

2011

J. Neurosci.

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Neural circuits are especially vulnerable to metabolic stress. The locust (Locusta migratoria) responds to anoxia by entering a coma during which neural and muscular systems shut down. During anoxic coma, arrest of the ventilatory central pattern generator is tightly correlated with an abrupt spreading depression (SD)-like increase in extracellular potassium concentration within the metathoracic neuropile. We examined the role of the AMP-activated protein kinase (AMPK), an evolutionarily conserved sensor of cellular energy status, in anoxia-induced ventilatory arrest and SD-like events in the locust. Perfusion of sodium azide (NaN 3 ; mitochondrial toxin) induced SD, temporary coma, and profound changes in the ventilatory motor pattern characterized as a rapid rhythm before coma and a slower rhythm following recovery. AMPK activation using 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) mimicked the motor pattern changes induced by NaN 3 but did not induce SD and coma. The effects of NaN 3 on the ventilatory rhythm were reversed by perfusion of compound-C (AMPK inhibitor) or glucose, and the effects of AICAR were also reversed by compound-C, confirming the modulatory roles of AMPK and energy status. Ouabain-induced recurring SD was suppressed by inhibition of AMPK and exacerbated by its activation. We show that the motor pattern changes induced by metabolic stress are not the result of SD alone, but that AMPK is necessary and sufficient for these changes and that AMPK activity strongly influences susceptibility to SD.

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“…The phosphorylation of AMPK was determined by using a phospho-AMPK (Thr-172) antibody (1:1000 dilution) that detects AMPK-␣ only when activated by phosphorylation at threonine 172. ACC phosphorylation was detected using a phospho-ACC(Ser-79)-specific antibody (1:1000 dilution), which recognizes ACC when phosphorylated at Ser-79 (19). The presence of the catalytic subunits of ␣1 and ␣2 isoforms of AMPK was determined by using specific antibodies (1:1000 dilution).…”

Section: Western Blot Determination Of Ampk␣1 and -␣2 P-ampk And P-mentioning

confidence: 99%

“…After conjugation with albumin, the concentration of fatty acids in the solution was measured by using a nonesterified fatty acid (NEFA) kit (Wako Chemicals Inc., Richmond, VA). The stock solution was diluted into the final incubation medium to obtain palmitate and oleate concentrations of 200 M. Palmitate and oleate oxidation was measured by the production of 14 CO 2 from [1-14 C]palmitic acid (0.2 Ci/ml) and [1-14 C]oleic acid (0.2 Ci/ml) with nonlabeled palmitate and oleate present in the medium as described previously (15,16,19) with a few modifications. Briefly, cells (5% lipocrit, ϳ10 5 cells) were incubated for 1 h in 20-ml plastic scintillation flasks in the absence or presence of AICAR (2 mM), compound C (20 M), and compound C plus AICAR.…”

Section: Production Of 14 Co 2 From [1-14 C]palmitic Acid and [1-mentioning

confidence: 99%

“…14 C]Oleic Acid-Palmitate and oleate were conjugated with essentially fatty acid-free bovine serum albumin (BSA) to generate a stock solution of 12.5% (w/v) BSA, 6 mM fatty acid in serum-free medium as described previously (15,16,19). After conjugation with albumin, the concentration of fatty acids in the solution was measured by using a nonesterified fatty acid (NEFA) kit (Wako Chemicals Inc., Richmond, VA).…”

Section: Production Of 14 Co 2 From [1-14 C]palmitic Acid and [1-mentioning

confidence: 99%

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5-Aminoimidazole-4-carboxamide-1-β-D-ribofuranoside-induced AMP-activated Protein Kinase Phosphorylation Inhibits Basal and Insulin-stimulated Glucose Uptake, Lipid Synthesis, and Fatty Acid Oxidation in Isolated Rat Adipocytes

Gaidhu

Fediuc

Ceddia

2006

Journal of Biological Chemistry

103

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The objective of this study was to investigate the effects of 5-aminoimidazole-4-carboxamide-1-␤-D-ribofuranoside (AICAR)-induced AMP-activated protein kinase (AMPK) activation on basal and insulin-stimulated glucose and fatty acid metabolism in isolated rat adipocytes. AICAR-induced AMPK activation profoundly inhibited basal and insulin-stimulated glucose uptake, lipogenesis, glucose oxidation, and lactate production in fat cells. We also describe the novel findings that AICAR-induced AMPK phosphorylation significantly reduced palmitate (32%) and oleate uptake (41%), which was followed by a 50% reduction in palmitate oxidation despite a marked increase in AMPK and acetyl-CoA carboxylase phosphorylation. Compound C, a selective inhibitor of AMPK, not only completely prevented the inhibitory effect of AICAR on palmitate oxidation but actually caused a 2.2-fold increase in this variable. Compound C also significantly increased palmitate oxidation in the presence of inhibitory concentrations of malonyl-CoA and etomoxir indicating an increase in CPT1 activity. In contrast to skeletal muscle in which AMPK stimulates fatty acid oxidation to provide ATP as a fuel, we propose that AMPK activation inhibits lipogenesis and fatty acid oxidation in adipocytes. Inhibition of lipogenesis would conserve ATP under conditions of cellular stress, although suppression of intra-adipocyte oxidation would spare fatty acids for exportation to other tissues where their utilization is crucial for energy production. Additionally, the stimulatory effect of compound C on long chain fatty acid oxidation provides a novel pharmacological approach to promote energy dissipation in adipocytes, which may be of therapeutic importance for obesity and type II diabetes.

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Regulation of AMP-activated protein kinase and acetyl-CoA carboxylase phosphorylation by palmitate in skeletal muscle cells

Cited by 107 publications

References 25 publications

Infusion of a Lipid Emulsion Modulates AMPK and Related Proteins in Rat Liver, Muscle, and Adipose Tissues

Infusion of a Lipid Emulsion Modulates AMPK and Related Proteins in Rat Liver, Muscle, and Adipose Tissues

Metabolic Stress Modulates Motor Patterning via AMP-Activated Protein Kinase

5-Aminoimidazole-4-carboxamide-1-β-D-ribofuranoside-induced AMP-activated Protein Kinase Phosphorylation Inhibits Basal and Insulin-stimulated Glucose Uptake, Lipid Synthesis, and Fatty Acid Oxidation in Isolated Rat Adipocytes

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