Effects of thyroid state on AMP-activated protein kinase and acetyl-CoA carboxylase expression in muscle

2002 ◽  
Vol 93 (6) ◽  
pp. 2081-2088 ◽  
Author(s):  
S. H. Park ◽  
S. R. Paulsen ◽  
S. R. Gammon ◽  
K. J. Mustard ◽  
D. G. Hardie ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Thyroid Hormones ◽  
Acetyl Coa Carboxylase ◽  
Acetyl Coa ◽  
Western Blots ◽  
Thyroid State ◽  
Α Subunit ◽  
Downstream Target ◽  
Upstream Kinase ◽  
Amp Activated Protein Kinase

AMP-activated protein kinase (AMPK) consists of three subunits: α, β, and γ. Two isoforms exist for the α-subunit (α1 and α2), two for the β-subunit (β1 and β2), and three for the γ-subunit (γ1, γ2, and γ3). Although the specific roles of the β- and γ-subunits are not well understood, the α-subunit isoforms contain the catalytic site and also the phosphorylation/activation site for the upstream kinase. This study was designed to determine the role of thyroid hormones in controlling expression levels of these AMPK subunits and of one downstream target, acetyl-CoA carboxylase (ACC), in muscle. AMPK subunit and ACC levels were determined by Western blots in control rats, in rats given 0.01% propylthiouracil (PTU) in drinking water for 3 wk, and in rats given 3 mg of thyroxine and 1 mg of triiodothyronine per kilogram chow for 1 or 3 wk. In gastrocnemius muscle, all isoforms of AMPK subunits were significantly increased in rats given thyroid hormones for 3 wk vs. those treated with PTU. Similar patterns were seen in individual muscle types. Expression of muscle ACC was also significantly increased in response to 3 wk of treatment with excess thyroid hormones. Muscle content of malonyl-CoA was elevated in PTU-treated rats and depressed in thyroid hormone-treated rats. These data provide evidence that skeletal muscle AMPK subunit and ACC expression is partially under the control of thyroid hormones.

Long-term regulation of AMP-activated protein kinase and acetyl-CoA carboxylase in skeletal muscle

2003 ◽  
Vol 31 (1) ◽  
pp. 182-185 ◽  
Author(s):  
W.W. Winder ◽  
D.G. Hardie ◽  
K.J. Mustard ◽  
L.J. Greenwood ◽  
B.E. Paxton ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Kinase ◽  
Fold Increase ◽  
Acid Oxidation ◽  
Acetyl Coa Carboxylase ◽  
Acetyl Coa ◽  
Thyroid State ◽  
Hormone Synthesis ◽  
Subunit Isoforms ◽  
Amp Activated Protein Kinase

Evidence is accumulating for roles of AMP-activated protein kinase (AMPK) in controlling glucose uptake, fatty acid oxidation and gene expression in skeletal muscle. Relatively little is known, however, about the control of expression of the AMPK subunit isoforms. Marked differences are noted in subunit expression as a function of muscle fibre type. Expression of the γ3 subunit isoform increases in fast-twitch red fibres of the rat in response to training. All subunit isoforms are expressed to a lesser extent in rats treated with propylthiouracil (PTU; an inhibitor of thyroid hormone synthesis) for 3 weeks compared with rats given excess thyroid hormones for 3 weeks. An approx. 2-fold increase in acetyl-CoA carboxylase was observed in gastrocnemius of hyperthyroid rats compared with experimentally hypothyroid rats. Thyroid state therefore appears to be one important factor controlling expression of these proteins in skeletal muscle.

Effect of phosphorylation by AMP-activated protein kinase on palmitoyl-CoA inhibition of skeletal muscle acetyl-CoA carboxylase

2005 ◽  
Vol 98 (4) ◽  
pp. 1221-1227 ◽  
Author(s):  
D. S. Rubink ◽  
W. W. Winder
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acid ◽  
Protein Kinase ◽  
Fatty Acid Oxidation ◽  
Acid Oxidation ◽  
Acetyl Coa Carboxylase ◽  
Acetyl Coa ◽  
Oxidation Rates ◽  
Malonyl Coa ◽  
Amp Activated Protein Kinase

AMP-activated protein kinase (AMPK) has previously been demonstrated to phosphorylate and inactivate skeletal muscle acetyl-CoA carboxylase (ACC), the enzyme responsible for synthesis of malonyl-CoA, an inhibitor of carnitine palmitoyltransferase 1 and fatty acid oxidation. Contraction-induced activation of AMPK with subsequent phosphorylation/inactivation of ACC has been postulated to be responsible in part for the increase in fatty acid oxidation that occurs in muscle during exercise. These studies were designed to answer the question: Does phosphorylation of ACC by AMPK make palmitoyl-CoA a more effective inhibitor of ACC? Purified rat muscle ACC was subjected to phosphorylation by AMPK. Activity was determined on nonphosphorylated and phosphorylated ACC preparations at acetyl-CoA concentrations ranging from 2 to 500 μM and at palmitoyl-CoA concentrations ranging from 0 to 100 μM. Phosphorylation resulted in a significant decline in the substrate saturation curve at all palmitoyl-CoA concentrations. The inhibitor constant for palmitoyl-CoA inhibition of ACC was reduced from 1.7 ± 0.25 to 0.85 ± 0.13 μM as a consequence of phosphorylation. At 0.5 mM citrate, ACC activity was reduced to 13% of control values in response to the combination of phosphorylation and 10 μM palmitoyl-CoA. Skeletal muscle ACC is more potently inhibited by palmitoyl-CoA after having been phosphorylated by AMPK. This may contribute to low-muscle malonyl-CoA values and increasing fatty acid oxidation rates during long-term exercise when plasma fatty acid concentrations are elevated.

scholarly journals Glucagon Activates the AMP‐Activated Protein Kinase/Acetyl‐CoA Carboxylase Pathway in Adipocytes

2010 ◽  
Vol 24 (S1) ◽  
Author(s):  
I‐Chen Peng ◽  
Zhen Chen ◽  
Pang‐Hung Hsu ◽  
Mei‐I Su ◽  
Ming‐Daw Tsai ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Acetyl Coa Carboxylase ◽  
Acetyl Coa ◽  
Amp Activated Protein Kinase

Hypoxia and AMP independently regulate AMP-activated protein kinase activity in heart

2005 ◽  
Vol 288 (5) ◽  
pp. H2412-H2421 ◽  
Author(s):  
Markus Frederich ◽  
Li Zhang ◽  
James A. Balschi
Keyword(s):  
Protein Kinase ◽  
Metabolic Inhibitors ◽  
Protein Kinase Activity ◽  
Α Subunit ◽  
Rat Hearts ◽  
Upstream Kinase ◽  
Ampk Activity ◽  
Amp Activated Protein Kinase

The hypothesis was tested that hypoxia increases AMP-activated protein kinase (AMPK) activity independently of AMP concentration ([AMP]) in heart. In isolated perfused rat hearts, cytosolic [AMP] was changed from 0.2 to 16 μM using metabolic inhibitors during both normal oxygenation (95% O2-5% CO2, normoxia) and limited oxygenation (95% N2-5% CO2, hypoxia). Total AMPK activity measured in vitro ranged from 2 to 40 pmol·min−1·mg protein−1 in normoxic hearts and from 5 to 55 pmol·min−1·mg protein−1 in hypoxic hearts. The dependence of the in vitro total AMPK activity on the in vivo cytosolic [AMP] was determined by fitting the measurements from individual hearts to a hyperbolic equation. The [AMP] resulting in half-maximal total AMPK activity ( A0.5) was 3 ± 1 μM for hypoxic hearts and 28 ± 13 μM for normoxic hearts. The A0.5 for α2-isoform AMPK activity was 2 ± 1 μM for hypoxic hearts and 13 ± 8 μM for normoxic hearts. Total AMPK activity correlated with the phosphorylation of the Thr172 residue of the AMPK α-subunit. In potassium-arrested hearts perfused with variable O2 content, α-subunit Thr172 phosphorylation increased at O2 ≤ 21% even though [AMP] was <0.3 μM. Thus hypoxia or O2 ≤ 21% increased AMPK phosphorylation and activity independently of cytosolic [AMP]. The hypoxic increase in AMPK activity may result from either direct phosphorylation of Thr172 by an upstream kinase or reduction in the A0.5 for [AMP].

Skeletal muscle basal AMP-activated protein kinase activity is chronically elevated in alloxan-diabetic dogs: impact of exercise

2003 ◽  
Vol 95 (4) ◽  
pp. 1523-1530 ◽  
Author(s):  
Michael J. Christopher ◽  
Zhi-Ping Chen ◽  
Christian Rantzau ◽  
Bruce E. Kemp ◽  
Frank P. Alford
Keyword(s):  
Skeletal Muscle ◽  
Protein Kinase ◽  
Vastus Lateralis ◽  
Glucose Disposal ◽  
Protein Kinase Activity ◽  
Acetyl Coa Carboxylase ◽  
Acetyl Coa ◽  
Peripheral Tissues ◽  
Diabetic Dogs ◽  
Amp Activated Protein Kinase

The effect of diabetes and exercise on skeletal muscle (SkM) AMP-activated protein kinase (AMPK)α1 and -α2 activities and site-specific phosphorylation of acetyl-CoA carboxylase was examined in the same six dogs before alloxan (35 mg/kg)-induced diabetes (C) and after 4-5 wk of suboptimally controlled hyperglycemic and hypoinsulinemic diabetes (DHG) in the presence and absence of 300-min phlorizin (50 μg·kg-1·min-1)-induced “normoglycemia” (DNG). In each study, the dog underwent a 150-min [3-3H]glucose infusion period, followed by a 30-min treadmill exercise test (60-70% maximal oxygen capacity) to measure the rate of glucose disposal into peripheral tissues (Rdtissue). SkM biopsies were taken from the thigh (vastus lateralis) before and immediately after exercise. In the C and DHG states, the rise in plasma free fatty acids (FFA) with exercise (∼40%) was similar. In the DNG group, preexercise FFA were significantly higher, but the absolute rise in FFA with exercise was similar. However, the exercise-induced increment in Rdtissue was significantly blunted (by ∼40-50%) in the DNG group compared with the other states. In SkM, preexercise AMPKα1 and -α2 activities were significantly elevated (by ∼60-125%) in both diabetic states, but unlike the C group these activities did not rise further with exercise. Additionally, preexercise acetyl-CoA carboxylase phosphorylation in both diabetic states was elevated by ∼70-80%, but the increases with exercise were similar to the C group. Preexercise AMPKα1 and -α2 activities were negatively correlated with Rdtissue during exercise for the combined groups (both P < 0.02). In conclusion, the elevated preexercise SkM AMPKα1 and -α2 activities contribute to the ongoing basal supply of glucose and fatty acid metabolism in suboptimally controlled hypoinsulinemic diabetic dogs; but whether they also play a permissive role in the metabolic stress response to exercise remains uncertain.

Regulation of mammalian acetyl-CoA carboxylase

2002 ◽  
Vol 30 (6) ◽  
pp. 1059-1064 ◽  
Author(s):  
M. R. Munday
Keyword(s):  
Fatty Acid ◽  
Protein Kinase ◽  
Critical Role ◽  
Physiological Role ◽  
Acid Synthesis ◽  
Acid Oxidation ◽  
Acetyl Coa Carboxylase ◽  
Acetyl Coa ◽  
Dependent Protein ◽  
Amp Activated Protein Kinase

Acetyl-CoA carboxylase (ACC) plays a critical role in the regulation of fatty acid metabolism and its two isoforms, ACCα and ACCβ, appear to have distinct functions in the control of fatty acid synthesis and fatty acid oxidation, respectively. They are regulated by similar short-term mechanisms of allosteric activation by citrate, and reversible phosphorylation and inactivation, and there is clearly interaction between these mechanisms. AMP-activated protein kinase is the important physiological ACC kinase for both isoforms and yet there is a potential physiological role for cAMP-dependent protein kinase in the hormonally mediated inactivation of ACCα, and phosphorylation of ACCβ in its unique N-terminus.

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