Physiological and biochemical effects of iron deficiency on rat skeletal muscle

McLane, J. A.; Fell, R. D.; McKay, Roxane; Winder, W. W.; Brown, E. B.; Holloszy, John O.

doi:10.1152/ajpcell.1981.241.1.c47

Cited by 112 publications

(38 citation statements)

References 14 publications

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“…These enzymes catalyze essential biochemical reactions such as the formation of deoxyribonucleotides and aerobic oxidation of carbohydrates and fatty acids in the mitochondrial citric acid cycle and the respiratory chain. [25][26][27] The results of this study are in agreement with previous studies indicating a beneficial effect of oral iron therapy in comparable patient groups. [11][12][13]18 Oral iron treatment, however, can be accompanied by gastrointestinal side effects and usually requires administration over several months because intestinal iron absorption is low 6 ; both of these factors affect patients' adherence to therapy.…”

Section: Discussionsupporting

confidence: 89%

Intravenous iron for the treatment of fatigue in nonanemic, premenopausal women with low serum ferritin concentration

Krayenbuehl

Battegay

Breymann

et al. 2011

Blood

221

197

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This is the first study to investigate the efficacy of intravenous iron in treating fatigue in nonanemic patients with low serum ferritin concentration. In a randomized, double-blinded, placebo-controlled study, 90 premenopausal women presenting with fatigue, serum ferritin < 50 ng/mL, and hemoglobin > 120 g/L were randomized to receive either 800 mg of intravenous iron (III)-hydroxide sucrose or intravenous placebo. Fatigue and serum iron status were assessed at baseline and after 6 and 12 weeks. Median fatigue at baseline was 4.5 (on a 0-10 scale). Fatigue decreased during the initial 6 weeks by 1.1 in the iron group compared with 0.7 in the placebo group (P ‫؍‬ .07). Efficacy of iron was bound to depleted iron stores: In patients with baseline serum ferritin < 15 ng/mL, fatigue decreased by 1.8 in the iron group compared with 0.4 in the placebo group (P ‫؍‬ .005), and 82% of iron-treated compared with 47% of placebo-treated patients reported improved fatigue (P ‫؍‬ .03). Drug-associated adverse events were observed in 21% of iron-treated patients and in 7% of placebo-treated patients (P ‫؍‬ .05); none of these events was serious. Intravenous administration of iron improved fatigue in iron-deficient, nonanemic women with a good safety and tolerability profile. The efficacy of intravenous iron was bound to a serum ferritin concentration < 15 ng/mL. Continuing Medical Education onlineThis activity has been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education through the joint sponsorship of Medscape, LLC and the American Society of Hematology. Medscape, LLC is accredited by the ACCME to provide continuing medical education for physicians. Medscape, LLC designates this Journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. All other clinicians completing this activity will be issued a certificate of participation. To participate in this journal CME activity: (1) review the learning objectives and author disclosures; (2) study the education content; (3) take the post-test with a 70% minimum passing score and complete the evaluation at http://www.medscape.org/journal/blood; and (4) view/print certificate. For CME questions, see page 3450. Disclosures This study was funded by Vifor Pharma (Villars-sur-Glâne, Switzerland). The sponsor of the study was involved in the trial design and was responsible for data collection and storage. The authors had full access to all data and were responsible for the analysis and interpretation of the data presented in this publication. Christian Breymann is a consulting expert for Vifor Pharma in the field of obstetrics and gynecology. The remaining authors, the Associate Editor Martin S. Tallman, and the CME questions author Laurie Barclay, freelance writer and reviewer, Medscape, LLC, declare no competing financial interests. Learning objectives Upon completion of th...

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Section: Discussionsupporting

confidence: 89%

Intravenous iron for the treatment of fatigue in nonanemic, premenopausal women with low serum ferritin concentration

Krayenbuehl

Battegay

Breymann

et al. 2011

Blood

221

197

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“…measured by rates of phosphorylation with pyruvate-malate, succinate and a-glycerophosphate as substrate. The results are in accord with findings in our previous studies on preparations from unseparated pooled muscle (1, 2, 4,6) and with the more recent reports of other workers (1 1, 13,14,15). These results suggest strongly that iron deficiency results in defective oxidative energy metabolism in red and intermediate skeletal muscle with greatly decreased production of ATP, and decreased activity of the a-glycerophosphate shuttle which is necessary for the conversion of cytoplasmic NADH to NAD and continued operation of glycolysis.…”

Section: Resultssupporting

confidence: 93%

Iron Deficiency in the Rat: Effects of Oxidative Metabolism in Distinct Types of Skeletal Muscle

Mackler¹,

Grace²,

Finch³

1984

Pediatr Res

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SummaryStudies performed on iron-deficient and control rats demonstrated that oxidative energy production (phosphorylation) by mitochondria from iron-deficient red and intermediate skeletal muscles was greatly reduced with pyruvate-malate, succinate, and a-glycerophosphate as substrates. Although phosphorylation was also decreased in iron-deficient white skeletal muscle with succinate and pyruvate-malate as substrates, no change was found with a-glycerophosphate as substrate.

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“…2). Improved iron status may increase skeletal muscle capacity for aerobic metabolism (37,38). In line with this, the level of skeletal muscle myoglobin, a heme-carrying protein, transporting oxygen to the mitochondria, was non-significantly increased in TgPrkag3 225Q mice, as determined by Western blot analysis (data not shown).…”

Section: Possible Role For the Ampk ␥3-subunit In The Regulation Of Cmentioning

confidence: 60%

Opposite Transcriptional Regulation in Skeletal Muscle of AMP-activated Protein Kinase γ3 R225Q Transgenic Versus Knock-out Mice

Nilsson¹,

Long

Martinsson³

et al. 2006

Journal of Biological Chemistry

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AMP-activated protein kinase (AMPK) is an evolutionarily conserved heterotrimer important for metabolic sensing in all eukaryotes. The muscle-specific isoform of the regulatory ␥-subunit of the kinase, AMPK ␥3, has an important role in glucose uptake, glycogen synthesis, and fat oxidation in white skeletal muscle, as previously demonstrated by physiological characterization of AMPK ␥3 mutant (R225Q) transgenic (TgPrkag3 225Q ) and ␥3 knock-out (Prkag3 ؊/؊ ) mice. We determined AMPK ␥3-dependent regulation of gene expression by analyzing global transcription profiles in glycolytic skeletal muscle from ␥3 mutant transgenic and knock-out mice using oligonucleotide microarray technology. Evidence is provided for coordinated and reciprocal regulation of multiple key components in glucose and fat metabolism, as well as skeletal muscle ergogenics in TgPrkag3 225Q and Prkag3 ؊/؊ mice. The differential gene expression profile was consistent with the physiological differences between the models, providing a molecular mechanism for the observed phenotype. The striking pattern of opposing transcriptional changes between TgPrkag3 225Q and Prkag3 ؊/؊ mice identifies differentially expressed targets being truly regulated by AMPK and is consistent with the view that R225Q is an activating mutation, in terms of its downstream effects. Additionally, we identified a wide array of novel targets and regulatory pathways for AMPK in skeletal muscle.AMP-activated protein kinase (AMPK) 2 is a critical regulator of carbohydrate and fat metabolism in eukaryotic cells (reviewed in Refs. 1 and 2). AMPK is a heterotrimer that consists of ␣-, ␤-, and ␥-subunits, all of which are required for its activity. The catalytic ␣-subunit contains a conventional serine/threonine protein kinase domain, and phosphorylation of Thr-172 residue within the activation loop of the ␣-subunit by upstream kinases is essential for the activity of the heterotrimer (3-6). Once phosphorylated at Thr-172, AMPK can be further activated by allosteric binding of AMP to the evolutionary conserved cystathionine ␤-synthase domains in the regulatory ␥-subunit (7). The AMPK ␤-subunit acts as a scaffold for binding of the ␣-and ␥-subunits (8). The ␤-subunit also contains a glycogen-binding domain, and recent findings provide evidence that this motif is involved in targeting the AMPK complex to cellular glycogen stores (9, 10). The mammalian genome contains seven AMPK genes encoding for two ␣-, two ␤-, and three ␥-isoforms. Thus, there are 12 possible combinations of heterotrimeric AMPK, and the physiological function of the AMPK holoenzyme depends on the particular isoforms present in the complex.We have provided evidence that AMPK ␥3 is the predominant ␥-isoform expressed in glycolytic (white, fast-twitch type II) skeletal muscle (11). In contrast, it is expressed at low levels in oxidative (red, slowtwitch type I) skeletal muscle and is undetectable in brain, liver, heart, or white adipose tissue (11). Thus, the AMPK ␥3-subunit is the only isoform exhibiting tissue-specific ...

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Physiological and biochemical effects of iron deficiency on rat skeletal muscle

Cited by 112 publications

References 14 publications

Intravenous iron for the treatment of fatigue in nonanemic, premenopausal women with low serum ferritin concentration

Intravenous iron for the treatment of fatigue in nonanemic, premenopausal women with low serum ferritin concentration

Iron Deficiency in the Rat: Effects of Oxidative Metabolism in Distinct Types of Skeletal Muscle

Opposite Transcriptional Regulation in Skeletal Muscle of AMP-activated Protein Kinase γ3 R225Q Transgenic Versus Knock-out Mice

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