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Curr Opin Clin Nutr Metab Care. 2006 May;9(3):214-9.

Anabolic potential and regulation of the skeletal muscle satellite cell populations.

Scimè A, Rudnicki MA.

Molecular Medicine Program, Ottawa Health Research Institute, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.

PURPOSE OF REVIEW: Satellite cells are required for muscle regeneration to occur properly. An understanding of the mechanisms that increase their number is important for potential therapeutic use in a variety of muscle disorders. RECENT FINDINGS: This article reviews the state of knowledge regarding mechanisms and factors involved in regulating the satellite cell population. An overview of the soluble factors intrinsic to the regulation of the activation, proliferation and differentiation of satellite cells is presented. We also highlight our current knowledge of satellite cell specification that provides a potential basis for increasing satellite cell numbers by manipulating different cell types. Finally, summarizing our current knowledge of satellite cell self-renewal offers insight for possible avenues to increase the supply of satellite cells. SUMMARY: Multiple approaches for increasing the number and activity of satellite cells will lead to treatments for muscular diseases. For example, in muscular dystrophy the exhaustion of satellite cells is the principal cause of death.



Curr Opin Neurol. 2007 Oct;20(5):577-82.

Activating muscle stem cells: therapeutic potential in muscle diseases.

Boldrin L, Morgan JE.

The Dubowitz Neuromuscular Unit, Department of Paediatrics, Imperial College London, Hammersmith Hospital, London, UK.

PURPOSE OF REVIEW: The satellite cell is the principal muscle stem cell. Recent research, however, has highlighted new stem cell sources that, once activated in the muscle tissue, can participate in muscle regeneration. This article reviews the state of research on stem cell populations that have potential for treatment of muscular dystrophies. RECENT FINDINGS: Despite recent findings about the stem cell character of satellite cells and their in-vivo myogenic potential, limitations related to muscle precursor cell transfer therapy have encouraged the investigation of stem cell sources other than satellite cells. Current research is focused on identifying the best stem cell in the endothelial compartment, which is able to be systemically delivered to reach all the muscles and to contribute to widespread muscle regeneration within these muscles. SUMMARY: Current results highlight many possible stem cell sources for stem cell therapy of muscle diseases, and work is ongoing to identify the most effective candidate that is able to robustly regenerate muscle tissue and to functionally repopulate the muscle stem cell compartment.




J Cell Physiol. 2006 Apr;207(1):1-11.

The epigenetic network regulating muscle development and regeneration.

Palacios D, Puri PL.

Laboratory of Gene Expression, Dulbecco Telethon Institute at Fondazione A. Cesalpino. ICBTE, San Raffaele Biomedical Science Park of Rome, Italy.

This review focuses on our current knowledge of the epigenetic changes regulating gene expression at the chromatin and DNA level, independently on the primary DNA sequence, to reprogram the nuclei of muscle precursors during developmental myogenesis and muscle regeneration. These epigenetic marks provide the blueprint by which the extra-cellular cues are interpreted at the nuclear level by the transcription machinery to select the repertoire of tissue-specific genes to be expressed. The reversibility of some of these changes necessarily reflects the dynamic nature of skeletal myogenesis, which entails the progression through two antagonistic processes--proliferation and differentiation. Other epigenetic modifications are instead associated to events conventionally considered as irreversible--e.g. maintenance of lineage commitment and terminal differentiation. However, recent results support the possibility that these events can be reversed, at least upon certain experimental conditions, thereby revealing a dynamic nature of many of the epigenetic modifications underlying skeletal myogenesis. The elucidation of the epigenetic network that regulates transcription during developmental myogenesis and muscle regeneration might provide the information instrumental to devise pharmacological interventions toward selective manipulation of gene expression to promote regeneration of skeletal muscles and possibly other tissue.


Biochim Biophys Acta. 2006 Aug;1763(8):773-8.

FGF6 in myogenesis.

Armand AS, Laziz I, Chanoine C.

Hubrecht Laboratory and Interuniversity Cardiology Institute Netherlands, Royal Netherlands Academy of Sciences, Utrecht, The Netherlands.

Important functions in myogenesis have been proposed for FGF6, a member of the fibroblast growth factor family accumulating almost exclusively in the myogenic lineage. However, the analyses of Fgf6 (-/-) mutant mice gave contradictory results and the role of FGF6 during myogenesis remained largely unclear. Recent reports support the concept that FGF6 has a dual function in muscle regeneration, stimulating myoblast proliferation/migration and muscle differentiation/hypertrophy in a dose-dependent manner. The alternative use of distinct signaling pathways recruiting either FGFR1 or FGFR4 might explain the dual role of FGF6 in myogenesis. A role for FGF6 in the maintenance of a reserve pool of progenitor cells in the skeletal muscle has been also strongly suggested. The aim of this review is to summarize our knowledge on the involvement of FGF6 in myogenesis.


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Related:



I would imagine this is going to respark the "do we need inflammation for hypertrophy" discussions.

i would think hypertophic muscle growth and myogensis are going to be very different.

I doubt oswaldo cares about finding a cure for muscular dystrophy. I think he was getting at different modes to create more muscles. Realted to past discussions of myostatin downreguation.

Either way, hypertrophy for someone with MD would be useless.

http://www.the-aps.org/press/conference/ibe/5.htm



This speculation, taken in combination with the abstract I posted, could help explain why fat people become muscular despite being sedentary.

Edit: I guess I'm reaching a bit and ASSuming that if IL-6 deficiency "abrogate[s] satellite cell proliferation and myonuclear accretion" then IL-6 surplus would not only normalize this condition but cause the opposite.

There is an excellent discussion in the September issue of the Journal of Applied Physiology titled: Point:Counterpoint: Satellite cell addition is/is not obligatory for skeletal muscle hypertrophy.

I'll upload them later tonight

i think your both missing the point. We aren't looking at hypertrophy here. We're looking for hyperplasia

Horm Res. 2007;67 Suppl 1:64-70.

How proinflammatory cytokines may impair growth and cause muscle wasting.

Thissen JP.


Background: Cytokines, such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-6, that are released in response to injury are thought to inhibit growth and cause muscle wasting, at least in part by inhibiting anabolic hormones such as insulin-like growth factor I (IGF-I). Because critical illness in humans is accompanied by high circulating concentrations of growth hormone (GH), which is the main stimulus for IGF-I production by the liver, resistance to GH is thought to contribute to the IGF-I decline observed in catabolic diseases. While TNF-alpha seems to cause GH resistance mainly through downregulation of liver GH receptor expression, IL-6 may inhibit the GH-stimulated Janus kinase and signal transducer and activator of transcription pathways by induction of suppressors of cytokine signaling proteins. Elevations in circulating IGF binding protein-1 levels, as observed in many catabolic situations, may play a role in the decline in muscle mass by decreasing the rate of protein synthesis in skeletal muscle. Furthermore, the increase in local muscle cytokines produced during inflammation makes the muscle GH-resistant and reduces its own IGF-I production. Finally, not only decreased IGF-I production by muscle, but also decreased muscle sensitivity to the anabolic effects of IGF-I, may contribute to muscle wasting observed in response to severe stress. Conclusions: Taken together, proinflammatory cytokines may contribute to the growth retardation and muscle wasting that occur after injury by impairing the GH/IGF-I axis at several levels.



Endocrinology. 2001 Jan;142(1):241-8.

Interleukin-6 stimulates hepatic insulin-like growth factor binding protein-4 messenger ribonucleic acid and protein.

Fernández-Celemín L, Thissen JP.

Unité de Diabétologie et Nutrition, Université Catholique de Louvain, 54 B-1200 Brussels, Belgium.

....................Sepsis and bacterial lipopolysaccharide (LPS) injection decrease circulating concentrations of insulin-like growth factor (IGF)-I and induce an increase in IGFBP-1 and IGFBP-4 that may have impact upon IGF-I anabolic actions. Although the mechanisms responsible for the IGFBP-1 increase in response to LPS have already been unraveled, the cause for the IGFBP-4 elevation is still unknown. The aim of this study was to characterize the regulation of IGFBP-4 by proinflammatory cytokines and glucocorticoids. In rat primary cultured hepatocytes, interleukin (IL)-6 strongly stimulated IGFBP-4 messenger RNA (mRNA) and protein levels in a dose- and time-dependent way (mRNA levels: 9-fold, P: < 0.01 and protein levels: approximately 3-fold at 24 h, with IL-6 10 ng/ml). ...................................
(corticosteroid muscle catabolism) In contrast, dexamethasone induced IGFBP-4 mRNA and protein and potentiated the effect of IL-6 on IGFBP-4 mRNA (2.5-fold, P: < 0.01 vs. IL-6 alone). Both actinomycin and cycloheximide prevented the IL-6 induction of IGFBP-4 mRNA suggesting that the IL-6 effect on IGFBP-4 gene occurs probably at the transcriptional level and needs an ongoing protein synthesis. Administration of IL-6 to rats caused a 3-fold increase in liver IGFBP-4 mRNA (P: < 0.001) reflected in serum levels of IGFBP-4 (P: < 0.05). In conclusion, our results show that IL-6 stimulates hepatic IGFBP-4 gene expression and production in vitro and in vivo, thereby suggesting another mechanism by which cytokines could control IGF-I action.......................


more, not always it is better.



and.........................


J Appl Physiol. 2005 Mar;98(3):911-7.

IL-6-induced skeletal muscle atrophy.

Haddad F, Zaldivar F, Cooper DM, Adams GR.

Department of Physiology & Biophysics, University of California, Irvine, Medical Sciences 1, Irvine, CA 92697-4560, USA.

Chronic, low-level elevation of circulating interleukin (IL)-6 is observed in disease states as well as in many outwardly healthy elderly individuals. Increased plasma IL-6 is also observed after intense, prolonged exercise. In the context of skeletal muscle, IL-6 has variously been reported to regulate carbohydrate and lipid metabolism, increase satellite cell proliferation, or cause muscle wasting. In the present study, we used a rodent local infusion model to deliver modest levels of IL-6, comparable to that present after exercise or with chronic low-level inflammation in the elderly, directly into a single target muscle in vivo. The aim of this study was to examine the direct effects of IL-6 on skeletal muscle in the absence of systemic changes in this cytokine. Data included cellular and molecular markers of cytokine and growth factor signaling (phosphorylation and mRNA content) as well as measurements to detect muscle atrophy. IL-6 infusion resulted in muscle atrophy characterized by a preferential loss of myofibrillar protein (-17%). IL-6 induced a decrease in the phosphorylation of ribosomal S6 kinase (-60%) and STAT5 (-33%), whereas that of STAT3 was increased approximately twofold. The changes seen in the IL-6-infused muscles suggest alterations in the balance of growth factor-related signaling in favor of a more catabolic profile. This suggests that downregulation of growth factor-mediated intracellular signaling may be a mechanism contributing to the development of muscle atrophy induced by elevated IL-6.







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doesnt IL-6 cause neural pathway inhibition and a decrease in mental acuity? could have sworn i read that years ago when i was trying to come to terms with getting dumber with age...

right.

Int J Geriatr Psychiatry. 2007 Apr;22(4):305-11.

High interleukin-6 plasma levels are associated with functional impairment in older patients with vascular dementia.

Zuliani G, Guerra G, Ranzini M, Rossi L, Munari MR, Zurlo A, Blè A, Volpato S, Atti AR, Fellin R.

Department of Clinical and Experimental Medicine, Section of Internal Medicine, Gerontology and Geriatrics, University of Ferrara, Italy. gzuli

In older individuals, inflammatory mechanisms have been linked to the pathogenesis of both dementia and functional impairment. In this cross-sectional study we have investigated the possible association between some markers of systemic inflammation and functional status, in a sample of one hundred and forty older demented patients including 60 patients with late onset Alzheimer's disease (LOAD) and 80 with vascular dementia (VD). Functional status was evaluated by Barthel Index (BI); the total score ranged from 0 (total dependency) to 20 (total autonomy). Interleukin-1beta, Tumor Necrosis Factor-alpha, Interleukin- 6, Interleukin- 8, and Transforming Grow Factor beta were quantified by ELISA. Among the cytokines evaluated, only IL-6 was correlated with the BI (r: -0.32, p < 0.001). The mean levels of IL-6 progressively decreased from I (9.50 pg/mL), to II (6.40 pg/mL), to III BI tertile (4.80 pg/mL) (p < 0.02). At multiple regression analysis, IL-6 was associated with BI in the whole sample and in VD, but not in LOAD, independent of age, gender, smoking, alcohol consumption, hypertension, diabetes, coronary heart disease, previous stroke, and mini mental state examination score. Our study suggests the existence of an independent and negative relationship between IL-6 plasma levels and functional status in older individuals with vascular dementia. This finding might contribute to explain the 'excess of disability' phenomenon described in older demented patients.


J Neuroimmunol. 2003 Jun;139(1-2):51-7.

Interleukin-6, beta-amyloid peptide and NMDA interactions in rat cortical neurons.

Qiu Z, Gruol DL.

Department of Neuropharmacology, CVN11, The Scripps Research Institute, 10666 N. Torrey Pine Road, La Jolla, CA 92037, USA.

Neuronal damage in Alzheimer's disease (AD) is thought to involve direct toxicity of beta-amyloid peptide (Abeta) and excitotoxicity involving NMDA receptors (NMDARs) and altered Ca(2+) dynamics. Inflammation agents produced by microglia or astrocytes and associated with senile plaques such as the cytokine interleukin-6 (IL-6) could also contribute. To investigate this possibility, neuronal damage (lactate dehydrogenase assay, LDH, assay) was measured in cultures of rodent cortical neurons chronically treated with IL-6, Abeta or Abeta plus IL-6 and acutely treated with NMDA. Both Abeta and NMDA produced neuronal damage and this effect was larger with combined treatment. IL-6 did not produce significant neuronal damage but the largest neuronal damage was observed in cultures exposed to all three factors. IL-6 and Abeta enhanced Ca(2+) responses to NMDA and combined treatment produced the largest effect. These results are consistent with a role for interactions between Abeta, NMDA and IL-6 in the neuronal loss in AD.


Exp Cell Res. 2004 Apr 15;295(1):245-57

Interleukin-6 induces Alzheimer-type phosphorylation of tau protein by deregulating the cdk5/p35 pathway.

Quintanilla RA, Orellana DI, González-Billault C, Maccioni RB.

Millennium Institute for Advanced Studies in Cell Biology and Biotechnology (CBB), Nuñoa, Santiago, Chile.

Inflammation is a process that has been actively related with the onset of several neurodegenerative disorders including Alzheimer disease (AD). However, the precise implications of inflammatory response for neurodegeneration have not been elucidated. A current hypothesis considers that extracellular insults to neurons could trigger the production of inflammatory cytokines by astrocytes and microglia. These cytokines, namely, interleukin (IL)-1beta, TNFalpha, and IL-6, could affect the normal behavior of neuronal cells. In the present study, we describe the effect of the administration at physiologic doses of one of these cytokines, IL-6, to hippocampal neurons, on the protein kinase pathways as well as on the tau phosphorylation patterns. IL-6-treated neurons exhibited an increase in the amount of anomalously hyperphosphorylated tau protein in epitopes dependent on proline-directed protein kinases (PDPKs). On the basis of our data, the observed increase of tau epitopes of Alzheimer type is explained by an increase of intraneuronal levels of p35 activator and in the activity of the protein kinase cdk5 in response to this cytokine. Further confirmation of cdk5 involvement in this process was based on the findings that inhibition of the kinase activity with butyrolactone-I prevents the appearance of tau of Alzheimer type in IL-6-treated neurons. Additional studies suggest that an increase of cdk5 activity could be mediated by a known signaling cascade described for IL-6 function, namely, the MAPK-p38 signaling pathway. Stimulation of the IL-6 pathway appears to increase the tau epitopes of Alzheimer type, as demonstrated in studies with specific inhibitors. These results support the findings of a pathologic role for IL-6 in the neuroinflammatory response as related with the pathogenesis of neuronal degeneration.




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I feel dumber after weight workouts. Mental acuity definitely drops for me.

lol...it might just be a bloodflow/nitrogen issue.

can you explain that a bit more?

just a shot in the dark, really. perhaps some vasoconstriction due to the load bearing, perhaps poor breathing leading to reduction in circulatory efficacy, perhaps increased nitrogen loads on muscle causing an altered distribution that doesnt favor the brain...i dunno. there are so many factors involved.

Could just be endorphins that are raised following exercise, or just simply cortisol levels are higher. Cortisol surpirsingly affects mood.

In regards to the rest of the thread.....
So if elevated IL-6 is cause for muscle atrophy and catabolism, How do we safely keep IL-6 levels in control?
Are there recommended supps or diet? Or is it mostly genetically determined?
Can you routinely test IL-6 in a typical blood chemistry panel, just to see where one stands?

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cos:



then:

Diabetes. 2004 Apr;53(4):1060-7.

Differential effects of interleukin-6 and -10 on skeletal muscle and liver insulin action in vivo.

Kim HJ, Higashimori T, Park SY, Choi H, Dong J, Kim YJ, Noh HL, Cho YR, Cline G, Kim YB, Kim JK.

Department of Internal Medicine, Section of Endocrinology and Metabolism, Yale University School of Medicine, New Haven, Connecticut 06520-8020, USA.

The circulating level of the inflammatory cytokine interleukin (IL)-6 is elevated in various insulin-resistant states including type 2 diabetes, obesity, cancer, and HIV-associated lipodystrophy. To determine the role of IL-6 in the development of insulin resistance, we examined the effects of IL-6 treatment on whole-body insulin action and glucose metabolism in vivo during hyperinsulinemic-euglycemic clamps in awake mice. Pretreatment of IL-6 blunted insulin's ability to suppress hepatic glucose production and insulin-stimulated insulin receptor substrate (IRS)-2-associated phosphatidylinositol (PI) 3-kinase activity in liver. Acute IL-6 treatment also reduced insulin-stimulated glucose uptake in skeletal muscle, and this was associated with defects in insulin-stimulated IRS-1-associated PI 3-kinase activity and increases in fatty acyl-CoA levels in skeletal muscle. In contrast, we found that co-treatment of IL-10, a predominantly anti-inflammatory cytokine, prevented IL-6-induced defects in hepatic insulin action and signaling activity. Additionally, IL-10 co-treatment protected skeletal muscle from IL-6 and lipid-induced defects in insulin action and signaling activity, and these effects were associated with decreases in intramuscular fatty acyl-CoA levels. This is the first study to demonstrate that inflammatory cytokines IL-6 and IL-10 alter hepatic and skeletal muscle insulin action in vivo, and the mechanism may involve cytokine-induced alteration in intracellular fat contents. These findings implicate an important role of inflammatory cytokines in the pathogenesis of insulin resistance.

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Carbs make you dumb...



http://www.future-drugs.com/doi/full/10.15...319?cookieSet=1

os, what I'm getting is that it seems that IL-6 is a good thing as long as it is elevated due to exercise and not injection or existing inflammatory issues.

A note about the difference between us and mice:



http://www.jci.org/articles/view/18526

another with precipated conclusions, i am talking about chronic and systemic il-6 excess.



read yourself again




A decline in S6K1 phosphorylation may indicate that one of the catabolic impacts of elevated IL-6 is a decrease in translational capacity.

http://jap.physiology.org/cgi/content/full/98/3/911



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16750969 pubmed

CONCLUSION: The findings of this prospective, population-based study suggest that higher levels of IL-6 and CRP increase the risk of muscle strength loss

you have to read more yet.....

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