Acute daily psychological stress causes increased atrophic gene expression and myostatin-dependent muscle atrophy

Psychological stress is known to attenuate body size and lean body mass. We tested the effects of 1, 3, or 7 days of two different models of psychological stress, 1 h of daily restraint stress (RS) or daily cage-switching stress (CS), on skeletal muscle size and atrophy-associated gene expression in mice. Thymus weights decreased in both RS and CS mice compared with unstressed controls, suggesting that both models activated the hypothalamic-pituitary-adrenal axis. Body mass was significantly decreased at all time points for both models of stress but was greater for RS than CS. Mass of the tibialis anterior (TA) and soleus (SOL) muscles was significantly decreased after 3 and 7 days of RS, but CS only significantly decreased SOL mass after 7 days. TA mRNA levels of the atrophy-associated genes myostatin (MSTN), atrogin-1, and the phosphatidylinositol 3-kinase inhibitory subunit p85α were all significantly increased relative to unstressed mice after 1 and 3 days of RS, and expression of MSTN and p85α mRNA remained elevated after 7 days of RS. Expression of muscle ring finger 1 was increased after 1 day of RS but returned to baseline at 3 and 7 days of RS. MSTN, atrogin-1, and p85α mRNA levels also significantly increased after 1 and 3 days of CS but atrogen-1 mRNA levels had resolved back to normal levels by 3 days and p85α with 7 days of CS. p21CIP mRNA levels were significantly decreased by 3 days of CS or RS. Finally, body mass was minimally affected, and muscle mass was completely unaffected by 3 days of RS in mice null for the MSTN gene, and MSTN inactivation attenuated the increase in atrogin-1 mRNA levels with 4 days of RS compared with wild-type mice. Together these data suggest that acute daily psychological stress induces atrophic gene expression and loss of muscle mass that appears to be MSTN dependent.

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Regulation of Hepatic Insulin-Like Growth Factor-Binding Protein-1 Gene Expression by Insulin: Central Role for Mammalian Target of Rapamycin Independent of Forkhead Box O Proteins

Endocrinology ◽

10.1210/en.2005-0902 ◽

2006 ◽

Vol 147 (5) ◽

pp. 2383-2391 ◽

Cited By ~ 16

Author(s):

Catherine Mounier ◽

Victor Dumas ◽

Barry I. Posner

Keyword(s):

Gene Expression ◽

Rat Liver ◽

Binding Protein ◽

Mammalian Target Of Rapamycin ◽

Pi3 Kinase ◽

Target Of Rapamycin ◽

Mrna Levels ◽

Phosphatidylinositol 3 Kinase ◽

Insulin Inhibition ◽

Phosphatidylinositol 3

The expression of IGF-binding protein-1 (IGFBP-1) is induced in rat liver by dexamethasone and glucagon and is completely inhibited by 100 nm insulin. Various studies have implicated phosphatidylinositol 3-kinase, protein kinase B (Akt), phosphorylation of the transcription factors forkhead in rhabdomyosarcoma 1 (Foxo1)/Foxo3, and the mammalian target of rapamycin (mTOR) in insulin’s effect. In this study we examined insulin regulation of IGFBP-1 in both subconfluent and confluent hepatocytes. In subconfluent hepatocytes, insulin inhibition of IGFBP-1 mRNA levels was blocked by inhibiting PI3 kinase activation, and there was a corresponding inhibition of Foxo1/Foxo3 phosphorylation. In these same cells, inhibition of the insulin effect by rapamycin occurred in the presence of insulin-induced Foxo1/Foxo3 phosphorylation. In confluent hepatocytes, insulin could not activate the phosphatidylinositol 3-kinase (PI3 kinase)-Akt-Foxo1/Foxo3 pathway, but still inhibited IGFBP-1 gene expression in an mTOR-dependent manner. In subconfluent hepatocytes, the serine/threonine phosphatase inhibitor okadaic acid (100 nm) partially inhibited IGFBP-1 gene expression by 40%, but did not produce phosphorylation of either Akt or Foxo proteins. In contrast, 1 nm insulin inhibited the IGFBP-1 mRNA level by 40% and correspondingly activated Akt and Foxo1/Foxo3 phosphorylation to a level comparable to that observed with 100 nm insulin. These results suggest a potential role for a serine/threonine phosphatase(s) in the regulation of IGFBP-1 gene transcription, which is not downstream of mTOR and is independent of Akt. In conclusion, we have found that in rat liver, insulin inhibition of IGFBP-1 mRNA levels can occur in the absence of the phosphorylation of Foxo1/Foxo3, whereas activation of the mTOR pathway is both necessary and sufficient.

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Muscle expression of genes associated with inflammation, growth, and remodeling is strongly correlated in older adults with resistance training outcomes

Physiological Genomics ◽

10.1152/physiolgenomics.00056.2009 ◽

2009 ◽

Vol 38 (2) ◽

pp. 169-175 ◽

Cited By ~ 31

Author(s):

Richard A. Dennis ◽

Haiyan Zhu ◽

Patrick M. Kortebein ◽

Heather M. Bush ◽

Jonathan F. Harvey ◽

...

Keyword(s):

Gene Expression ◽

Older Adults ◽

Training Program ◽

Acute Exercise ◽

Muscle Size ◽

Thigh Muscle ◽

Matrix Metalloproteinase 2 ◽

Mrna Levels ◽

Strongly Correlated ◽

Training Outcomes

A group ( n = 8) of healthy older (68 ± 6 yr) adults participated in a 36-session progressive resistance exercise training program targeting the thigh muscles to determine the relationship between muscle gene expression and gains in muscle size and strength. Biopsies were obtained from the vastus lateralis at baseline 72 h after an acute bout of exercise and 72 h after completion of the training program. Training increased thigh muscle size (7%) and strength for the three exercises performed: knee extension (30%) and curl (28%) and leg press (20%). We quantified 18 transcripts encoding factors that function in inflammation, growth, and muscle remodeling that were demonstrated previously to be regulated by aging and acute exercise. The gain in extension strength and muscle size showed a high number of significant correlations with gene expression. These gains were most strongly correlated ( P ≤ 0.003, R ≥ 0.89) with the baseline mRNA levels for insulin-like growth factor-1, matrix metalloproteinase-2 and its inhibitor TIMP1, and ciliary neurotrophic factor. Moreover, strength gains were inversely correlated with the change in these mRNA levels after training ( P ≤ 0.002 and R ≤ −0.90). Changes in gene expression after acute exercise were not associated with training outcomes. These results suggest that higher baseline expression for key genes in muscle conveys an adaptive advantage for certain older adults. Individuals with lower baseline expression of these genes show less adaptation to exercise despite increased gene expression in response to training. These genes hold promise as useful predictors of training outcomes that could be used to design more effective exercise regimens for maintaining muscle function in older adults.

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Age-Related Loss of Muscle Mass, Strength, and Power and Their Association With Mobility in Recreationally-Active Older Adults in the United Kingdom

Journal of Aging and Physical Activity ◽

10.1123/japa.2013-0219 ◽

2015 ◽

Vol 23 (3) ◽

pp. 352-360 ◽

Cited By ~ 20

Author(s):

Thomas M. Maden-Wilkinson ◽

Jamie S. McPhee ◽

David A. Jones ◽

Hans Degens

Keyword(s):

Older Adults ◽

Muscle Mass ◽

Body Mass ◽

Functional Performance ◽

Muscle Size ◽

Timed Up And Go ◽

Lower Velocity ◽

The United Kingdom ◽

Age Related ◽

Force Ratio

To investigate reasons for the age-related reduction in physical function, we determined the relationships between muscle size, strength, and power with 6-min walk distance (6MWD) and timed up-and-go performance in 49 young (23 ± 3.1 years) and 66 healthy, mobile older adults (72 ± 5 years). While muscle mass, determined by DXA and MRI, did not correlate with performance in the older adults, power per body mass, determined from a countermovement jump, did correlate. The 40% lower jumping power observed in older adults (p < .05) was due to a lower take-off velocity, which explained 34% and 42% of the variance in 6MWD in older women and men, respectively (p < .01). The lower velocity was partly attributable to the higher body mass to maximal force ratio, but most was due to a lower intrinsic muscle speed. While changes in muscle function explain part of the age-related reduction in functional performance, ~60% of the deficit remains to be explained.

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Corticosterone-induced negative feedback mechanisms within the hypothalamo–pituitary–adrenal axis of the chicken

Journal of Endocrinology ◽

10.1677/joe.1.05969 ◽

2005 ◽

Vol 185 (3) ◽

pp. 383-391 ◽

Cited By ~ 25

Author(s):

Kristien Vandenborne ◽

Bert De Groef ◽

Sofie M E Geelissen ◽

Eduard R Kühn ◽

Veerle M Darras ◽

...

Keyword(s):

Gene Expression ◽

Negative Feedback ◽

Feedback Inhibition ◽

Mrna Levels ◽

Hypothalamic Area ◽

Adrenal Axis ◽

Pomc Mrna ◽

Pituitary Adrenal Axis

This paper reports the results of in vivo and in vitro experiments on the feedback effects of corticosterone on the hypothalamo–pituitary–adrenal axis in embryos at day 18 of incubation and in 9-day-old chickens. In vivo, a significant negative feedback was detected on the levels of corticotropin-releasing factor (CRF) precursor (proCRF) mRNA and on the plasma concentration of corticosterone, two hours after a single intravenous injection with 40 μg corticosterone. In contrast, the levels of CRF peptide in the hypothalamic area, the CRF receptor type 1 (CRF-R1) mRNA and pro-opiomelanocortin (POMC) mRNA levels in the pituitary were not affected by the in vivo administration of corticosterone. In vitro, incubation with 1 μM corticosterone did not affect the CRF-R1 mRNA levels in the pituitary, but significant feedback inhibition was observed on the POMC mRNA levels. These in vitro effects were the same at the two ages studied. The in vitro feedback effect on the proCRF gene expression, however, differed with age. In 9-day-old animals a decrease in gene expression was observed which was not detectable in embryonic tissue at day 18 of the ontogeny.

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Body-building without power training: endogenously regulated pectoral muscle hypertrophy in confined shorebirds

Journal of Experimental Biology ◽

10.1242/jeb.202.20.2831 ◽

1999 ◽

Vol 202 (20) ◽

pp. 2831-2837 ◽

Cited By ~ 15

Author(s):

M.W. Dietz ◽

T. Piersma ◽

A. Dekinga

Keyword(s):

Muscle Mass ◽

Body Mass ◽

Muscle Hypertrophy ◽

Pectoral Muscle ◽

Muscle Size ◽

Power Training ◽

Diet Change ◽

Circannual Rhythm ◽

Migration Patterns ◽

Calidris Canutus

Shorebirds such as red knots Calidris canutus routinely make migratory flights of 3000 km or more. Previous studies on this species, based on compositional analyses, suggest extensive pectoral muscle hypertrophy in addition to fat storage before take-off. Such hypertrophy could be due to power training and/or be effected by an endogenous circannual rhythm. Red knots of two subspecies with contrasting migration patterns were placed in a climate-controlled aviary (12 h:12 h L:D photoperiod) where exercise was limited. Using ultrasonography, we measured pectoral muscle size as the birds stored fat in preparation for migration. At capture, there were no differences in body mass and pectoral muscle mass between the two subspecies. As they prepared for southward and northward migration, respectively, the tropically wintering subspecies (C. c. canutus) gained 31 g and the temperate wintering subspecies (C. c. islandica) gained 41 g. During this time, pectoral mass increased by 43–44 % of initial mass, representing 39 % (C. c. canutus) and 29 % (C. c. islandica) of the increase in body mass. The gizzard showed atrophy in conjunction with a diet change from molluscs to food pellets. Although we cannot exclude the possibility that the birds' limited movement may still be a prerequisite for pectoral muscle hypertrophy, extensive power training is certainly not a requirement. Muscle hypertrophy in the absence of photoperiod cues suggests the involvement of an endogenous circannual process.

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Pretranslational markers of contractile protein expression in human skeletal muscle: effect of limb unloading plus resistance exercise

Journal of Applied Physiology ◽

10.1152/japplphysiol.00553.2004 ◽

2005 ◽

Vol 98 (1) ◽

pp. 46-52 ◽

Cited By ~ 43

Author(s):

F. Haddad ◽

K. M. Baldwin ◽

P. A. Tesch

Keyword(s):

Gene Expression ◽

Skeletal Muscle ◽

Molecular Markers ◽

Resistance Exercise ◽

Myosin Heavy Chain ◽

Muscle Mass ◽

Heavy Chain ◽

Protein Gene ◽

Contractile Protein ◽

Mrna Levels

Previously, it has been shown that the human ground-based model consisting of unilateral limb suspension (ULLS) induces atrophy and reduced strength of the affected quadriceps muscle group. Resistance exercise (RE) involving concentric-eccentric actions, in the face of ULLS, is effective in ameliorating these deficits. The goal of the present study was to determine whether alterations in contractile protein gene expression, e.g., myosin heavy chain and actin, as studied at the pretranslational level, provide molecular markers concerning the deficits that occur in muscle mass/volume during ULLS, as well as its maintenance in response to ULLS plus RE. Muscle biopsies were obtained from the vastus lateralis muscle of 31 middle-aged men and women before and after 5 wk of ULLS, ULLS plus RE, or RE only. The RE paradigm consisted of 12 sessions of 4 sets of 7 concentric-eccentric knee extensions. Our findings show that there were net deficits in total RNA, total mRNA, and actin and myosin heavy chain mRNA levels of expression after ULLS ( P < 0.05), whereas these alterations were blunted in the two groups receiving RE. Additional observations involving IGF-I and its associated receptor and binding proteins suggest that RE postures the skeletal muscle for signaling processes that favor a greater anabolic state relative to that observed in the ULLS group. Collectively, these findings suggest that molecular markers of contractile protein gene expression serve as useful subcellular indicators for ascertaining the underlying mechanisms regulating alterations in muscle mass in human subjects in response to altered loading states.

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IGF-1 does not overcome sexual dimorphism of body and muscle size in Mstn-/- mice

Journal of Endocrinology ◽

10.1530/joe-20-0485 ◽

2020 ◽

Author(s):

Ryan G Paul ◽

Kim Whiteman ◽

Shelley J Falconer ◽

Jenny Oldham ◽

Ferenc Jeanplong ◽

...

Keyword(s):

Skeletal Muscle ◽

Sexual Dimorphism ◽

Muscle Mass ◽

Body Mass ◽

Muscle Size ◽

Sexually Dimorphic ◽

Wild Type ◽

Rapid Phase ◽

Igf1 Receptor ◽

Gastrocnemius Muscles

Insulin-like growth factor-1 (IGF1) is crucial for regulating post-natal growth and, along with myostatin, regulates muscle size. Here, we sought to clarify the roles of these two genes in regulating sexually dimorphic growth of body and muscle mass. In the first study, we established that Igf1 mRNA was increased to a greater extent and Igf1 receptor mRNA increased earlier in male, than in female, gastrocnemius muscles during the rapid phase of growth (2 to 6 weeks), but were unchanged, thereafter, to 32 weeks of age in wild-type mice (P<0.001). In the second study, we sought to determine if supplemental IGF1 could overcome the sexual dimorphism of muscle and body mass, when myostatin is absent. We crossed myostatin null (Mstn-/-) mice with mice over-expressing Igf1 in skeletal muscle (Igf1+) to generate six genotypes; control (Mstn+/+), Mstn+/-, Mstn-/-, Mstn+/+:Igf1+, Mstn+/-:Igf1+ and Mstn-/-:Igf1+ (n=8 per genotype and sex). In both sexes, body mass at 12 weeks was increased by at least 1.6-fold and muscle mass by at least 3-fold in Mstn-/-:Igf1+ compared with Mstn+/+ mice (P<0.001). The abundance of Akt was increased in muscles of mice transgenic for Mstn, while phosphorylation of AktS473 was increased in both male and female mice transgenic for Igf1+. The ratio of phosphorylated to total Akt was 1.9-fold greater in male mice (P<0.001). Thus, despite increased growth of skeletal muscle and body size when myostatin was absent and IGF1 was in excess, sexual dimorphism persisted, an effect consistent with greater IGF1-induced activation of Akt in skeletal muscles of males.

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Avian pectoral muscle size rapidly tracks body mass changes during flight, fasting and fuelling

Journal of Experimental Biology ◽

10.1242/jeb.203.5.913 ◽

2000 ◽

Vol 203 (5) ◽

pp. 913-919 ◽

Cited By ~ 14

Author(s):

A. Lindstrom ◽

A. Kvist ◽

T. Piersma ◽

A. Dekinga ◽

M.W. Dietz

Keyword(s):

Muscle Mass ◽

Body Mass ◽

Muscle Thickness ◽

Pectoral Muscle ◽

The Body ◽

Muscle Size ◽

Migratory Flight ◽

Avian Muscle ◽

Require Power ◽

Body Mass Changes

We used ultrasonic imaging to monitor short-term changes in the pectoral muscle size of captive red knots Calidris canutus. Pectoral muscle thickness changed rapidly and consistently in parallel with body mass changes caused by flight, fasting and fuelling. Four knots flew repeatedly for 10 h periods in a wind tunnel. Over this period, pectoral muscle thickness decreased in parallel with the decrease in body mass. The change in pectoral muscle thickness during flight was indistinguishable from that during periods of natural and experimental fasting and fuelling. The body-mass-related variation in pectoral muscle thickness between and within individuals was not related to the amount of flight, indicating that changes in avian muscle do not require power-training as in mammals. Our study suggests that it is possible for birds to consume and replace their flight muscles on a time scale short enough to allow these muscles to be used as part of the energy supply for migratory flight. The adaptive significance of the changes in pectoral muscle mass cannot be explained by reproductive needs since our knots were in the early winter phase of their annual cycle. Instead, pectoral muscle mass changes may reflect (i) the breakdown of protein during heavy exercise and its subsequent restoration, (ii) the regulation of flight capacity to maintain optimal flight performance when body mass varies, or (iii) the need for a particular protein:fat ratio in winter survival stores.

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Effects of a resistance training community programme in older adults

Ageing and Society ◽

10.1017/s0144686x20001786 ◽

2021 ◽

pp. 1-16

Author(s):

Majid Mufaqam Syed-Abdul ◽

Chrissa L. McClellan ◽

Elizabeth J. Parks ◽

Stephen D. Ball

Keyword(s):

Older Adults ◽

Body Mass Index ◽

Resistance Training ◽

Muscle Mass ◽

Body Mass ◽

Fat Mass ◽

Training Programme ◽

Haemoglobin A1c ◽

Community Based ◽

Resistance Training Programme

Abstract Ageing is associated with reduced muscle mass, strength, flexibility and balance, resulting in a poor quality of life (QOL). Past studies have occurred in highly controlled laboratory settings which provide strong support to determine whether similar gains can be made in community programmes. Twenty participants were enrolled in an eight-week community-based resistance training programme (mean age = 61.3 (standard error (SE) = 0.9) years); Body Mass Index = 32.0 (SE = 1.3) kg/m2). All participants completed surveys to assess outcomes associated with QOL. Given the relationship between muscle function and nerve health, nerve conduction studies (NCS) were also conducted in a separate group of participants (mean age = 64.9 (SE = 2.0) years; Body Mass Index = 32.6 (SE = 1.9) kg/m2). This community-based training programme significantly improved QOL measures in older adults (p < 0.001). Although weight loss was not the primary outcome of the study, participants reduced their body weights (p < 0.001), by primarily reducing fat mass (p = 0.007) while maintaining muscle mass. Significant improvements were observed in muscle strength (2.2%), flexibility and balance (3.2–464.2%, p ⩽ 0.05 for all). Improvements were also observed in plasma glucose (p = 0.05), haemoglobin A1C (p = 0.06) and aldolase enzyme levels (p < 0.001). Scores for surveys on memory and sleep improved (p < 0.05). Improved QOL was associated with increased lean mass (r = −0.714, p = 0.002), decreased fat mass (r = −0.702, p = 0.003) and improved flexibility and balance (r = −0.627, p = 0.008). An eight-week, community-based resistance training programme significantly improved QOL in older adults. Influence on the lipid profile and NCS still needs further investigation.

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The usefulness of competitive PCR: airway gene expression of IL-5, IL-4, IL-4δ2, IL-2, and IFNγ in asthma

Thorax ◽

10.1136/thx.56.7.541 ◽

2001 ◽

Vol 56 (7) ◽

pp. 541-548

Author(s):

E M Glare ◽

M Divjak ◽

M J Bailey ◽

E H Walters

Keyword(s):

Gene Expression ◽

Inhaled Corticosteroids ◽

In Situ Hybridisation ◽

Housekeeping Gene ◽

Cross Sectional Study ◽

Mrna Levels ◽

Competitive Pcr ◽

Cross Sectional ◽

Steroid Use ◽

Biopsy Specimens

BACKGROUNDAsthma has been described as an eosinophilic bronchitis driven by interleukin(IL)-4 and IL-5. The quantification of cytokine mRNA levels in airway samples has been confounded by housekeeping gene expression which differs between and within asthmatics and controls.METHODSThe usefulness of competitive reverse transcriptase-polymerase chain reaction (RT-PCR) that is independent of housekeeping gene expression for quantitating the mRNA for interferon (IFN)γ, IL-2, IL-5, IL-4 and its receptor antagonist encoding splicing variant IL-4δ2 was determined in a cross sectional study of 45 normal control subjects and 111 with asthma.RESULTSAtopic controls and atopic asthmatic subjects expressed more IL-5 than non-atopic controls (p<0.02) in bronchoalveolar lavage (BAL) cells, but not in biopsy specimens. IL-5 mRNA expression in BAL cells from asthmatic subjects using inhaled corticosteroids (ICS) was significantly lower than those not receiving ICS (p=0.04). IL-2 mRNA levels differed with steroid use in biopsy specimens but not in BAL cells. IFNγ, IL-4, and IL-4δ2 mRNA levels did not differ between any groups and were not affected by steroid use. IL-4 and IL-4δ2 mRNA levels were positively correlated (p<0.0001), suggesting coordinated transcription.CONCLUSIONSWhile the signal differentiation of competitive PCR in asthma may rival that of in situ hybridisation and immunohistochemistry, the method is expensive and wasteful of material.

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