scholarly journals The Price of Surviving on Adrenaline: Developmental Programming Responses to Chronic Fetal Hypercatecholaminemia Contribute to Poor Muscle Growth Capacity and Metabolic Dysfunction in IUGR-Born Offspring

2021 ◽  
Vol 2 ◽  
Author(s):  
Rachel L. Gibbs ◽  
Dustin T. Yates
Keyword(s):  
Muscle Mass ◽  
Muscle Growth ◽  
Growth Efficiency ◽  
Metabolic Dysfunction ◽  
Poor Growth ◽  
Economic Implications ◽  
Growth Capacity ◽  
Thrifty Phenotype ◽  
Fetal Survival ◽  
Adaptive Programing

Maternofetal stress induces fetal programming that restricts skeletal muscle growth capacity and metabolic function, resulting in intrauterine growth restriction (IUGR) of the fetus. This thrifty phenotype aids fetal survival but also yields reduced muscle mass and metabolic dysfunction after birth. Consequently, IUGR-born individuals are at greater lifelong risk for metabolic disorders that reduce quality of life. In livestock, IUGR-born animals exhibit poor growth efficiency and body composition, making these animals more costly and less valuable. Specifically, IUGR-associated programming causes a greater propensity for fat deposition and a reduced capacity for muscle accretion. This, combined with metabolic inefficiency, means that these animals produce less lean meat from greater feed input, require more time on feed to reach market weight, and produce carcasses that are of less quality. Despite the health and economic implications of IUGR pathologies in humans and food animals, knowledge regarding their specific underlying mechanisms is lacking. However, recent data indicate that adaptive programing of adrenergic sensitivity in multiple tissues is a contributing factor in a number of IUGR pathologies including reduced muscle mass, peripheral insulin resistance, and impaired glucose metabolism. This review highlights the findings that support the role for adrenergic programming and how it relates to the lifelong consequences of IUGR, as well as how dysfunctional adrenergic signaling pathways might be effective targets for improving outcomes in IUGR-born offspring.

scholarly journals GDF11 promotes osteogenesis as opposed to MSTN, and follistatin, a MSTN/GDF11 inhibitor, increases muscle mass but weakens bone

2020 ◽  
Vol 117 (9) ◽  
pp. 4910-4920 ◽  
Author(s):  
Joonho Suh ◽  
Na-Kyung Kim ◽  
Seung-Hoon Lee ◽  
Je-Hyun Eom ◽  
Youngkyun Lee ◽  
...  
Keyword(s):  
Bone Mass ◽  
Muscle Mass ◽  
Transforming Growth Factor ◽  
Bone Fractures ◽  
Muscle Growth ◽  
Transforming Growth Factor Β ◽  
Biochemical Properties ◽  
Bmp Signaling ◽  
Morphogenetic Protein ◽  
Perinatal Lethality

Growth and differentiation factor 11 (GDF11) and myostatin (MSTN) are closely related transforming growth factor β (TGF-β) family members, but their biological functions are quite distinct. While MSTN has been widely shown to inhibit muscle growth, GDF11 regulates skeletal patterning and organ development during embryogenesis. Postnatal functions of GDF11, however, remain less clear and controversial. Due to the perinatal lethality ofGdf11null mice, previous studies used recombinant GDF11 protein to prove its postnatal function. However, recombinant GDF11 and MSTN proteins share nearly identical biochemical properties, and most GDF11-binding molecules have also been shown to bind MSTN, generating the possibility that the effects mediated by recombinant GDF11 protein actually reproduce the endogenous functions of MSTN. To clarify the endogenous functions of GDF11, here, we focus on genetic studies and show thatGdf11null mice, despite significantly down-regulatingMstnexpression, exhibit reduced bone mass through impaired osteoblast (OB) and chondrocyte (CH) maturations and increased osteoclastogenesis, while the opposite is observed inMstnnull mice that display enhanced bone mass. Mechanistically,Mstndeletion up-regulatesGdf11expression, which activates bone morphogenetic protein (BMP) signaling pathway to enhance osteogenesis. Also, mice overexpressing follistatin (FST), a MSTN/GDF11 inhibitor, exhibit increased muscle mass accompanied by bone fractures, unlikeMstnnull mice that display increased muscle mass without fractures, indicating that inhibition of GDF11 impairs bone strength. Together, our findings suggest that GDF11 promotes osteogenesis in contrast to MSTN, and these opposing roles of GDF11 and MSTN must be considered to avoid the detrimental effect of GDF11 inhibition when developing MSTN/GDF11 inhibitors for therapeutic purposes.

Muscle growth, cell number, type and morphometry in single and twin fetal lambs during mid to late gestation

2000 ◽  
Vol 12 (6) ◽  
pp. 319 ◽  
Author(s):  
S. A. McCoard ◽  
W. C. McNabb ◽  
S. W. Peterson ◽  
S. N. McCutcheon ◽  
P. M. Harris
Keyword(s):  
Muscle Mass ◽  
Litter Size ◽  
Muscle Growth ◽  
Cell Number ◽  
Late Gestation ◽  
Postnatal Life ◽  
Cross Sectional ◽  
Hindlimb Muscles ◽  
Full Complement ◽  
Gastrocnemius Muscles

Muscle growth, myofibre number, type and morphometry were studied in large hindlimb muscles of single and twin fetal lambs during mid to late gestation. Placental insufficiency, evident by lower total placentome weight and number per fetus, resulted in reduced fetal weights from 100 to 140 days gestation in twins compared with singletons (at 140 days: 5016 108 g v. 5750 246 g, respectively; P<0.05). However, competition between littermates did not consistently reduce muscle mass (15–22%) until 140 days gestation. Apparent myofibre number increased with age, indicating that the full complement of myofibres in some large hindlimb muscles may be achieved during early postnatal life. Litter size did not impact on apparent myofibre number in the semitendinosus, plantaris or gastrocnemius muscles. However, a transient effect on myofibre number in the adductor femoris muscle was observed from 80–120 days gestation. The phenotypic maturation of myofibres was unaffected by increasing litter size. Smaller muscle mass in twins was associated with smaller myofibre cross-sectional area in the semitendinosus, adductor femoris and gastrocnemius muscles at 140 days gestation. A similar trend was observed for the plantaris muscle. These results indicate that while competition between littermates for nutrients in late gestation can impact on both fetal and muscle mass, the fetus has the capacity to buffer against the effects of restricted nutrient supply on myofibre hyperplasia and phenotypic maturation, but myofibre hypertrophy is compromised.

scholarly journals A Systematic Review with Meta-Analysis of the Effect of Resistance Training on Whole-Body Muscle Growth in Healthy Adult Males

2020 ◽  
Vol 17 (4) ◽  
pp. 1285 ◽  
Author(s):  
Pedro J. Benito ◽  
Rocío Cupeiro ◽  
Domingo J. Ramos-Campo ◽  
Pedro E. Alcaraz ◽  
Jacobo Á. Rubio-Arias
Keyword(s):  
Systematic Review ◽  
Resistance Training ◽  
Muscle Mass ◽  
Meta Analysis ◽  
Muscle Growth ◽  
Fat Free Mass ◽  
Muscle Size ◽  
Whole Body ◽  
Cochrane Library ◽  
Significant Variable

We performed a systematic review and meta-analysis to study all published clinical trial interventions, determined the magnitude of whole-body hypertrophy in humans (healthy males) and observed the individual responsibility of each variable in muscle growth after resistance training (RT). Searches were conducted in PubMed, Web of Science and the Cochrane Library from database inception until 10 May 2018 for original articles assessing the effects of RT on muscle size after interventions of more than 2 weeks of duration. Specifically, we obtain the variables fat-free mass (FMM), lean muscle mass (LMM) and skeletal muscle mass (SMM). The effects on outcomes were expressed as mean differences (MD) and a random-effects meta-analysis and meta-regressions determined covariates (age, weight, height, durations in weeks…) to explore the moderate effect related to the participants and characteristics of training. One hundred and eleven studies (158 groups, 1927 participants) reported on the effects of RT for muscle mass. RT significantly increased muscle mass (FFM+LMM+SMM; Δ1.53 kg; 95% CI [1.30, 1.76], p < 0.001; I2 = 0%, p = 1.00). Considering the overall effects of the meta-regression, and taking into account the participants’ characteristics, none of the studied covariates explained any effect on changes in muscle mass. Regarding the training characteristics, the only significant variable that explained the variance of the hypertrophy was the sets per workout, showing a significant negative interaction (MD; estimate: 1.85, 95% CI [1.45, 2.25], p < 0.001; moderator: -0.03 95% CI [−0.05, −0.001] p = 0.04). In conclusion, RT has a significant effect on the improvement of hypertrophy (~1.5 kg). The excessive sets per workout affects negatively the muscle mass gain.

The COX-2 pathway regulates growth of atrophied muscle via multiple mechanisms

2006 ◽  
Vol 290 (6) ◽  
pp. C1651-C1659 ◽  
Author(s):  
Brenda A. Bondesen ◽  
Stephen T. Mills ◽  
Grace K. Pavlath
Keyword(s):  
Muscle Mass ◽  
Muscle Regeneration ◽  
Muscle Growth ◽  
Cell Activity ◽  
Hindlimb Suspension ◽  
Normal Muscle ◽  
Cox 2 ◽  
Proliferation In Vitro

Loss of muscle mass occurs with disease, injury, aging, and inactivity. Restoration of normal muscle mass depends on myofiber growth, the regulation of which is incompletely understood. Cyclooxygenase (COX)-2 is one of two isoforms of COX that catalyzes the synthesis of prostaglandins, paracrine hormones that regulate diverse physiological and pathophysiological processes. Previously, we demonstrated that the COX-2 pathway regulates early stages of myofiber growth during muscle regeneration. However, whether the COX-2 pathway plays a common role in adult myofiber growth or functions specifically during muscle regeneration is unknown. Therefore, we examined the role of COX-2 during myofiber growth following atrophy in mice. Muscle atrophy was induced by hindlimb suspension (HS) for 2 wk, followed by a reloading period, during which mice were treated with either the COX-2-selective inhibitor SC-236 (6 mg·kg−1·day−1) or vehicle. COX-2 protein was expressed and SC-236 attenuated myofiber growth during reloading in both soleus and plantaris muscles. Attenuated myofiber growth in the soleus was associated with both decreased myonuclear addition and decreased inflammation, whereas neither of these processes mediated the effects of SC-236 on plantaris growth. In addition, COX-2−/− satellite cells exhibited impaired activation/proliferation in vitro, suggesting direct regulation of muscle cell activity by COX-2. Together, these data suggest that the COX-2 pathway plays a common regulatory role during various types of muscle growth via multiple mechanisms.

scholarly journals Muscle Hyperplasia in Japanese Quail by Single Amino Acid Deletion in MSTN Propeptide

2020 ◽  
Vol 21 (4) ◽  
pp. 1504 ◽  
Author(s):  
Joonbum Lee ◽  
Dong-Hwan Kim ◽  
Kichoon Lee
Keyword(s):  
Muscle Mass ◽  
Gene Knockout ◽  
Muscle Growth ◽  
Avian Species ◽  
Negative Regulator ◽  
Single Amino Acid ◽  
Heart Weight ◽  
Dependent Manner ◽  
Base Pair Deletion ◽  
Muscle Hyperplasia

Mutation in myostatin (MSTN), a negative regulator of muscle growth in skeletal muscle, resulted in increased muscle mass in mammals and fishes. However, MSTN mutation in avian species has not been reported. The objective of this study was to generate MSTN mutation in quail and investigate the effect of MSTN mutation in avian muscle growth. Recently, a new targeted gene knockout approach for the avian species has been developed using an adenoviral CRISPR/Cas9 system. By injecting the recombinant adenovirus containing CRISPR/Cas9 into the quail blastoderm, potential germline chimeras were generated and offspring with three base-pair deletion in the targeted region of the MSTN gene was identified. This non-frameshift mutation in MSTN resulted in deletion of cysteine 42 in the MSTN propeptide region and homozygous mutant quail showed significantly increased body weight and muscle mass with muscle hyperplasia compared to heterozygous mutant and wild-type quail. In addition, decreased fat pad weight and increased heart weight were observed in MSTN mutant quail in an age- and sex-dependent manner, respectively. Taken together, these data indicate anti-myogenic function of MSTN in the avian species and the importance of cysteine 42 in regulating MSTN function.

scholarly journals PSI-15 Determining the molecular mechanism through which estradiol and trenbolone acetate improve skeletal muscle growth in beef cattle

2019 ◽  
Vol 97 (Supplement_3) ◽  
pp. 293-293
Author(s):  
Caleb C Reichhardt ◽  
Chris A Bidwell ◽  
Aaron Thomas ◽  
Amir Ahmadpour
Keyword(s):  
Skeletal Muscle ◽  
Beef Cattle ◽  
Molecular Mechanism ◽  
Muscle Growth ◽  
Specific Inhibitor ◽  
Growth Efficiency ◽  
The United States ◽  
Trenbolone Acetate ◽  
Skeletal Muscle Growth ◽  
Future Work

Abstract Approximately 90% of beef cattle on feed in the United States receive an anabolic implant during production, which results in increased growth, efficiency, and economic return to producers. However, the molecular mechanism through which these anabolic implants operate to improve skeletal muscle growth remains unknown. The objective of this study was to determine the molecular mechanism through which estradiol (E2) and trenbolone acetate (TBA) improve skeletal muscle growth in beef cattle and to specifically understand whether E2 and/or TBA function by modulating transcription. To address this, bovine satellite cells (BSC) were isolated from three different backgrounded steers and grown in culture. Once cultures reached 75% confluency they were treated with 1% fetal bovine serum (FBS) and 10 nM E2 or 10 nM TBA. In an additional experiment, all previously listed treatments were given in addition to actinomycin D (AD, a non-specific inhibitor of transcription). Treatment with E2 or TBA increased proliferation (P &lt; 0.05) when compared to a 1% FBS control. Furthermore, treatment with E2 or TBA in the presence of AD increased proliferation (P &lt; 0.01) when compared to cultures treated with just AD. These results indicate that TBA and E2 are both capable of increasing proliferation of BSC cultures through non-transcriptional mechanisms. Future work will identify the TBA and E2 signaling pathways that affect muscle growth and don’t involve changes in gene transcription.

scholarly journals Estrogen replacement and skeletal muscle: mechanisms and population health

2013 ◽  
Vol 115 (5) ◽  
pp. 569-578 ◽  
Author(s):  
Peter M. Tiidus ◽  
Dawn A. Lowe ◽  
Marybeth Brown
Keyword(s):  
Skeletal Muscle ◽  
Postmenopausal Women ◽  
Muscle Mass ◽  
Enhanced Recovery ◽  
Rapid Onset ◽  
Metabolic Dysfunction ◽  
Skeletal Muscle Function ◽  
Strong Argument ◽  
Beneficial Effects ◽  
Health Related

There is a growing body of information supporting the beneficial effects of estrogen and estrogen-based hormone therapy (HT) on maintenance and enhancement of muscle mass, strength, and connective tissue. These effects are also evident in enhanced recovery from muscle atrophy or damage and have significant implications particularly for the muscular health of postmenopausal women. Evidence suggests that HT will also help maintain or increase muscle mass, improve postatrophy muscle recovery, and enhance muscle strength in aged females. This is important because this population, in particular, is at risk for a rapid onset of frailty. The potential benefits of estrogen and HT relative to skeletal muscle function and composition combined with other health-related enhancements associated with reduced risk of cardiovascular events, overall mortality, and metabolic dysfunction, as well as enhanced cognition and bone health cumulate in a strong argument for more widespread and prolonged consideration of HT if started proximal to menopausal onset in most women. Earlier reports of increased health risks with HT use in postmenopausal women has led to a decline in HT use. However, recent reevaluation regarding the health effects of HT indicates a general lack of risks and a number of significant health benefits of HT use when initiated at the onset of menopause. Although further research is still needed to fully delineate its mechanisms of action, the general use of HT by postmenopausal women, to enhance muscle mass and strength, as well as overall health, with initiation soon after the onset of menopause should be considered.

scholarly journals Functional redundancy of type I and type II receptors in the regulation of skeletal muscle growth by myostatin and activin A

2020 ◽  
Vol 117 (49) ◽  
pp. 30907-30917 ◽  
Author(s):  
Se-Jin Lee ◽  
Adam Lehar ◽  
Yewei Liu ◽  
Chi Hai Ly ◽  
Quynh-Mai Pham ◽  
...  
Keyword(s):  
Family Member ◽  
Muscle Mass ◽  
Transforming Growth Factor ◽  
Muscle Growth ◽  
Functional Redundancy ◽  
Activin A ◽  
Metabolic Effects ◽  
Type I ◽  
Type Ii

Myostatin (MSTN) is a transforming growth factor-β (TGF-β) family member that normally acts to limit muscle growth. The function of MSTN is partially redundant with that of another TGF-β family member, activin A. MSTN and activin A are capable of signaling through a complex of type II and type I receptors. Here, we investigated the roles of two type II receptors (ACVR2 and ACVR2B) and two type I receptors (ALK4 and ALK5) in the regulation of muscle mass by these ligands by genetically targeting these receptors either alone or in combination specifically in myofibers in mice. We show that targeting signaling in myofibers is sufficient to cause significant increases in muscle mass, showing that myofibers are the direct target for signaling by these ligands in the regulation of muscle growth. Moreover, we show that there is functional redundancy between the two type II receptors as well as between the two type I receptors and that all four type II/type I receptor combinations are utilized in vivo. Targeting signaling specifically in myofibers also led to reductions in overall body fat content and improved glucose metabolism in mice fed either regular chow or a high-fat diet, demonstrating that these metabolic effects are the result of enhanced muscling. We observed no effect, however, on either bone density or muscle regeneration in mice in which signaling was targeted in myofibers. The latter finding implies that MSTN likely signals to other cells, such as satellite cells, in addition to myofibers to regulate muscle homeostasis.

scholarly journals The bone morphogenetic protein axis is a positive regulator of skeletal muscle mass

2013 ◽  
Vol 203 (2) ◽  
pp. 345-357 ◽  
Author(s):  
Catherine E. Winbanks ◽  
Justin L. Chen ◽  
Hongwei Qian ◽  
Yingying Liu ◽  
Bianca C. Bernardo ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Bone Morphogenetic Protein ◽  
Signaling Pathway ◽  
Muscle Mass ◽  
Muscle Wasting ◽  
Muscle Growth ◽  
Bmp Signaling ◽  
Positive Regulator ◽  
Bmp Receptors ◽  
Morphogenetic Protein

Although the canonical transforming growth factor β signaling pathway represses skeletal muscle growth and promotes muscle wasting, a role in muscle for the parallel bone morphogenetic protein (BMP) signaling pathway has not been defined. We report, for the first time, that the BMP pathway is a positive regulator of muscle mass. Increasing the expression of BMP7 or the activity of BMP receptors in muscles induced hypertrophy that was dependent on Smad1/5-mediated activation of mTOR signaling. In agreement, we observed that BMP signaling is augmented in models of muscle growth. Importantly, stimulation of BMP signaling is essential for conservation of muscle mass after disruption of the neuromuscular junction. Inhibiting the phosphorylation of Smad1/5 exacerbated denervation-induced muscle atrophy via an HDAC4-myogenin–dependent process, whereas increased BMP–Smad1/5 activity protected muscles from denervation-induced wasting. Our studies highlight a novel role for the BMP signaling pathway in promoting muscle growth and inhibiting muscle wasting, which may have significant implications for the development of therapeutics for neuromuscular disorders.

scholarly journals Paracrine and endocrine modes of myostatin action

2016 ◽  
Vol 120 (6) ◽  
pp. 592-598 ◽  
Author(s):  
Yun-Sil Lee ◽  
Thanh V. Huynh ◽  
Se-Jin Lee
Keyword(s):  
Skeletal Muscle ◽  
Muscle Mass ◽  
Muscle Growth ◽  
Therapeutic Strategies ◽  
Muscle Loss ◽  
Physiological Control ◽  
Critical Question ◽  
Signaling Molecule ◽  
Active Pool ◽  
Circulating Levels

Myostatin (MSTN) is a secreted signaling molecule that normally acts to limit muscle mass. In adult animals, MSTN is made almost exclusively by skeletal muscle and circulates in the blood. A critical question is whether this circulating MSTN protein can enter the active pool to regulate muscle growth or whether all of the activity of MSTN results from locally produced protein. Here, we addressed this question in mice by using a Cdx2-Cre transgene in conjunction with a conditional Mstn-flox allele to generate mice in which Mstn was targeted in a regionally restricted manner. Specifically, we generated mosaic mice in which MSTN production was eliminated in posteriorly located muscles but not in anteriorly located muscles, resulting in mice in which circulating levels of MSTN were reduced roughly by half. Analysis of posteriorly located vs. anteriorly located muscles of these mice revealed clear differential effects indicative of an important paracrine role for MSTN in regulating muscle mass. Significant, albeit more subtle, effects consistent with an endocrine mode of MSTN action were also seen in these mice. These findings have important implications not only for the understanding of the physiological control of muscle mass but also for therapeutic strategies to target MSTN to treat patients with muscle loss.

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