scholarly journals Motoneuron-derived Activinβ regulates Drosophila body size and tissue-scaling during larval growth and adult development

2019 ◽  
Author(s):  
Lindsay Moss-Taylor ◽  
Ambuj Upadhyay ◽  
Xueyang Pan ◽  
Myung-Jun Kim ◽  
Michael B. O’Connor
Keyword(s):  
Body Size ◽  
Muscle Mass ◽  
Adult Development ◽  
Fat Body ◽  
Larval Growth ◽  
Muscle Size ◽  
Loss Of Function ◽  
Final Size ◽  
Insect Muscle ◽  
Genetic And Environmental Factors

AbstractCorrect scaling of body and organ size is crucial for proper development and survival of all organisms. Perturbations in circulating hormones, including insulins and steroids, are largely responsible for changing body size in response to both genetic and environmental factors. Such perturbations typically produce adults whose organs and appendages scale proportionately with final size. The identity of additional factors that might contribute to scaling of organs and appendages with body size is unknown. Here we report that loss-of-function mutations in Drosophila Activinβ (Actβ), a member of the TGF-β superfamily, lead to production of small larvae/pupae and undersized rare adult escapers. Morphometric measurements of escaper adult appendage size (wings, legs), as well as heads, thoraxes, and abdomens, reveal a disproportional reduction in abdominal size compared to other tissues. Similar size measurements of selected Actβ mutant larval tissues demonstrate that somatic muscle size is disproportionately smaller when compared to fat body, salivary glands, prothoracic glands, imaginal discs and brain. We also show that Actβ control of body size is dependent on canonical signaling through the transcription-factor dSmad2 and that it modulates the growth rate, but not feeding behavior, during the third instar period. Tissue and cell-specific knockdown and overexpression studies reveal that motoneuron derived Actβ is essential for regulating proper body size and tissue scaling. These studies suggest that, unlike in vertebrates where Myostatin, and certain other Activin-like factors act as systemic negative regulators of muscle mass, in Drosophila Actβ is a positive regulator of muscle mass that is directly delivered to muscles by motoneurons. We discuss the importance of these findings in coordinating proportional scaling of insect muscle mass to appendage size.

scholarly journals Body Size and Tissue-Scaling Is Regulated by Motoneuron-Derived Activinß in Drosophila melanogaster

Genetics ◽  
2019 ◽  
Vol 213 (4) ◽  
pp. 1447-1464 ◽  
Author(s):  
Lindsay Moss-Taylor ◽  
Ambuj Upadhyay ◽  
Xueyang Pan ◽  
Myung-Jun Kim ◽  
Michael B. O’Connor
Keyword(s):  
Body Size ◽  
Muscle Mass ◽  
Fat Body ◽  
Muscle Size ◽  
Loss Of Function ◽  
Final Size ◽  
Somatic Muscle ◽  
Insect Muscle ◽  
Prothoracic Glands ◽  
Genetic And Environmental Factors

Correct scaling of body and organ size is crucial for proper development, and the survival of all organisms. Perturbations in circulating hormones, including insulins and steroids, are largely responsible for changing body size in response to both genetic and environmental factors. Such perturbations typically produce adults whose organs and appendages scale proportionately with final size. The identity of additional factors that might contribute to scaling of organs and appendages with body size is unknown. Here, we report that loss-of-function mutations in DrosophilaActivinβ (Actβ), a member of the TGF-β superfamily, lead to the production of small larvae/pupae and undersized rare adult escapers. Morphometric measurements of escaper adult appendage size (wings and legs), as well as heads, thoraxes, and abdomens, reveal a disproportional reduction in abdominal size compared to other tissues. Similar size measurements of selected Actβ mutant larval tissues demonstrate that somatic muscle size is disproportionately smaller when compared to the fat body, salivary glands, prothoracic glands, imaginal discs, and brain. We also show that Actβ control of body size is dependent on canonical signaling through the transcription-factor dSmad2 and that it modulates the growth rate, but not feeding behavior, during the third-instar period. Tissue- and cell-specific knockdown, and overexpression studies, reveal that motoneuron-derived Actβ is essential for regulating proper body size and tissue scaling. These studies suggest that, unlike in vertebrates, where Myostatin and certain other Activin-like factors act as systemic negative regulators of muscle mass, in Drosophila, Actβ is a positive regulator of muscle mass that is directly delivered to muscles by motoneurons. We discuss the importance of these findings in coordinating proportional scaling of insect muscle mass to appendage size.

scholarly journals The Orphan Nuclear Receptor Nur77 Is a Determinant of Myofiber Size and Muscle Mass in Mice

2015 ◽  
Vol 35 (7) ◽  
pp. 1125-1138 ◽  
Author(s):  
Peter Tontonoz ◽  
Omar Cortez-Toledo ◽  
Kevin Wroblewski ◽  
Cynthia Hong ◽  
Laura Lim ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Mass ◽  
Nuclear Receptor ◽  
Muscle Growth ◽  
Muscle Size ◽  
Orphan Nuclear Receptor ◽  
Loss Of Function ◽  
Transgenic Expression ◽  
Primary Myoblasts ◽  
A Cell

We previously showed that the orphan nuclear receptor Nur77 (Nr4a1) plays an important role in the regulation of glucose homeostasis and oxidative metabolism in skeletal muscle. Here, we show using both gain- and loss-of-function models that Nur77 is also a regulator of muscle growth in mice. Transgenic expression of Nur77 in skeletal muscle in mice led to increases in myofiber size. Conversely, mice with global or muscle-specific deficiency in Nur77 exhibited reduced muscle mass and myofiber size. In contrast to Nur77 deficiency, deletion of the highly related nuclear receptor NOR1 (Nr4a3) had minimal effect on muscle mass and myofiber size. We further show that Nur77 mediates its effects on muscle size by orchestrating transcriptional programs that favor muscle growth, including the induction of insulin-like growth factor 1 (IGF1), as well as concomitant downregulation of growth-inhibitory genes, including myostatin, Fbxo32 (MAFbx), and Trim63 (MuRF1). Nur77-mediated increase in IGF1 led to activation of the Akt-mTOR-S6K cascade and the inhibition of FoxO3a activity. The dependence of Nur77 on IGF1 was recapitulated in primary myoblasts, establishing this as a cell-autonomous effect. Collectively, our findings identify Nur77 as a novel regulator of myofiber size and a potential transcriptional link between cellular metabolism and muscle growth.

scholarly journals Growth regulation by amino acid transporters in Drosophila larvae

2020 ◽  
Vol 77 (21) ◽  
pp. 4289-4297 ◽  
Author(s):  
Gérard Manière ◽  
Georges Alves ◽  
Martine Berthelot-Grosjean ◽  
Yael Grosjean
Keyword(s):  
Amino Acids ◽  
Body Size ◽  
Amino Acid ◽  
Growth Regulation ◽  
Fat Body ◽  
Larval Growth ◽  
Amino Acid Transporters ◽  
Adult Size ◽  
Molecular Signaling ◽  
The Brain

Abstract Drosophila larvae need to adapt their metabolism to reach a critical body size to pupate. This process needs food resources and has to be tightly adjusted to control metamorphosis timing and adult size. Nutrients such as amino acids either directly present in the food or obtained via protein digestion play key regulatory roles in controlling metabolism and growth. Amino acids act especially on two organs, the fat body and the brain, to control larval growth, body size developmental timing and pupariation. The expression of specific amino acid transporters in fat body cells, and in the brain through specific neurons and glial cells is essential to activate downstream molecular signaling pathways in response to amino acid levels. In this review, we highlight some of these specific networks dependent on amino acid diet to control DILP levels, and by consequence larval metabolism and growth.

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.

scholarly journals Association between vitamin D deficiency and exercise capacity in patients with CKD, a cross-sectional analysis

2020 ◽  
Author(s):  
Emma L Watson ◽  
Thomas J Wilkinson ◽  
Tom F O’Sullivan ◽  
Luke A Baker ◽  
Douglas W Gould ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Vitamin D ◽  
Vitamin D Deficiency ◽  
Exercise Capacity ◽  
Muscle Mass ◽  
Ex Vivo ◽  
Muscle Size ◽  
Cross Sectional ◽  
Cross Sectional Analysis ◽  
Sectional Analysis

AbstractEvidence is growing for a role of vitamin D in regulating skeletal muscle mass, strength and functional capacity. Given the role the kidneys play in activating total vitamin D, and the high prevalence of vitamin D deficiency in Chronic Kidney Disease (CKD), it is possible that deficiency contributes to the low levels of physical function and muscle mass in these patients. This is a secondary cross-sectional analysis of previously published interventional study, with ex vivo follow up work. 34 CKD patients at stages G3b-5 (eGFR 25.5 ± 8.3ml/min/1.73m2; age 61 ± 12 years) were recruited, with a sub-group (n=20) also donating a muscle biopsy. Vitamin D and associated metabolites were analysed in plasma by liquid chromatography tandem-mass spectroscopy and correlated to a range of physiological tests of muscle size, function, exercise capacity and body composition. The effects of 1α,25(OH)2D3 supplementation on myogenesis and myotube size was investigated in primary skeletal muscle cells from vitamin D deficient donors. In vivo, there was no association between total or active vitamin D and muscle size or strength, but a significant correlation with was seen with the total form. Ex vivo, 1α,25(OH)2D3 supplementation reduced IL-6 mRNA expression, but had no effect upon proliferation, differentiation or myotube diameter. This early preliminary work suggests that vitamin D deficiency is not a prominent factor driving the loss of muscle mass in CKD, but may play a role in reduced exercise capacity.

scholarly journals Variation in growth and instar number in field and laboratory Manduca sexta

2007 ◽  
Vol 274 (1612) ◽  
pp. 977-981 ◽  
Author(s):  
Joel G Kingsolver
Keyword(s):  
North Carolina ◽  
Body Size ◽  
Manduca Sexta ◽  
Growth Rates ◽  
Developmental Plasticity ◽  
Larval Growth ◽  
Physiological Control ◽  
Larval Instars ◽  
Laboratory Colony ◽  
Early Larval Development

The tobacco hornworm Manduca sexta has been an important model system for understanding physiological control of growth, development and metamorphosis of insects for more than half a century. Like all Manduca , M. sexta typically has five larval instars, with developmental commitment to metamorphosis occurring early in the 5th (final) instar. Here we show that M. sexta from a field population in North Carolina (USA) shows substantial intraspecific variation in the number of larval instars when feeding on a modified artificial diet. Individuals with six instars consistently exhibited slower growth rates during early larval development than individuals with five instars. The frequency of individuals with six instars decreased with increased rearing temperature. In contrast, M. sexta from a laboratory colony consistently had five instars, and had more rapid larval growth rates than M. sexta from the field. We identify a threshold body size at the start of the 5th instar that predicts whether an individual will have five (greater than 600 mg) or six instars (less than 600 mg). Variation in field populations in Manduca provides an important resource for understanding physiological control, developmental plasticity and evolution of growth rate, body size and instar number.

The Effects of Aging and Training on Skeletal Muscle

1998 ◽  
Vol 26 (4) ◽  
pp. 598-602 ◽  
Author(s):  
Donald T. Kirkendall ◽  
William E. Garrett
Keyword(s):  
Skeletal Muscle ◽  
Muscle Mass ◽  
Muscle Function ◽  
Cellular Level ◽  
Type I ◽  
Loss Of Function ◽  
Skeletal Muscle Function ◽  
Cross Sectional ◽  
Age Related ◽  
General Slowing

Aging results in a gradual loss of muscle function, and there are predictable age-related alterations in skeletal muscle function. The typical adult will lose muscle mass with age; the loss varies according to sex and the level of muscle activity. At the cellular level, muscles loose both cross-sectional area and fiber numbers, with type II muscle fibers being the most affected by aging. Some denervation of fibers may occur. The combination of these factors leads to an increased percentage of type I fibers in older adults. Metabolically, the glycolytic enzymes seem to be little affected by aging, but the aerobic enzymes appear to decline with age. Aged skeletal muscle produces less force and there is a general “slowing” of the mechanical characteristics of muscle. However, neither reduced muscle demand nor the subsequent loss of function is inevitable with aging. These losses can be minimized or even reversed with training. Endurance training can improve the aerobic capacity of muscle, and resistance training can improve central nervous system recruitment of muscle and increase muscle mass. Therefore, physical activity throughout life is encouraged to prevent much of the age-related impact on skeletal muscle.

scholarly journals Expression Levels of Long Non-Coding RNAs Change in Models of Altered Muscle Activity and Muscle Mass

2020 ◽  
Vol 21 (5) ◽  
pp. 1628 ◽  
Author(s):  
Keisuke Hitachi ◽  
Masashi Nakatani ◽  
Shiori Funasaki ◽  
Ikumi Hijikata ◽  
Mizuki Maekawa ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Mass ◽  
Muscle Atrophy ◽  
Skeletal Muscle Mass ◽  
Muscle Size ◽  
Skeletal Muscle Atrophy ◽  
Myostatin Gene ◽  
Expression Levels ◽  
Non Coding Rnas

Skeletal muscle is a highly plastic organ that is necessary for homeostasis and health of the human body. The size of skeletal muscle changes in response to intrinsic and extrinsic stimuli. Although protein-coding RNAs including myostatin, NF-κβ, and insulin-like growth factor-1 (IGF-1), have pivotal roles in determining the skeletal muscle mass, the role of long non-coding RNAs (lncRNAs) in the regulation of skeletal muscle mass remains to be elucidated. Here, we performed expression profiling of nine skeletal muscle differentiation-related lncRNAs (DRR, DUM1, linc-MD1, linc-YY1, LncMyod, Neat1, Myoparr, Malat1, and SRA) and three genomic imprinting-related lncRNAs (Gtl2, H19, and IG-DMR) in mouse skeletal muscle. The expression levels of these lncRNAs were examined by quantitative RT-PCR in six skeletal muscle atrophy models (denervation, casting, tail suspension, dexamethasone-administration, cancer cachexia, and fasting) and two skeletal muscle hypertrophy models (mechanical overload and deficiency of the myostatin gene). Cluster analyses of these lncRNA expression levels were successfully used to categorize the muscle atrophy models into two sub-groups. In addition, the expression of Gtl2, IG-DMR, and DUM1 was altered along with changes in the skeletal muscle size. The overview of the expression levels of lncRNAs in multiple muscle atrophy and hypertrophy models provides a novel insight into the role of lncRNAs in determining the skeletal muscle mass.

Muscle Strength, Size, and Composition Following 12 Months of Gender-affirming Treatment in Transgender Individuals

2019 ◽  
Vol 105 (3) ◽  
pp. e805-e813 ◽  
Author(s):  
Anna Wiik ◽  
Tommy R Lundberg ◽  
Eric Rullman ◽  
Daniel P Andersson ◽  
Mats Holmberg ◽  
...  
Keyword(s):  
Muscle Mass ◽  
Muscle Function ◽  
Treatment Initiation ◽  
Hormone Replacement ◽  
Knee Extensor ◽  
Muscle Volume ◽  
Muscle Size ◽  
Thigh Muscle ◽  
Cross Sectional ◽  
One Year

Abstract Context As many sports are divided in male/female categories, governing bodies have formed regulations on the eligibility for transgender individuals to compete in these categories. Yet, the magnitude of change in muscle mass and strength with gender-affirming treatment remains insufficiently explored. Objective This study explored the effects of gender-affirming treatment on muscle function, size, and composition during 12 months of therapy. Design, settings, participants In this single-center observational cohort study, untrained transgender women (TW, n = 11) and transgender men (TM, n = 12), approved to start gender-affirming medical interventions, underwent assessments at baseline, 4 weeks after gonadal suppression of endogenous hormones but before hormone replacement, and 4 and 12 months after treatment initiation. Main outcome measures Knee extensor and flexor strength were assessed at all examination time points, and muscle size and radiological density (using magnetic resonance imaging and computed tomography) at baseline and 12 months after treatment initiation. Results Thigh muscle volume increased (15%) in TM, which was paralleled by increased quadriceps cross-sectional area (CSA) (15%) and radiological density (6%). In TW, the corresponding parameters decreased by –5% (muscle volume) and –4% (CSA), while density remained unaltered. The TM increased strength over the assessment period, while the TW generally maintained their strength levels. Conclusions One year of gender-affirming treatment resulted in robust increases in muscle mass and strength in TM, but modest changes in TW. These findings add new knowledge on the magnitude of changes in muscle function, size, and composition with cross-hormone therapy, which could be relevant when evaluating the transgender eligibility rules for athletic competitions.

Fat body morphology, but not body size, changes in forager bees of Scaptotrigona jujuyensis (Apidae: Meliponini) during foraging season

2019 ◽  
Vol 283 ◽  
pp. 142-149
Author(s):  
Gerónimo L. Galvani ◽  
Eduardo M. Soto ◽  
Lilian E. Canavoso ◽  
Beatriz P. Settembrini
Keyword(s):  
Body Size ◽  
Fat Body ◽  
Body Morphology
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