scholarly journals Prematurity Alters the Feeding-Induced Activation of Signaling Components Towards AKT in Skeletal Muscle of Neonatal Piglets

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 701-701
Author(s):  
Agus Suryawan ◽  
Marko Rudar ◽  
Jane Naberhuis ◽  
Marta Fiorotto ◽  
Teresa Davis
Keyword(s):  
Skeletal Muscle ◽  
Postnatal Growth ◽  
Milk Composition ◽  
Neonatal Piglets ◽  
Longissimus Dorsi Muscle ◽  
Funding Sources ◽  
Growth Faltering ◽  
Positive Regulators ◽  
Pp2a Activation ◽  
Signaling Components

Abstract Objectives Postnatal growth faltering is a common complication of premature birth. Our recent study in a neonatal pig model of prematurity showed that preterm birth reduces weight gain and protein synthesis in skeletal muscle and this is associated with blunted insulin-induced activation of signaling components downstream of AKT. However, prematurity does not affect the activation of the IR/IRS-1/PI3K axis. In this study, we aimed to identify components in the AKT signaling pathway in skeletal muscle that underlie the differential response to insulin between preterm and term pigs. Methods Cesarean-derived piglets delivered 11 d (preterm) or 2 d (term) before term were fitted with a jugular vein catheter for delivery of total parenteral nutrition. On day 3, all piglets were fasted for 4 h and then assigned randomly to fast one additional h or to receive an elemental meal by oral gavage. Macronutrient content of the elemental meal mimicked sow milk composition at day 3 of lactation. Piglets were euthanized for tissue collection in the fasted state or 60 min after feeding. The longissimus dorsi muscle was collected and subjected to Western blot and immunoprecipitation assays for analyzing upstream regulators of AKT activity. Results Phosphorylation of PDK1 and mTORC2 was lower in preterm than term pigs (P < 0.05). The abundance of phosphatase PHLPP, but not PTEN, was significant higher in preterm than term pigs (P < 0.05). Preterm pigs had lower PP2A activation (P < 0.05), but its activation was not affected by feeding, unlike term pigs where feeding inhibited PP2A activation (P < 0.05). The abundance of Ubl4A, required for insulin-induced translocation of AKT to the plasma membrane, was reduced by prematurity (P < 0.05). While AKT1 abundance was higher in preterm than term pigs (P < 0.05), the abundances of both AKT2 and AKT3 were lower in preterm than term pigs (P < 0.05). Conclusions Our results demonstrate that prematurity reduces the abundance and/or activation of positive regulators of AKT such as Ubl4A, PDK1, and mTORC2. Conversely, prematurity increased the activation of AKT inhibitors such as PHLPP and PP2A. Our findings potentially pave the way for a better understanding of the mechanisms that underlie postnatal growth faltering in premature infants. Funding Sources NIH and USDA.

PSVII-7 Prematurity alters the regulation of Akt signaling in skeletal muscle of piglets

2021 ◽  
Vol 99 (Supplement_3) ◽  
pp. 408-409
Author(s):  
Teresa A Davis ◽  
Agus Suryawan ◽  
Jane Naberhuis ◽  
Marko Rudar ◽  
Marta Fiorotto
Keyword(s):  
Skeletal Muscle ◽  
Preterm Birth ◽  
Premature Birth ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Postnatal Growth ◽  
Receptor Activation ◽  
Skeletal Muscle Protein ◽  
Negative Regulators ◽  
Growth Faltering

Abstract Objectives: Postnatal growth faltering is common after preterm birth. Recently we showed that premature birth in piglets impairs normal postnatal weight gain and skeletal muscle protein synthesis compared to piglets born at term. This response is associated with a reduction in the feeding-induced activation of Akt and subsequent downstream signaling, despite no change in insulin receptor activation. The aim of this study was to identify key regulators of Akt responsible for the blunted anabolic response in preterm muscle. Methods: Piglets delivered by cesarean section 11 d (preterm/PT) or 2 d (term/T) before term birth were fed by total parenteral nutrition. On day 3, after 4 h fasting, piglets were fasted one additional h or fed orally a sow milk replacer (per kg body weight: 31.5 kcal, 1.3 g carbohydrate, 2.7 g amino acids BW, 1.6 g lipid). Positive and negative regulators of Akt activity in longissimus dorsi muscle were determined by Western blot. Results: Phosphorylation of Akt1 and Akt2, but not Akt3, was lower in PT than in T pigs (P < 0.05). Phosphorylation of Akt activators, PDK1 and mTORC2, and the abundance of Ubl4A, a positive regulator of Akt, were lower in PT than in T (P < 0.05). Abundance of Akt inhibitors, PHLPP and SHIP2, but not PTEN, was higher in PT than in T (P < 0.05). Activation of the Akt phosphatase, PP2A, was unaffected by feeding in PT but inhibited by feeding in T pigs (P < 0.05). Conclusions: These results show that the feeding-induced activation of positive regulators of Akt is reduced by preterm birth, whereas the activation of negative regulators is enhanced. Our findings suggest that premature birth impairs the activation of Akt that is essential for channeling dietary nutrients for anabolism and likely contributes to the postnatal growth faltering of prematurity. Research Support: NIH and USDA.

scholarly journals Prematurity blunts the feeding-induced stimulation of translation initiation signaling and protein synthesis in muscle of neonatal piglets

2019 ◽  
Vol 317 (5) ◽  
pp. E839-E851 ◽  
Author(s):  
Jane K. Naberhuis ◽  
Agus Suryawan ◽  
Hanh V. Nguyen ◽  
Adriana Hernandez-Garcia ◽  
Stephanie M. Cruz ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Weight Gain ◽  
Preterm Birth ◽  
Translation Initiation ◽  
Body Weight Gain ◽  
Mammalian Target Of Rapamycin ◽  
Postnatal Growth ◽  
Neonatal Piglets ◽  
Relative Body Weight ◽  
Regulate Protein

Postnatal growth of lean mass is commonly blunted in preterm infants and may contribute to short- and long-term morbidities. To determine whether preterm birth alters the protein anabolic response to feeding, piglets were delivered at term or preterm, and fractional protein synthesis rates (Ks) were measured at 3 days of age while fasted or after an enteral meal. Activation of signaling pathways that regulate protein synthesis and degradation were determined. Relative body weight gain was lower in preterm than in term. Gestational age at birth (GAB) did not alter fasting plasma glucose or insulin, but when fed, plasma insulin and glucose rose more slowly, and reached peak value later, in preterm than in term. Feeding increased Ks in longissimus dorsi (LD) and gastrocnemius muscles, heart, pancreas, and kidney in both GAB groups, but the response was blunted in preterm. In diaphragm, lung, jejunum, and brain, feeding increased Ks regardless of GAB. Liver Ks was greater in preterm than term and increased with feeding regardless of GAB. In all tissues, changes in 4EBP1, S6K1, and PKB phosphorylation paralleled changes in Ks. In LD, eIF4E·eIF4G complex formation, phosphorylation of TSC2, mTOR, and rpS6, and association of mammalian target of rapamycin (mTOR1) complex with RagA, RagC, and Rheb were increased by feeding and blunted by prematurity. There were no differences among groups in LD protein degradation markers. Our results demonstrate that preterm birth reduces weight gain and the protein synthetic response to feeding in muscle, pancreas, and kidney, and this is associated with blunted insulin- and/or amino acid-induced translation initiation signaling.

scholarly journals PSIX-29 JAK2-STAT3 Pathway Mediated Satellite Cell Apoptosis to Govern Skeletal Muscle Growth with Lysine

2020 ◽  
Vol 98 (Supplement_4) ◽  
pp. 334-334
Author(s):  
Zhi-wen Song ◽  
Cheng-long Jin ◽  
Mao Ye ◽  
Chun-qi Gao ◽  
Hui-chao Yan ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Growth ◽  
Longissimus Dorsi ◽  
Control Group ◽  
Stat3 Pathway ◽  
Skeletal Muscle Growth ◽  
Longissimus Dorsi Muscle ◽  
Dorsi Muscle ◽  
Pathway Inhibition ◽  
Induced Apoptosis

Abstract Apoptosis is programmed cell death that can be stimulated by external stress or nutrition restrictions. Lysine (Lys) is an essential amino acid for pig growth, and the relationship between Lys deficiency caused apoptosis and inhibition of skeletal muscle growth remains unknown. The objective of this study was to investigate whether apoptosis could be regulated by Lys supplementation and the potential mechanism. In current work, 30 male Duroc × Landrace × Large weaned piglets were divided randomly into 3 groups: control group (Lys 1.30%), Lys deficiency group (Lys 0.86%), and Lys rescue group (Lys 0.86%, 0-14d; 1.30%,15–28 d). The experiment lasted for 28 days, and on the morning of 29 d, piglets were slaughtered to collect samples. Isobaric tag for relative and absolute quantification (iTRAQ) proteomics analysis of the longissimus dorsi muscle showed that Janus family tyrosine kinase (JAK)-signal transducer and activator of transcription (STAT) pathway was involved in Lys deficiency-induced apoptosis and inhibited skeletal muscle growth. Meanwhile, western blotting results of the longissimus dorsi muscle demonstrated that Lys deficiency caused apoptosis (P < 0.05) with the JAK2-STAT3 pathway inhibition (P < 0.05). Interestingly, apoptosis was suppressed (P < 0.05), and the JAK2-STAT3 pathway was reactivated (P < 0.05) after Lys re-supplementation in longissimus dorsi muscle. In addition, results of satellite cells (SCs) isolated from the longissimus dorsi muscle of 5-day-old Landrace piglets showed that Lys deficiency-induced apoptosis (P < 0.05) was mediated by the JAK2-STAT3 pathway inhibition (P < 0.05). Moreover, the JAK2-STAT3 pathway was reactivated (P < 0.05) by Lys re-supplementation and suppressed apoptosis in SCs (P < 0.05), and this effect was blocked (P < 0.05) after SCs treated with AG-490 (a specific inhibitor of JAK2). Collectively, Lys inhibited apoptosis in SCs to govern skeletal muscle growth via the JAK2-STAT3 pathway.

scholarly journals Paternal High Fat Diet and Exercise Differentially Regulate Placental Development and Inflammation in a Sex-Specific Manner in C57BL6/J Mice (P19-003-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Kate Larson ◽  
Amy Bundy ◽  
Travis Alvine ◽  
James Roemmich
Keyword(s):  
Skeletal Muscle ◽  
Agricultural Research ◽  
Wheel Running ◽  
Fetal Weight ◽  
High Fat ◽  
Placental Development ◽  
Funding Sources ◽  
Service Project ◽  
Diet And Exercise ◽  
Placental Inflammation

Abstract Objectives We have shown that increases in T2D risk in male offspring when the father consumes a high-fat (HF) diet can be normalized when the father also exercises during preconception, and that this protection may occur by epigenetic increases in insulin signaling within offspring skeletal muscle. In our current study, we investigated to determine how paternal HF diet and exercise conditions alter sperm miRNA, fetal weight and placental inflammation. Methods Three-week old male C57BL/6 mice were fed a normal-fat (NF) diet (16% fat) or a HF diet (45% fat) and assigned to either voluntary wheel running exercise or cage activity for 3 months prior to mating with NF diet fed dams. Sperm samples were collected to determine changes in miRNA that may account for the enhanced offspring skeletal muscle responses that helped normalize paternal HF-induced glucose intolerance. Placentae were collected to determine whether changes in sperm miRNA expression differed by amount of placental inflammation. Results Sperm expression of miRNA 193b increased with paternal HF and exercise. In F1 males, placental and fetal weight decreased with HF diet while, in F1 female, paternal HF and exercise had no effect on placental and fetal weights. Paternal HF diet decreased placental IL-6 and TNF-alpha mRNA expression in F1 females, while no effects were observed in F1 male placenta. Conclusions Taken together these data suggest that paternal HF diet has a greater impact on placental development of male fetuses while paternal exercise has greater impact on placental inflammation of female fetuses. For both female and male fetuses, these paternal influences are mediated via sperm miRNA 193b. miR-193b is involved in regulation of the cell cycle and adipogenesis but may have additional functions. Thus, the exact role of sperm miRNA 193b in sex-specific epigenetic transmission of paternal HF diet and exercise on placental and fetal development needs further evaluation. Funding Sources USDA Agricultural Research Service Project #3062-51000-052-00D.

scholarly journals Markers of Metabolism in Skeletal Muscle and White Adipose Tissue are Distinctly Altered by Differing Dietary Oils in ob/ob Mice

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 661-661
Author(s):  
Deena Snoke ◽  
Rachel Cole ◽  
Genevieve Sparagna ◽  
Martha Belury
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Grip Strength ◽  
White Adipose Tissue ◽  
Lipid Storage ◽  
Cross Sectional ◽  
Dietary Oils ◽  
Funding Sources ◽  
The Impact ◽  
Development Center

Abstract Objectives Investigate the impact of LA-rich oil (LO) on measures of energy metabolism in a mouse model of metabolic syndrome. Methods Ob/ob mice were fed diets containing 6% wt LO, oleic acid-rich (OO) or palmitic acid-rich (PO) for 6 weeks. Body composition was measured at weeks 0 and 6. Plasma was collected at necropsy to measure adiponectin, insulin, and glucose. Grip strength and muscle fiber cross-sectional area (CSA) of total and succinate dehydrogenase-positive (SDH) fibers were quantified in quadriceps. In white adipose tissue, mRNA was measured for markers of beiging and lipid storage. Results Mice fed OO and LO diets (vs. PO diet) had reduced % adipose. There was no difference of oils on plasma adiponectin or HOMA-IR. Decreases in grip strength were observed in PO-fed mice, while OO and LO-fed mice maintained strength throughout the study. LO-fed mice exhibited smaller skeletal muscle fibers compared to the PO-fed mice. OO-fed mice had fewer intermediate-sized SDH fibers. In white adipose tissue, LO-fed mice exhibited increased PGC1a, and decreased PPARy and LPL mRNA compared to PO-fed mice. Conclusions These findings suggest that dietary LA may alter lipid mobilization and metabolism in obese mice. These preliminary results showcase the importance of future investigation of lipid storage and mitochondrial phospholipid biology in skeletal muscle. Funding Sources Funding was provided by NIH R21CA185140, Ohio Agriculture Research and Development Center and the Carol S. Kennedy Professorship. DBS received support from the AOCS Thomas H. Smouse Memorial Fellowship.

The relationships of collagen and ADAMTS2 expressionlevels with meat quality traits in cattle

2016 ◽  
Author(s):  
X. H. Zhang ◽  
H. .Liao ◽  
Y. X. Qi ◽  
Y. Q. Wang ◽  
Y. Z. Pang ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Meat Quality ◽  
Muscle Development ◽  
Expression Patterns ◽  
Subcutaneous Fat ◽  
Biceps Femoris ◽  
Longissimus Dorsi ◽  
Expression Levels ◽  
Longissimus Dorsi Muscle ◽  
Dorsi Muscle

Extracellular matrix (ECM) is the major macromolecule in skeletal muscle, and collagen is main component of ECM surrounding muscle fiber and adipocyte, which affect meat quality greatly. The remodeling of ECM is regulated by matrix metalloproteinases, such as ADAMTS2, which is essential for the maturation of triple helical collagen fibrils in body. The expression patterns of COL1A1, COL2A1, COL3A1 and ADAMTS2 in longissimus dorsi muscle were explored by qRT-PCR and results indicated that the expression levels of COL1A1, COL3A1 and ADAMTS2 were significantly higher at 3 and 24 month, while significantly lower at 12 and 30 month. The expression of ADAMTS2 and COL1A1 had significant positive relationships with intramuscular fat content, while expression of COL3A1 had significant positive relationship with shearing force and water holding capacity in cattle. The expression levels of collagen and ADAMTS2 were significantly higher in mesenteric fat, mammary fat pad and subcutaneous fat than in longissimus dorsi muscle, biceps femoris and infraspinitus tissues. The expressions levels of COL1A1, COL3A1 and ADAMTS2 were significantly lower in marbling fat than in other fat tissues. This study indicated that the expression of collagen and ADAMTS2 had important effects on postnatal skeletal muscle development and meat quality.

scholarly journals Muscle-Derived Extracellular Signal-Regulated Kinases 1 and 2 Are Required for the Maintenance of Adult Myofibers and Their Neuromuscular Junctions

2015 ◽  
Vol 35 (7) ◽  
pp. 1238-1253 ◽  
Author(s):  
Bonnie Seaberg ◽  
Gabrielle Henslee ◽  
Shuo Wang ◽  
Ximena Paez-Colasante ◽  
Gary E. Landreth ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Tibialis Anterior ◽  
Neuromuscular Junctions ◽  
Germ Line ◽  
Fiber Type ◽  
Postnatal Growth ◽  
Mammalian Skeletal Muscle ◽  
Neuromuscular Synapses ◽  
Extracellular Signal

The Ras–extracellular signal-regulated kinase 1 and 2 (ERK1/2) pathway appears to be important for the development, maintenance, aging, and pathology of mammalian skeletal muscle. Yet no gene targeting ofErk1/2in muscle fibersin vivohas been reported to date. We combined a germ lineErk1mutation with Cre-loxPErk2inactivation in skeletal muscle to produce, for the first time, mice lacking ERK1/2 selectively in skeletal myofibers. Animals lacking muscle ERK1/2 displayed stunted postnatal growth, muscle weakness, and a shorter life span. Their muscles examined in this study, sternomastoid and tibialis anterior, displayed fragmented neuromuscular synapses and a mixture of modest fiber atrophy and loss but failed to show major changes in fiber type composition or absence of cell surface dystrophin. Whereas the lack of only ERK1 had no effects on the phenotypes studied, the lack of myofiber ERK2 explained synaptic fragmentation in the sternomastoid but not the tibialis anterior and a decrease in the expression of the acetylcholine receptor (AChR) epsilon subunit gene mRNA in both muscles. A reduction in AChR protein was documented in line with the above mRNA results. Evidence of partial denervation was found in the sternomastoid but not the tibialis anterior. Thus, myofiber ERK1/2 are differentially required for the maintenance of myofibers and neuromuscular synapses in adult mice.

scholarly journals The transition from fetal growth restriction to accelerated postnatal growth: a potential role for insulin signalling in skeletal muscle

2009 ◽  
Vol 587 (17) ◽  
pp. 4199-4211 ◽  
Author(s):  
B. S. Muhlhausler ◽  
J. A. Duffield ◽  
S. E. Ozanne ◽  
C. Pilgrim ◽  
N. Turner ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Fetal Growth ◽  
Fetal Growth Restriction ◽  
Potential Role ◽  
Insulin Signalling ◽  
Postnatal Growth ◽  
Growth Restriction

scholarly journals Muskelwachstum und IGF-I bei Schweinen unterschiedlichen Geschlechts*

1999 ◽  
Vol 42 (6) ◽  
pp. 619-628
Author(s):  
S. Biereder ◽  
M. Wicke ◽  
G. von Lengerken ◽  
F. Schneider ◽  
W. Kanitz
Keyword(s):  
Skeletal Muscle ◽  
Blood Plasma ◽  
Muscle Fibre ◽  
Plasma Concentrations ◽  
Fibre Diameter ◽  
Postnatal Growth ◽  
Muscle Fibres ◽  
Triceps Brachii ◽  
Muscle Area ◽  
Igf I

Abstract. Title ofthe paper: Growth of skeletal muscle and IGF-I in pigs of different sex IGF-I is a pluripotent factor that is involved in regulation of growth, differentiation and a large number of functions in numerous tissues and their cells. IGF-I is synthesized by hepatocytes (endocrine role) and several extrahepatic tissues (e.g. skeletal muscle; autoerine and paracrine role). In our study, we describe the postnatal growth of the skeletal muscles in pigs of various sex taking into account the possible influence of endogenous IGF-I. The investigation was made on 42 crossbred pigs. Seven blood samples and 4 biopsy samples of two muscles (M. longissimus dorsi and M. triceps brachii) were taken for the determination of IGF-I blood plasma concentration and muscle fibre diameter, respectively as well as for further muscle structural and biochemical traits. IGF-I plasma concentrations show an increase during fattening with significantly highest levels for boars. Phenotypic differences between sows and boars in thickness of Shoulder muscle are proven after the day 181 with ultrasonography because significant differences were detected in mean muscle area of caput longum musculi triceps brachii between sows and boars and barrows (180th day of life). There are no significant differences in mean muscle fibre diameter of both muscles between sexes. A group of animals with high mean diameter in muscle fibres (day 200) of M. triceps brachii has significantly higher IGF-I concentrations in blood plasma than a group of animals with low muscle fibre diameter in the same muscle.

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