Stimulation Of Protein Synthesis Research Articles

Deletion of Asb15b gene can lead to a significant decrease in zebrafish intermuscular bone

Intermuscular bones, which are present in numerous economically significant fish species, have a negative impact on the development of aquaculture. The Asb15b gene, primarily expressed in skeletal muscle, plays a crucial role in regulating protein turnover and the development of muscle fibers. It stimulates protein synthesis and controls the differentiation of muscle fibers. In this study, we employed CRISPR/Cas9 technology to generate homozygous zebrafish strains with 7 bp and 49 bp deletions in the Asb15b gene. Subsequent analyses using skeleton staining demonstrated a substantial reduction in the number of intermuscular bones in adult Asb15b−/− −7 bp and Asb15b−/− −49 bp mutants compared to the wild-type zebrafish, with decreases of 30 % (P < 0.001) and 40 % (P < 0.0001), respectively. Histological experiments further revealed that the diameter and number of muscle fibers in adult Asb15b−/− mutants did not exhibit significant changes when compared to wild-type zebrafish. Moreover, qRT-PCR experiments demonstrated significant differences in the expression of bmp6 and runx2b genes, which are key regulators of intermuscular bone development, during different stages of intermuscular bone development in Asb15b−/− mutants. This study strongly suggests that the Asb15b gene plays a crucial role in regulating intermuscular bone development in fish and lays the groundwork for further exploration of the role of the Asb15b gene in zebrafish intermuscular bone development.

Cornflower Extract and Its Active Components Alleviate Dexamethasone-Induced Muscle Wasting by Targeting Cannabinoid Receptors and Modulating Gut Microbiota.

Sarcopenia, a decline in muscle mass and strength, can be triggered by aging or medications like glucocorticoids. This study investigated cornflower (Centaurea cyanus) water extract (CC) as a potential protective agent against DEX-induced muscle wasting in vitro and in vivo. CC and its isolated compounds mitigated oxidative stress, promoted myofiber growth, and boosted ATP production in C2C12 myotubes. Mechanistically, CC reduced protein degradation markers, increased mitochondrial content, and activated protein synthesis signaling. Docking analysis suggested cannabinoid receptors (CB) 1 and 2 as potential targets of CC compounds. Specifically, graveobioside A from CC inhibited CB1 and upregulated CB2, subsequently stimulating protein synthesis and suppressing degradation. In vivo, CC treatment attenuated DEX-induced muscle wasting, as evidenced by enhanced grip strength, exercise performance, and modulation of muscle gene expression related to differentiation, protein turnover, and exercise performance. Moreover, CC enriched gut microbial diversity, and the abundance of Clostridium sensu stricto 1 positively correlated with muscle mass. These findings suggest a multifaceted mode of action for CC: (1) direct modulation of the muscle cannabinoid receptor system favoring anabolic processes and (2) indirect modulation of muscle health through the gut microbiome. Overall, CC presents a promising therapeutic strategy for preventing and treating muscle atrophy.

The Effect of Chronic Dietary Protein Manipulation on Amino Acids' Profile and Position Sense in the Elderly Suffering from Type 2 Diabetes Mellitus.

Dietary protein with adequate essential amino acids effectively stimulates protein synthesis and improves muscle mass. Musculoskeletal disorders in lower or upper limbs are not uncommon among patients with type II diabetes mellitus (T2DM). Therefore, this study primarily examines the effects of chronic dietary protein manipulation on amino acids' profile and position sense in the elderly suffering from T2DM. A total of 26 individuals suffering from non-insulin-dependent T2DM (age > 55 years old) participated in a 12 week nutritional intervention. The subjects were randomly assigned and the control group received 0.8-1.0 g protein/kg/day, while the intervention group received 1.2-1.5 g protein/kg/day. Lean body mass, muscle strength, and position sense were assessed at baseline, as well as at the 6th and 12th week of the intervention. Only in the intervention group, the essential amino acids intake met the current nutritional recommendations (p < 0.05), while, by the 12th week, only the intervention group showed significant improvement in the muscle strength of knee (p < 0.05) and shoulder (p < 0.05) extension. On the contrary, in the control group, a significant decline in appendicular lean mass (p < 0.05) was observed by the 12th week. Position sense at the knee joint revealed a tendency for improvement in the intervention group by the 12th week (main effect of time p = 0.072). In the present investigation, it was revealed that the higher protein intake in the intervention group seemed to have positive effects on muscle strength and nearly positive effects on position sense.

Therapeutic benefit of oregano oil in the acute idiosyncratic hepatotoxicity induced by carbon tetrachloride in rats: Adverse effects of high dose of oreganum.

Toxicity caused by carbon tetrachloride (CCl4) can lead to serious liver injury. The aim of the study is to investigate the protective effects of oregano oil (Origanum minutiflorum extract oil) against CCl4-induced liver injury. Two doses of oregano oil were used in the experiment: a low dose (LD; 20 mg/kg) and a high dose (HD; 60 mg/kg) during 2 weeks. CCl4 caused severe liver damage, nucleolus destruction in hepatocytes and cytogenetic changes in the nucleus. Indirectly, CCl4 causes decreased protein synthesis and significantly high creatinine and urea values. Hematological disorders have been recorded, such as decreased RBC and hemoglobin concentration, increased WBC and deformability of the erythrocyte membrane. Both doses of oregano oil had protective effects. Improved protein synthesis and high globulins level, creatinine and urea were found in both groups. Cytogenetic changes in the nucleus of hepatocytes were reduced. A high dose of oregano oil had maximal protective effects for RBC, but a very weak effect on hemoglobin synthesis. Also, WBC and lymphocyte values were low. Origanum stimulates protein synthesis and recovery of hepatocytes after liver injury, reduces the deformability of the erythrocyte membrane. High doses of oregano oil decreased WBC and lymphocytes which may lead to a weakening of the immune response. However, high doses are more effective against severe platelet aggregation than low doses, suggesting an effective treatment against thrombocytosis.

Stimulation of muscle protein synthesis with low-dose amino acid composition in older individuals.

Essential amino acid (EAA)-based compositions have been shown to be effective stimulators of muscle protein synthesis, but the lower limit of effective dosage is not clear. We have used stable isotope tracer methodology to quantify the response of muscle protein fractional synthetic rate (FSR) to a dose of 3.6 g of a high-leucine composition of EAAs plus arginine in older subjects. Muscle protein FSR increased 0.058%/hour over 3 h following consumption. When account was taken of the total muscle mass, this increase in muscle protein FSR represented approximately 80% of ingested EAAs. We conclude that a low dose of an EAA-based composition can effectively stimulate muscle protein synthesis.

Modern realities of correction of skin barrier disorders in various diseases

Skin xerosis is a common symptom that indicates of impaired skin barrier function. Such diseases as atopic dermatitis (AD) and ichthyosis are associated with genetic mutations of epidermal differentiation genes, while in other diseases (contact dermatitis, eczema) epidermal barrier disorders occur as a result of inflammatory process in the skin, mechanical or chemical damage, significantly affecting the course of the pathological process. The article highlights modern data on the importance of the main structural protein of the stratum corneum filaggrin (FLG) and the role of its deficiency not only in dermatologic diseases, but also in the development of hyperresponsiveness. The main methods of correction of skin barrier disorders are emollients, which belong to the methods of basic therapy in AD and are recommended for the complex therapy of other pathological conditions accompanied by xerosis. At the present time, an innovative method has been developed, that allows not only to replace FLG deficiency, but also to activate and stimulate protein synthesis in the skin. In this regard, a unique dermatocosmetics product “Admera”, which belongs to the category of “emollients plus” due to the combination of all the necessary properties of the emollient and the presence of FLG synthesis modulator filagrinol, is of interest. Filagrinol is a proprietary complex of active ingredients that activate enzymes involved in dephosphorylation of the FLG predecessor profilaggrin and increase the concentration in the stratum granulosum сells of a histidine-rich glycoprotein, involved in the formation of the stratum corneum cytoskeleton. The article presents a review of clinical studies on the efficacy of Admera cream and presents our own clinical experience of its use in patients with AD and hand eczema.

Mitochondrial Quantity and Quality in Age-Related Sarcopenia.

Sarcopenia, the age-associated decline in skeletal muscle mass and strength, is a condition with a complex pathophysiology. Among the factors underlying the development of sarcopenia are the progressive demise of motor neurons, the transition from fast to slow myosin isoform (type II to type I fiber switch), and the decrease in satellite cell number and function. Mitochondrial dysfunction has been indicated as a key contributor to skeletal myocyte decline and loss of physical performance with aging. Several systems have been implicated in the regulation of muscle plasticity and trophism such as the fine-tuned and complex regulation between the stimulator of protein synthesis, mechanistic target of rapamycin (mTOR), and the inhibitor of mTOR, AMP-activated protein kinase (AMPK), that promotes muscle catabolism. Here, we provide an overview of the molecular mechanisms linking mitochondrial signaling and quality with muscle homeostasis and performance and discuss the main pathways elicited by their imbalance during age-related muscle wasting. We also discuss lifestyle interventions (i.e., physical exercise and nutrition) that may be exploited to preserve mitochondrial function in the aged muscle. Finally, we illustrate the emerging possibility of rescuing muscle tissue homeostasis through mitochondrial transplantation.

Acute ingestion of a ketone monoester, whey protein, or their co-ingestion in the overnight postabsorptive state elicit a similar stimulation of myofibrillar protein synthesis rates in young males: a double-blind randomized trial

BackgroundKetone bodies may have anabolic effects in skeletal muscle via their capacity to stimulate protein synthesis. Whether orally ingested exogenous ketones can stimulate postprandial myofibrillar protein synthesis (MyoPS) rates with and without dietary protein co-ingestion is unknown. ObjectivesThis study aimed to evaluate the effects of ketone monoester intake and elevated blood β-hydroxybutyrate (β-OHB) concentration, with and without dietary protein co-ingestion, on postprandial MyoPS rates and mechanistic target of rapamycin complex 1 (mTORC1) pathway signaling. MethodsIn a randomized, double-blind, parallel group design, 36 recreationally active healthy young males (age: 24.2 ± 4.1 y; body fat: 20.9% ± 5.8%; body mass index: 23.4 ± 2 kg/m2) received a primed continuous infusion of L-[ring-2H5]-phenylalanine and ingested one of the following: 1) the ketone monoester (R)-3-hydroxybutyl (R)-3-hydroxybutyrate (KET), 2) 10 g whey protein (PRO), or 3) the combination of both (KET+PRO). Blood and muscle biopsy samples were collected during basal and postprandial (300 min) conditions to assess β-OHB, glucose, insulin, and amino acid concentrations, MyoPS rates, and mTORC1 pathway signaling. ResultsCapillary blood β-OHB concentration increased similarly during postprandial conditions in KET and KET+PRO, with both being greater than PRO from 30 to 180 min (treatment × time interaction: P < 0.001). Postprandial plasma leucine and essential amino acid (EAA) incremental area under the curve (iAUC) over 300 min was greater (treatment: both P < 0.001) in KET+PRO compared with PRO and KET. KET, PRO, and KET+PRO stimulated postprandial MyoPS rates (0–300 min) higher than basal conditions [absolute change: 0.020%/h; (95% CI: 0.013, 0.027%/h), 0.014%/h (95% CI: 0.009, 0.019%/h), 0.019%/h (95% CI: 0.014, 0.024%/h), respectively (time: P < 0.001)], with no difference between treatments (treatment: P = 0.383) or treatment × time interaction (interaction: P = 0.245). mTORC1 pathway signaling responses did not differ between treatments (all P > 0.05). ConclusionsAcute oral intake of a ketone monoester, 10 g whey protein, or their co-ingestion in the overnight postabsorptive state elicit a similar stimulation of postprandial MyoPS rates in healthy young males.This trial was registered at clinicaltrials.gov as NCT04565444 (https://clinicaltrials.gov/study/NCT04565444).

Management of disease-related malnutrition: a real-world experience with a novel concentrated high-protein energy-dense oral nutritional supplement

ABSTRACT Objective Despite the availability of a wide range of oral nutritional supplements (ONS) offerings, individuals with malnutrition are still struggling to meet their nutritional targets. A new concentrated and high-protein energy-dense ONS (≥2.1 kcal/mL;32 g protein/200 mL) with high-quality protein (60% whey protein) has emerged as a pivotal formula to reach the patient’s energy-protein requirements, enhance compliance, and maximize stimulation of muscle protein synthesis, key factors driving better nutritional, functional, and clinical outcomes. The purpose of this article is to provide our clinical experience using this new nutritionally concentrated ONS as a therapeutic strategy for patients with DRM. Methods Three clinical cases have been examined using new assessment procedures and a new form of nutritional therapy, and their impact on the nutritional and functional outcomes in patients with moderate-to-severe DRM. Results A tailored individualized nutritional interventions improved anthropometric, biochemical, and functional outcomes (Case 1,2, and 3) assessed using hand grip strength, bioimpedance and muscle ultrasound, and as well as good gastrointestinal tolerance (Case 1) and compliance to the ONS in patients with DRM (Case 1,2,3). Conclusion The use of this novel high-protein energy-dense formula with high-quality protein source (≥2.1 kcal/mL; 32 g protein/200 mL; 60% whey protein) overcome common practical challenges in the medical nutrition therapy of patients with DRM, either because these patients require a highly concentrated formulation to meet nutritional requirements due to loss of appetite, lack of interest in food, and high caloric-protein needs due to disease, and a large quantity and quality of protein to optimize muscle recovery due to sarcopenia, common in patients with moderate-severe malnutrition.

ОСОБЕННОСТИ ГЕМАТОЛОГИЧЕСКОГО ПРОФИЛЯ ГЛУБОКОСТЕЛЬНЫХ И НОВОТЕЛЬНЫХ КОРОВ НА ФОНЕ ПРИМЕНЕНИЯ БИОСТИМУЛЯТОРОВ (сообщение 2)

This article data on differentiated counting of the number of leukocytes are given, as well as the dynamics of total protein and protein fractions in the blood of animals, indicating the level of metabolic processes in a living organism, is determined. It has been established that intramuscular application of experimental biological preparations to cows 65-60, 45-40 and 25-20 days before calving stimulates the process of hematopoiesis, activates cellular factors of non-specific resistance (physiological leukocytosis, moderate eosinophilia and neutropenia with a right shift of the nucleus, lymphocytosis). The most pronounced effect was noted with three injections of the complex biological product Prevention-N-A-M. Biological preparations Prevention-N-A-M and PS-7 stimulate protein synthesis (albumins, α-, β-, γ-globulins) in the body before and after calving. The obtained results testify to the effectiveness of the tested biopreparations and make it possible to scientifically substantiate the feasibility of their use in animal husbandry as an effective way to increase the resistance of the body of cows, which can significantly improve their health and reduce the risk of diseases.

Stepwise Discovery of Insulin Effects on Amino Acid and Protein Metabolism.

A clear effect of insulin deficiency and replacement on body/muscle mass was a landmark observation at the start of the insulin age. Since then, an enormous body of investigations has been produced on the pathophysiology of diabetes mellitus from a hormonal/metabolic point of view. Among them, the study of the effects of insulin on body growth and protein accretion occupies a central place and shows a stepwise, continuous, logical, and creative development. Using a metaphor, insulin may be viewed as a director orchestrating the music (i.e., the metabolic effects) played by the amino acids and proteins. As a hormone, insulin obviously does not provide either energy or substrates by itself. Rather, it tells cells how to produce and utilize them. Although the amino acids can be released and taken up by cells independently of insulin, the latter can powerfully modulate these movements. Insulin regulates (inhibits) protein degradation and, in some instances, stimulates protein synthesis. This review aims to provide a synthetic and historical view of the key steps taken from the discovery of insulin as an "anabolic hormone", to the in-depth analysis of its effects on amino acid metabolism and protein accretions, as well as of its interaction with nutrients.

Bckdk-Mediated Branch Chain Amino Acid Metabolism Reprogramming Contributes to Muscle Atrophy during Cancer Cachexia.

Branched chain amino acids (BCAAs) are essential amino acids and important nutrient signals for energy and protein supplementation. The study uses muscle-specific branched-chain α-keto acid dehydrogenase kinase (Bckdk) conditional knockout (cKO) mice to reveal the contribution of BCAA metabolic dysfunction to muscle wasting. Muscle-specific Bckdk-cKO mice are generated through crossbreeding of Bckdkf/f mice with Myf5Cre mice. Lewis lung cancer (LLC) tumor transplantation is used to establish the cancer cachexia model. The occurrence of cancer cachexia is accelerated in the muscle-specific Bckdk-cKO mice after bearing LLC tumor. Wasting skeletal muscle is characterized by increased protein ubiquitination degradation and impaired protein synthesis. The wasting muscle gastrocnemius is mechanized as a distinct BCAA metabolic dysfunction. Based on the atrophy phenotype resulting from BCAA metabolism dysfunction, the optimized BCAA supplementation improves the survival of cancer cachexia in muscle-specific Bckdk-cKO mice bearing LLC tumors, and improves the occurrence of cancer cachexia. The mechanism of BCAA supplementation on muscle mass preservation is based on the promotion of protein synthesis and the inhibition of protein ubiquitination degradation. Dysfunctional BCAA metabolism contributes to the inhibition of protein synthesis and increases protein degradation in the cancer cachexia model of muscle-specific Bckdk-cKO mice bearing LLC tumors. The reprogramming of BCAA catabolism exerts therapeutic effects by stimulating protein synthesis and inhibiting protein degradation in skeletal muscle.

Tyrosine Is a Booster of Leucine-Induced Muscle Anabolic Response.

Leucine (Leu), an essential amino acid, is known to stimulate protein synthesis in the skeletal muscle via mTOR complex 1 (mTORC1) activation. However, the intrinsic contribution of other amino acids to Leu-mediated activation of mTORC1 signaling remains unexplored. This study aimed to identify amino acids that can promote mTORC1 activity in combination with Leu and to assess the effectiveness of these combinations in vitro and in vivo. We found that tyrosine (Tyr) enhanced Leu-induced phosphorylation of S6 kinase (S6K), an indicator of mTORC1 activity, although it exerted no such effect individually. This booster effect was observed in C2C12 cells, isolated murine muscle, and the skeletal muscles of mice orally administered the amino acids. To explore the molecular mechanisms underlying this Tyr-mediated booster effect, the expression of the intracellular Leu sensors, Sestrin1 and 2, was suppressed, and the cells were treated with Leu and Tyr. This suppression enabled Tyr alone to induce S6K phosphorylation and enhanced the booster effect, suggesting that Tyr possibly contributes to mTORC1 activation when Sestrin-GAP activity toward Rags 2 (GATOR2) is dissociated through Sestrin knockdown or the binding of Sestrins to Leu. Collectively, these results indicate that Tyr is a key regulator of Leu-mediated protein synthesis.

Ca and Mg stimulate protein synthesis in maize kernel through the action of endogenous hormones and defense enzymes

Soil calcium (Ca) and magnesium (Mg) mineral states in rain-fed arid regions of Northwest China are inefficient, and their levels of substitution and water-soluble states are far below the lowest threshold required for maize growth, resulting in frequent physiological diseases, restricting synthesis of kernel protein (CRP). Our study set up different levels of foliar spraying of Ca and Mg fertilizers before maize pollination to examine the response characteristics of physiological and biochemical indicators in kernel, and the driving process of CRP synthesis. The main findings were: (1) Ca and Mg significantly increased the levels of CRP and endogenous hormones, and the activities of defense enzymes and CRP synthesis enzymes, which decreased significantly and stabilized at the maturity stage of maize. (2) The synthesis and accumulation of CRP were synergistically regulated by endogenous hormones, defense enzymes, and CRP synthase enzymes, with the degree of regulation varying with the level of Ca and Mg supplementation. Indole-3-acetic acid (IAA), gibberellin (GA), zeatin riboside (ZR), catalase (CAT), malondialdehyde (MDA), and glutamate dehydrogenase (GDH) were the primary physiological driving indicators of CRP synthesis, with CRP having a significant synergistic relationship with CAT and a remarkable trade-off with other driving indicators. (3) The dominant driving pathway of CRP synthesis was “Ca, Mg-IAA or GA or ZR-CAT-GDH-CRP”. Ca and Mg positively affected IAA and GA levels, and IAA and GA positively regulated CAT activity. However, CAT negatively regulated GDH levels, causing GDH to negatively influence the synthesis and accumulation of CRP and its components. The findings provide theoretical support for further study of inter-root endogenous hormones and soil microbe-driven processes in the regulation of maize quality by Ca and Mg.

Long-chain n-3 PUFA ingestion for the stimulation of muscle protein synthesis in healthy older adults.

This review aims to critically evaluate the efficacy of long-chain ո-3 PUFA ingestion in modulating muscle protein synthesis (MPS), with application to maintaining skeletal muscle mass, strength and function into later life. Ageing is associated with a gradual decline in muscle mass, specifically atrophy of type II fibres, that is exacerbated by periods of (in)voluntary muscle disuse. At the metabolic level, in otherwise healthy older adults, muscle atrophy is underpinned by anabolic resistance which describes the impaired MPS response to non-pharmacological anabolic stimuli, namely, physical activity/exercise and amino acid provision. Accumulating evidence implicates a mechanistic role for n-3 PUFA in upregulating MPS under stimulated conditions (post-prandial state or following exercise) via incorporation of EPA and DHA into the skeletal muscle phospholipid membrane. In some instances, these changes in MPS with chronic ո-3 PUFA ingestion have translated into clinically relevant improvements in muscle mass, strength and function; an observation evidently more prevalent in healthy older women than men. This apparent sexual dimorphism in the adaptive response of skeletal muscle metabolism to EPA and DHA ingestion may be related to a greater propensity for females to incorporate ո-3 PUFA into human tissue and/or the larger dose of ingested ո-3 PUFA when expressed relative to body mass or lean body mass. Future experimental studies are warranted to characterise the optimal dosing and duration of ո-3 PUFA ingestion to prescribe tailored recommendations regarding n-3 PUFA nutrition for healthy musculoskeletal ageing into later life.

Research progress in the role and mechanism of Leucine in regulating animal growth and development.

Leucine, a branched-chain amino acid, is essential in regulating animal growth and development. Recent research has uncovered the mechanisms underlying Leucine's anabolic effects on muscle and other tissues, including its ability to stimulate protein synthesis by activating the mTORC1 signaling pathway. The co-ingestion of carbohydrates and essential amino acids enhances Leucine's anabolic effects. Moreover, Leucine has been shown to benefit lipid metabolism, and insulin sensitivity, making it a promising strategy for preventing and treating metabolic diseases, including type 2 diabetes and obesity. While emerging evidence indicates that epigenetic mechanisms may mediate Leucine's effects on growth and development, more research is needed to elucidate its mechanisms of action fully. Specific studies have demonstrated that Leucine promotes muscle growth and metabolic health in animals and humans, making it a promising therapeutic agent. However, it is essential to note that Leucine supplementation may cause digestive issues or interact with certain medications, and More study is required to determine definitively optimal dosages. Therefore, it is important to understand how Leucine interacts with other nutrients, dietary factors, and lifestyle habits to maximize its benefits. Overall, Leucine's importance in human nutrition is far-reaching, and its potential to prevent muscle loss and enhance athletic performance warrants further investigation.

261 Variations in Protein Deposition Might Be Associated with Insulin Resistance and Differences in Amino Acids Metabolism in Growing Gilts

Abstract Pigs with similar body weight (BW), same genetic background and sex vary in terms of protein deposition (PD) overgrowth. Insulin stimulates protein synthesis, and differences in PD could be associated with the variation among pigs in postprandial insulin secretion. Therefore, this study aimed to investigate if changes in preprandial and postprandial amino acids (AA) response and insulin resistance differ between pigs having Low or High PD. Seventy gilts (33 kg BW, ± 3.6; Alphagène) were assigned to a randomized complete block (BW) design and housed in the same pen equipped with automatic feeders. Pigs were fed ad libitum with a diet balanced to maximize PD. Dual X-Ray estimated body protein (BP) and lipid (BL) masses on d 1 and 21, and by difference, PD was calculated. On d 23, pigs were grouped in Low (157 g/d) and High (219 g/d) PD. Eight pigs per PD group were canulated in a jugular vein, and after 48h recovery receiving feed at 90% of the measured feed intake, they were fasted for eight hours to study preprandial metabolism (-5, -1 min before the meal). In sequence, all pigs received a 300 g meal and blood samples were collected at 10, 15, 20, 30, 40, 50, 60, 75, 90, 120, 150, 178, 178 min, relative to the meal, to measure AA, insulin and glucose concentrations. In addition, insulin resistance (HOMA-IR) was calculated based on fasting glucose and insulin concentrations. The AA response was modeled for each PD group based on the average group response using differential equations derived from the Erlang equation. Thus, the basal concentration, area under the curve (AUC) and AA flux could be compared among groups using the parameters obtained by the non-linear model. An F-test was used to compare the difference in the indexes between Low and High PD pigs. The basal concentration of methionine, valine and leucine were similar, whereas AUC was greater for Low PD pigs with no difference in flux, with the exception of methionine (P &amp;lt; 0.10; Table 1). Conversely, lysine (15%) and threonine (10%) basal concentrations were less in Low PD pigs. Lysine AUC was greater (8%), whereas others AA AUC were on average 27% less for High PD than for Low PD pigs. Lysine maximal concentration was 11% greater for High PD pigs and occurred later than for Low PD (1.15h vs 1.03h). Such differences in AA postprandial metabolism might be partially due to metabolic differences in response to anabolic hormones such as insulin. For instance, HOMA-IR differed (P &amp;lt; 0.05) among PD categories, with Low PD showing a 44% lower index for insulin resistance than high PD pigs. High PD pigs are less insulin-resistant and show differences in pre- and postprandial AA metabolism.

238 Leucine Supplementation Enhances Protein Synthesis in Lean Tissue Through a Sestrin2-GATOR2 and Raga-mTORC1 Signaling Pathway in a Preterm Piglet Model

Abstract Extrauterine growth restriction is common in preterm infants and is associated with reduced lean growth and long-term morbidities. We previously showed that leucine (Leu) acts as a nutrient signal to stimulate protein synthesis, and that in neonatal pigs born at term intermittent parenteral Leu pulses during continuous feeding increases skeletal muscle mTORC1 signaling and protein synthesis. The objective of this study was to determine the validity of the hypothesis that leu pulsing during continuous feeding enhances mTORC1 signaling via a Sestrin-mediated pathway to increase protein synthesis in lean tissue in the preterm piglet. Pigs delivered by cesarean section at 105 d gestation were continuously fed a protein and energy balanced milk-replacer diet [195 kcal ME and 13.5 g protein (kg body weight; BW)-1·d-1)]. Pigs (n = 11-12) were randomly assigned to Leu (LEU) or Alanine (ALA, isonitrogenous control) groups and treatments were administered as a pulse (1.6 mmol·kg BW-1·h-1) for 1 h every 4 h for 21 d. Indices of amino acid signaling and mTORC1 activation were determined postprandially, 60 min after initiation of the last pulse on day 24. Final body weight was greater (P &amp;lt; 0.05) and longissimus muscle weight was heavier in LEU than ALA pigs (P = 0.01). Upstream of mTORC1 activation, the abundance of the Sestrin2-GATOR2 complex was less and the RagA-mTORC1 complex was greater in longissimus muscle and gastrocnemius muscle of LEU compared with ALA pigs (P &amp;lt; 0.05). Downstream of mTORC1, the phosphorylation of S6K1 and 4EBP1 and abundance of the eIF4E-eIF4G complex were greater in longissimus muscle and gastrocnemius muscle of LEU compared with ALA pigs (P &amp;lt; 0.05). Fractional rates of protein synthesis in longissimus muscle and gastrocnemius muscle were greater in LEU compared with ALA pigs (P &amp;lt; 0.05). These results show that leucine supplementation enhances mTORC1-activated translation initiation in skeletal muscle of the preterm piglet via a Leu-sensing pathway mediated bySestrin2 and the Rag proteins. This leucine-mediated cascade promotes skeletal muscle and body weight gain by increasing muscle protein synthesis.

Does the blunted stimulation of skeletal muscle protein synthesis by aging in response to mechanical load result from impaired ribosome biogenesis?

Age-related loss of skeletal muscle mass leads to a reduction of strength. It is likely due to an inadequate stimulation of muscle protein synthesis (MPS) in response to anabolic stimuli, such as mechanical load. Ribosome biogenesis is a major determinant of translational capacity and is essential for the control of muscle mass. This mini-review aims to put forth the hypothesis that ribosome biogenesis is impaired by aging in response to mechanical load, which could contribute to the age-related anabolic resistance and progressive muscle atrophy. Recent animal studies indicate that aging impedes muscle hypertrophic response to mechanical overload. This is associated with an impaired transcription of ribosomal DNA (rDNA) by RNA polymerase I (Pol I), a limited increase in total RNA concentration, a blunted activation of AKT/mTOR pathway, and an increased phosphorylation of AMPK. In contrast, an age-mediated impairment of ribosome biogenesis is unlikely in response to electrical stimulations. In human, the hypertrophic response to resistance exercise training is diminished with age. This is accompanied by a deficit in long-term MPS and an absence of increased total RNA concentration. The results addressing the acute response to resistance exercise suggest an impaired Pol I-mediated rDNA transcription and attenuated activation/expression of several upstream regulators of ribosome biogenesis in muscles from aged individuals. Altogether, emerging evidence indicates that impaired ribosome biogenesis could partly explain age-related anabolic resistance to mechanical load, which may ultimately contribute to progressive muscle atrophy. Future research should develop more advanced molecular tools to provide in-depth analysis of muscle ribosome biogenesis.

AGE AND OBESITY INTERFERES IN MUSCLE HYPERTROPHY IN RATS UNDERGOING HIIT TRAINING

Sarcopenic obesity is a condition characterized by the simultaneous presence of obesity andsarcopenia, which is the loss of muscle mass and function. Is a growing concern, especiallyamong the elderly population, and it is important to address both obesity and sarcopeniathrough lifestyle modifications, such as exercise and proper nutrition, to improve overallhealth and quality of life. Our study aimed to evaluate the effect of HIIT training on themuscle fiber area of the EDL muscle in obese rats of different ages. For that, Wistar rats, 7and 12 months old, submitted or not to a HFD diet were subjected to HIIT training, 3 times aweek, on alternate days, for 8 consecutive weeks. After the euthanasia EDL muscles wascollected and processed histologically. Our data showed that HIIT training was able topromote muscle hypertrophy even with consumption of this diet, indicating that practicingthis exercise can stimulate protein synthesis even under conditions of obesity.