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ABSTRACT The potential liability to hypercatabolism in lipodystrophy remains to be fully elucidated. Here we report a 28‐year‐old Japanese woman with acquired generalized lipodystrophy, who presented with recurrence of panniculitis and anemia. After corticosteroid treatment was started, she showed rapid reductions in body weight and lean mass by 15% at maximum, accompanied by an elevated urea nitrogen/creatinine ratio, which recovered almost fully as the corticosteroid treatment was tapered and discontinued. She had multiple risk factors for hypercatabolism: lack of metabolic reserves, insulin resistance, and hyperglycemia due to lipodystrophy, lowered daily activity due to anemia, persistent inflammation, and wasting associated with panniculitis, and relatively insufficient energy and protein intake during hospitalization. More attention should be paid to the potential liability to hypercatabolism in patients with lipodystrophy, and to skeletal muscle loss as an adverse effect of corticosteroid treatment in patients at high risk, such as those with diabetes or decreased metabolic reserves.

3-(4-Hydroxy-3-methoxyphenyl)propionic acid (HMPA), also known as dihydroferulic acid, is a hydroxycinnamic acid derivative that can be derived from the microbial transformation of dietary polyphenols or naturally obtained from fermented foods. Although numerous studies have documented its antioxidant and anti-obesity effects, the effect of HMPA on muscle function remains unknown. This study investigated the effects of HMPA on muscle strength and exercise endurance capacity. Mice were orally administered low and high doses of HMPA for 14 days and subjected to grip force and treadmill exhaustion tests to evaluate muscle function. Our results showed that HMPA-administered groups significantly enhanced absolute grip strength (p = 0.0256) and relative grip strength (p = 0.0209), and low-dose HMPA decreased the plasma level of blood urea nitrogen after exercise (p = 0.0183), but HMPA did not affect endurance performance. Low-dose HMPA administration increased Myf5 expression in sedentary mice (p = 0.0106), suggesting that low-dose HMPA may promote muscle development. Additionally, HMPA improved hepatic glucose and lipid metabolism, and inhibited muscular lipid metabolism and protein catabolism, as indicated by changes in mRNA expression levels of related genes. These findings suggest that HMPA may be a promising dietary supplement for muscle health and performance. [ABSTRACT FROM AUTHOR]

The potential liability to hypercatabolism in lipodystrophy remains to be fully elucidated. Here we report a 28‐year‐old Japanese woman with acquired generalized lipodystrophy, who presented with recurrence of panniculitis and anemia. After corticosteroid treatment was started, she showed rapid reductions in body weight and lean mass by 15% at maximum, accompanied by an elevated urea nitrogen/creatinine ratio, which recovered almost fully as the corticosteroid treatment was tapered and discontinued. She had multiple risk factors for hypercatabolism: lack of metabolic reserves, insulin resistance, and hyperglycemia due to lipodystrophy, lowered daily activity due to anemia, persistent inflammation, and wasting associated with panniculitis, and relatively insufficient energy and protein intake during hospitalization. More attention should be paid to the potential liability to hypercatabolism in patients with lipodystrophy, and to skeletal muscle loss as an adverse effect of corticosteroid treatment in patients at high risk, such as those with diabetes or decreased metabolic reserves. [ABSTRACT FROM AUTHOR]

Our understanding of metabolic alterations triggered by heat stress is incomplete, which limits the designing of nutritional strategies to mitigate negative productive and health effects. Thus, this study aimed to explore the metabolic responses of heat-stressed dairy cows to dietary supplementation with vitamin D3/Ca and vitamin E/Se. Twelve multiparous Holstein cows were enrolled in a split-plot Latin square design with two distinct vitamin E/Se supplementation levels, either at a low (ESe−, n = 6, 11.1 IU/kg vitamin E and 0.55 mg/kg Se) or a high dose (ESe+, n = 6 223 IU/kg vitamin E and 1.8 mg/kg Se) as the main plot. Treatment subplots, arranged in a replicated 3 × 3 Latin square design, comprised heat challenge (Temperature Humidity Index, THI: 72.0–82.0) supplemented with different levels of vitamin D3/Ca: either low (HS/DCa−, 1 012 IU/kg and 0.73%, respectively) or high (HS/DCa+, 3 764 IU/kg and 0.97%, respectively), and a pair-fed control group in thermoneutrality (THI = 61.0–64.0) receiving the low dose of vitamin D3/Ca (TN). The liquid chromatography-mass spectrometry-based metabolome profile was determined in blood plasma and milk sampled at the beginning (day 0) and end (day 14) of each experimental period. The results were analyzed for the effect of (1) TN vs. HS/ESe−/DCa−, and (2) the vitamin E/Se and vitamin D3/Ca supplementation. No group or group × day effects were detected in the plasma metabolome (false discovery rate, FDR > 0.05), except for triglyceride 52:2 being higher (FDR = 0.03) on day 0 than 14. Taurine, creatinine and butyryl-carnitine showed group × day interactions in the milk metabolome (FDR ≤ 0.05) as creatinine (+22%) and butyryl-carnitine (+190%) were increased (P 0.05) in plasma and milk, except for milk alanine which was lower (−69%, FDR = 0.03) in the E/Se+ groups, compared with E/Se−. Our results indicated that HS triggered more prominent changes in the milk than in the plasma metabolome, with consistent results in milk suggesting increased muscle catabolism, as reflected by increased creatinine, alanine and citrulline levels. Supplementing with high levels of vitamin E/Se or vitamin D3/Ca or their combination did not appear to affect the metabolic remodeling triggered by HS.

Proteins serve a range of physiological functions in health and in disease. Their overall structure is determined predominantly by the sequence of amino acids when they are synthesized, which in turn is a derivative of the sequence of nucleotides in the corresponding segment of DNA. There is a constant turnover of body protein, the rate of which exceeds dietary protein intake and therefore suggests a degree of recycling. Some amino acids that enter the body protein pool can be synthesized ('non-essential' amino acids) while others can only be obtained through dietary means ('essential' amino acids). During critical illness and significant trauma there appears to be dysregulation such that synthesis of some non-essential amino acids is limited, while there is an increase in amino acid oxidation. Modification of dietary intake to address the potential imbalance in illness is probably insufficient in isolation to prevent muscle wasting. [ABSTRACT FROM AUTHOR]

Objective: To investigate the beneficial outcomes of intraoperative enteral feeding in free‐flap regeneration after extended head and neck cancer resection and flap reconstruction surgery. Study Design: A pilot randomized, double‐blind, placebo‐controlled clinical trial. Setting: Single tertiary care center. Methods: Patients with advanced head and neck cancers requiring radical tumor resections and free‐flap reconstruction were randomly assigned to receive intraoperative enteral nutrition feeding (100 kcal/100 mL at 10‐20 mL/h) via a nasogastric tube during free‐flap reconstruction (n = 28) or continue fasting (n = 28). The primary outcome was impaired free‐flap regeneration that required surgical reintervention within 90 days after the operation. Participants were enrolled between April 2020 and January 2022; the 90‐day follow‐up ended in April 2022. Results: The incidence of total or partial flap failure was similar between the 2 groups (14.2% or n = 4 in each group), but the rate of wound dehiscence or edge necrosis was significantly reduced in the feeding group (n = 6 vs 0 for fasting vs feeding; absolute risk reduction, 25.0% [95% confidence interval, 6.9‐43.0]%; p = 0.022). Hospital stay length was shorter (p = 0.042) and hand grip strength was better preserved (p = 0.025) in the feeding group. Plasma concentrations of interleukin (IL)‐6 and IL‐8 after the operation increased significantly more in the fasting group. Perioperative adverse events did not differ between the 2 groups. Conclusion: Perioperative enteral feeding is a simple, safe, and effective approach to improve perioperative systemic catabolism and proinflammatory reactions, thereby enhancing early wound regeneration after major operations. [ABSTRACT FROM AUTHOR]

Introduction: Improving adaptive responses to exercise through dietary interventions, especially sports supplements, has been considered. The aim of the present study was to compare the effect of Leucine and L-arginine supplementation before and after resistance training on athletes' protein catabolism indices during Ramadan. Methods: In this study, 40 male bodybuilders were selected and randomly divided into four groups of resistance training (n=10) and resistance training group and Leucine supplementation (n=10), resistance training group and L-arginine supplementation (n=10) and the control group (n=10). Leucine and L-arginine tablets were poured as powder into 1g empty capsules and placebo was in the form of 1g capsules, the same shape, size and color of 1g Leucine and L-arginine tablets. The amount of supplements was 0.1g per kg of body weight. The training protocol of the two training groups was performed for eight weeks in three sessions per week.To analyze the data, the statistical method of analysis of covariance was used and to determine the differences between the groups, Bonferroni post hoc test and at a significant level in all tests, P≤0.05 was considered. Results: Statistical analysis did not show a significant difference between groups in uric acid variable (p=0.097). Also, the results showed that resistance training significantly decreased urea (p=0.001), creatinine (p=0.001) and increased hypoxanthine (p=0.000) and xanthine oxidase (p=0.000). Resistance training with Leucine and L-arginine supplementation increased there was a significant urea, creatinine and a significant decrease in hypoxanthine and xanthine oxidase compared to the resistance training group. There was a significant difference between the two groups of supplements only in the amount of xanthine oxidase. In the resistance training group and Leucine supplementation, the amount of xanthine oxidase was significantly greater than in the resistance training group and L-arginine supplementation. Conclusion: Finally,resistance training with Leucine and L-arginine supplementation in fasting athletes could provide a platform for reducing protein catabolism due to exercise and it can be said that coaches and athletes to reduce catabolism due to exercise. During Ramadan, they can take Leucine and L-arginine supplements to increase performance and reduce damage.

Background: Cystic Fibrosis (CF) patients historically suffered from undernutrition, infection and inflammation. Insulin insufficiency-related protein catabolism further compromised health. We aimed to determine whether insulin improves protein catabolism in CF youth with abnormal glucose tolerance (AGT)., Methods: This double-masked, placebo-controlled trial in CF youth age 10-25 with AGT who were in their usual state of health used triple-tracer stable-isotope methodology to measure protein turnover during a baseline test meal and after four weeks of insulin/placebo treatment. Healthy controls were assessed once. CF patients were randomized 1:1:1 to once-daily long-acting insulin (0.25 U/kg/d), three-times daily rapid-acting insulin (0.5 U/15gr carbohydrate), or injectable placebo., Results: Thirty CF patients completed the study. There were no differences in any measure of protein turnover between insulin- and placebo-treated subjects, including endogenous protein breakdown (primary study endpoint). In contrast to earlier studies, protein turnover in the 37 CF patients who completed the baseline meal was normal compared to 20 healthy controls. Meal isotope appeared in plasma earlier in CF than controls, suggesting more rapid gut emptying. The study was interrupted by the pandemic; futility analysis led to study discontinuation before the planned remaining 15 CF patients were studied., Conclusions: Recent advances in CF have led to remarkable clinical improvements. In this study, CF youth with AGT had normal protein catabolism at baseline. Pre-meal or daily basal insulin therapy, while safe and well tolerated, did not significantly enhance protein turnover and does not appear to be necessary in clinically stable patients prior to development of CFRD., Competing Interests: Declaration of competing interest Schiavon M: None, Cobelli C: None, Nair KS: None, Klaus K: None, Toffolo, G: None, Zhang L: None, Moran A: Over the last 5 years Dr. Moran reports serving on scientific advisory boards for Dompé Farmaceutici SpA, ProventionBio, Vertex Pharaceuticals and Abata Therapeutics; serving on data and safety monitoring boards funded by NovoNordisk and the Leona M. and Harry B. Helmsley Charitable Trust; her institution has received grant funding on her behalf from the NIH, JDRF, the Cystic Fibrosis Foundation, Abbott Diabetes, ProventionBio, Intrexon (now Precigen), and Caladrius Biosciences; she has received study supplies from Medtronic and Abbott Diabetes., (Copyright © 2024. Published by Elsevier B.V.)

Abstract Background Muscle atrophy is a common pathology associated with disuse, such as prolonged bed rest or spaceflight, and is associated with detrimental health outcomes. There is emerging evidence that disuse atrophy may differentially affect males and females. Cellular mechanisms contributing to the development and progression of disuse remain elusive, particularly protein turnover cascades. The purpose of this study was to investigate the initial development and progression of disuse muscle atrophy in male and female mice using the well‐established model of hindlimb unloading (HU). Methods One hundred C57BL/6J mice (50 male and 50 female) were hindlimb suspended for 0 (control), 24, 48, 72, or 168 h to induce disuse atrophy (10 animals per group). At designated time points, animals were euthanized, and tissues (extensor digitorum longus, gastrocnemius, and soleus for mRNA analysis, gastrocnemius and extensor digitorum longus for protein synthesis rates, and tibialis anterior for histology) were collected for analysis of protein turnover mechanisms (protein anabolism and catabolism). Results Both males and females lost ~30% of tibialis anterior cross‐sectional area after 168 h of disuse. Males had no statistical difference in MHCIIB fibre area, whereas unloaded females had ~33% lower MHCIIB cross‐sectional area by 168 h of unloading. Both males and females had lower fractional protein synthesis rates (FSRs) within 24–48 h of HU, and females appeared to have a greater reduction compared with males within 24 h of HU (~23% lower FSRs in males vs. 40% lower FSRs in females). Males and females exhibited differential patterns and responses in multiple markers of protein anabolism, catabolism, and myogenic capacity during the development and progression of disuse atrophy. Specifically, females had greater mRNA inductions of catabolic factors Ubc and Gadd45a (~4‐fold greater content in females compared with ~2‐fold greater content in males) and greater inductions of anabolic inhibitors Redd1 and Deptor with disuse across multiple muscle tissues exhibiting different fibre phenotypes. Conclusions These results suggest that the aetiology of disuse muscle atrophy is more complicated and nuanced than previously thought, with different responses based on muscle phenotypes and between males and females, with females having greater inductions of atrophic markers early in the development of disuse atrophy.

Hibernation requires balancing energy and water demands over several months. Many studies have noted the importance of fat for hibernation energy budgets, but protein catabolism in hibernation has received less attention, and whole-animal changes in lean mass have not previously been considered. We used quantitative magnetic resonance body composition analysis to measure deposition of fat and lean mass of cave myotis (Myotis velifer) during the prehibernation period and decreases in fat and lean mass of Townsend’s big-eared bats (Corynorhinus townsendii) during hibernation. For cave myotis, lean mass represented 25% and 38% (female and male, respectively) of prehibernation mass gain. In hibernating Townsend’s big-eared bats, lean mass decrease was similar for females and males. We used values for Townsend’s big-eared bats to explore the functional implications of lean mass change for water and energy budgets. Lean mass accounted for a substantial proportion of mass change during hibernation (female: 18%, male: 35%), and although not accounting for a large proportion of the energy budget (female: 3%, male: 7%), lean mass catabolism represented an important contribution to water production (female: 14%, male: 29%). Although most mammals cannot rely on protein catabolism for metabolic water production because of the water cost of excreting urea, we propose a variation of the protein-for-water strategy whereby hibernators could temporally compartmentalize the benefits of protein catabolism to periods of torpor and the water cost to periodic arousals when free drinking water is typically available. Combined, our analyses demonstrate the importance of considering changes in lean mass during hibernation. [ABSTRACT FROM AUTHOR]

Broiler chickens reared under heat stress (HS) conditions have decreased growth performance and show metabolic and immunologic alterations. This study aimed to evaluate the effect of supplementation with a standardized blend of plant-derived isoquinoline alkaloids (IQ) on the growth performance, protein catabolism, intestinal barrier function, and inflammatory status of HS-treated chickens. Three hundred sixty 0-day-old Ross 308 male broiler chickens were randomly distributed into 2 treatment groups: control diet (no additives) or diet supplemented with 100 ppm IQ. At day 14, the chicks in each diet group were further divided into 2 groups, each of which was reared under thermoneutral (TN) (22.4°C) or constant HS (33.0°C) conditions until day 42. Each group consisted of 6 replicates with 15 birds per replicate, and chickens were provided ad libitum access to water and feed. During days 15–21, the body weight gain (BWG) and feed intake (FI) were significantly lower in the HS treatment group than in the TN group, and feed conversion ratio was higher (P

Introduction: Improving adaptive responses to exercise through dietary interventions, especially sports supplements, has been considered. The aim of the present study was to compare the effect of Leucine and L-arginine supplementation before and after resistance training on athletes' protein catabolism indices during Ramadan. Methods: In this study, 40 male bodybuilders were selected and randomly divided into four groups of resistance training (n=10) and resistance training group and Leucine supplementation (n=10), resistance training group and L-arginine supplementation (n=10) and the control group (n=10). Leucine and L-arginine tablets were poured as powder into 1g empty capsules and placebo was in the form of 1g capsules, the same shape, size and color of 1g Leucine and L-arginine tablets. The amount of supplements was 0.1g per kg of body weight. The training protocol of the two training groups was performed for eight weeks in three sessions per week. To analyze the data, the statistical method of analysis of covariance was used and to determine the differences between the groups, Bonferroni post hoc test and at a significant level in all tests, P=0.05 was considered. Results: Statistical analysis did not show a significant difference between groups in uric acid variable (p=0.097). Also, the results showed that resistance training significantly decreased urea (p=0.001), creatinine (p=0.001) and increased hypoxanthine (p=0.000) and xanthine oxidase (p=0.000). Resistance training with Leucine and L-arginine supplementation increased there was a significant urea, creatinine and a significant decrease in hypoxanthine and xanthine oxidase compared to the resistance training group. There was a significant difference between the two groups of supplements only in the amount of xanthine oxidase. In the resistance training group and Leucine supplementation, the amount of xanthine oxidase was significantly greater than in the resistance training group and Larginine supplementation. Conclusion: Finally, resistance training with Leucine and L-arginine supplementation in fasting athletes could provide a platform for reducing protein catabolism due to exercise and it can be said that coaches and athletes to reduce catabolism due to exercise. During Ramadan, they can take Leucine and L-arginine supplements to increase performance and reduce damage. [ABSTRACT FROM AUTHOR]

The urea–creatinine ratio (UCR) has been proposed as potential biomarker for critical illness-associated catabolism. Its role in the context of aneurysmal subarachnoid hemorrhage (aSAH) remains to be elucidated, which was the aim of the present study. We enrolled 66 patients with aSAH with normal renal function and 36 patients undergoing elective cardiac surgery as a control group for the effects of surgery. In patients with aSAH, the predictive or diagnostic value of early (day 0–2) and critical (day 5–7) UCRs was assessed with regard to delayed cerebral ischemia (DCI), DCI-related infarction, and clinical outcome after 12 months. Preoperatively, UCR was similar both groups. Within 2 days postoperatively, UCRs increased significantly in patients in the elective cardiac surgery group (P < 0.001) but decreased back to baseline on day 5–7 (P = 0.245), whereas UCRs in patients with aSAH increased to significantly greater levels on day 5–7 (P = 0.028). Greater early or critical UCRs were associated with poor clinical outcomes (P = 0.015) or DCI (P = 0.011), DCI-related infarction (P = 0.006), and poor clinical outcomes (P < 0.001) respectively. In multivariate analysis, there was an independent association between greater early UCRs and poor clinical outcomes (P = 0.026). In this exploratory study of UCR in the context of aSAH, greater early values were predictive for a poor clinical outcome after 12 months, whereas greater critical values were associated with DCI, DCI-related infarctions, and poor clinical outcomes. The clinical implications as well as the pathophysiologic relevance of protein catabolism should be explored further in the context of aSAH. [ABSTRACT FROM AUTHOR]

Background: Muscle atrophy is a common pathology associated with disuse, such as prolonged bed rest or spaceflight, and is associated with detrimental health outcomes. There is emerging evidence that disuse atrophy may differentially affect males and females. Cellular mechanisms contributing to the development and progression of disuse remain elusive, particularly protein turnover cascades. The purpose of this study was to investigate the initial development and progression of disuse muscle atrophy in male and female mice using the well‐established model of hindlimb unloading (HU). Methods: One hundred C57BL/6J mice (50 male and 50 female) were hindlimb suspended for 0 (control), 24, 48, 72, or 168 h to induce disuse atrophy (10 animals per group). At designated time points, animals were euthanized, and tissues (extensor digitorum longus, gastrocnemius, and soleus for mRNA analysis, gastrocnemius and extensor digitorum longus for protein synthesis rates, and tibialis anterior for histology) were collected for analysis of protein turnover mechanisms (protein anabolism and catabolism). Results: Both males and females lost ~30% of tibialis anterior cross‐sectional area after 168 h of disuse. Males had no statistical difference in MHCIIB fibre area, whereas unloaded females had ~33% lower MHCIIB cross‐sectional area by 168 h of unloading. Both males and females had lower fractional protein synthesis rates (FSRs) within 24–48 h of HU, and females appeared to have a greater reduction compared with males within 24 h of HU (~23% lower FSRs in males vs. 40% lower FSRs in females). Males and females exhibited differential patterns and responses in multiple markers of protein anabolism, catabolism, and myogenic capacity during the development and progression of disuse atrophy. Specifically, females had greater mRNA inductions of catabolic factors Ubc and Gadd45a (~4‐fold greater content in females compared with ~2‐fold greater content in males) and greater inductions of anabolic inhibitors Redd1 and Deptor with disuse across multiple muscle tissues exhibiting different fibre phenotypes. Conclusions: These results suggest that the aetiology of disuse muscle atrophy is more complicated and nuanced than previously thought, with different responses based on muscle phenotypes and between males and females, with females having greater inductions of atrophic markers early in the development of disuse atrophy. [ABSTRACT FROM AUTHOR]

Abstract Background A strain of Leghorn chickens (rd/rd), unable to produce a functional riboflavin-binding protein, lays riboflavin-deficient eggs, in which all embryos suddenly die at mid-incubation (days 13-15). This malady, caused by riboflavin deficiency, leads to excessive lipid accumulation in liver, impaired β-oxidation of lipid, and severe hypoglycemia prior to death. We have used high-density chicken microarrays for time-course transcriptional scans of liver in chicken embryos between days 9-15 during this riboflavin-deficiency-induced metabolic catastrophe. For comparison, half of rd/rd embryos (n = 16) were rescued from this calamity by injection of riboflavin just prior to incubation of fertile eggs from rd/rd hens. Results No significant differences were found between hepatic transcriptomes of riboflavin-deficient and riboflavin-rescued embryos at the first two ages (days 9 and 11). Overall, we found a 3.2-fold increase in the number of differentially expressed hepatic genes between day 13 (231 genes) and day 15 (734 genes). Higher expression of genes encoding the chicken flavoproteome was more evident in rescued- (15 genes) than in deficient-embryos (4 genes) at day 15. Diminished activity of flavin-dependent enzymes in riboflavin-deficient embryos blocks catabolism of yolk lipids, which normally serves as the predominant source of energy required for embryonic development. Conclusions Riboflavin deficiency in mid-stage embryos leads to reduced expression of numerous genes controlling critical functions, including β-oxidation of lipids, blood coagulation and feathering. Surprisingly, reduced expression of feather keratin 1 was found in liver of riboflavin-deficient embryos at e15, which could be related to their delayed feathering and sparse clubbed down. A large number of genes are expressed at higher levels in liver of riboflavin-deficient embryos; these up-regulated genes control lipid storage/transport, gluconeogenesis, ketogenesis, protein catabolism/ubiquitination and cell death.

Proteins serve a range of physiological functions in health and in disease. Their overall structure is determined predominantly by the sequence of amino acids when they are synthesized, which in turn is a derivative of the sequence of nucleotides in the corresponding segment of DNA. There is a constant turnover of body protein, the rate of which exceeds dietary protein intake and therefore suggests a degree of recycling. Some amino acids that enter the body protein pool can be synthesized ('non-essential' amino acids) while others can only be obtained through dietary means ('essential' amino acids). During critical illness and significant trauma there appears to be dysregulation such that synthesis of some non-essential amino acids is limited, while there is an increase in amino acid oxidation. Modification of dietary intake to address the potential imbalance in illness is probably insufficient in isolation to prevent muscle wasting. [ABSTRACT FROM AUTHOR]

Activation of the mechanistic target of rapamycin (mTOR) pathway is known to promote protein synthesis by enhancing mRNA translation. However, there have been few literatures on the effect of mTOR on protein metabolism in non-mammals. The main source of ammonia in fish comes from protein catabolism. The key step of protein catabolism involves the deamination and/or transamination of amino acids. This study is aimed to explore the mechanism underlying mTOR pathway influencing protein retention from the perspective of protein catabolism. Chinese perch were fasted for 24 h and divided into 4 groups randomly before intracerebroventricular (ICV) injection: (1) control group for leucine; (2) leucine group; (3) control group for leucine and rapamycin; (4) leucine and rapamycin group. Food intake was equivalent between each control and treatment groups at each time point (0.5, 4, 12 and 24 h post-injection). Ammonia-N excretion rate, blood glucose, S6 phosphorylation level, and expression of relative genes of protein catabolism (GDH, AMPD, AST, ALT) were determined. The results indicated that the pS6 level was increased, and that the ammonia-N excretion rate, blood glucose, and mRNA level of protein catabolism genes (GDH and AMPD) were significantly decreased after injection with leucine, while those changes were reversed after injection with leucine and rapamycin. Our study not only reveals the mechanism by which mTOR mediates protein synthesis by inhibiting protein catabolism in Chinese perch, but also provides reference for improving the utilization of feed protein. • mTOR inhibited protein catabolism. • mTOR inhibited deamination to decrease ammonia-N excretion.Leucine activated mTOR in Chinese perch. [ABSTRACT FROM AUTHOR]

Insulin resistance is a uniform reaction in critically ill patients. Its accompanying phenomena are hyperglycemia and protein catabolism, which are generally associated with deleterious effects on the body. The efforts to influence insulin resistance have so far been ineffective in critically ill patients. The aim of this work is to give an overview of the current state of knowledge about the causes and consequences of insulin resistance in critically ill patients and describe the current possibilities of influencing catabolic processes. [ABSTRACT FROM AUTHOR]

• Metabolic responses of heat-stressed dairy cows have not been fully elucidated. • The milk metabolome revealed altered amino acid metabolism during heat stress. • Vitamin E/Se supplementation attenuated muscle catabolism in heat stress. • No significant effects of high vitamin D 3 /Ca were observed on the metabolome. • Diets with levels of vitamin E/Se above recommendations should be further evaluated. Our understanding of metabolic alterations triggered by heat stress is incomplete, which limits the designing of nutritional strategies to mitigate negative productive and health effects. Thus, this study aimed to explore the metabolic responses of heat-stressed dairy cows to dietary supplementation with vitamin D 3 /Ca and vitamin E/Se. Twelve multiparous Holstein cows were enrolled in a split-plot Latin square design with two distinct vitamin E/Se supplementation levels, either at a low (ESe− , n = 6, 11.1 IU/kg vitamin E and 0.55 mg/kg Se) or a high dose (ESe+ , n = 6 223 IU/kg vitamin E and 1.8 mg/kg Se) as the main plot. Treatment subplots, arranged in a replicated 3 × 3 Latin square design, comprised heat challenge (Temperature Humidity Index, THI : 72.0–82.0) supplemented with different levels of vitamin D 3 /Ca: either low (HS/DCa −, 1 012 IU/kg and 0.73%, respectively) or high (HS/DCa+, 3 764 IU/kg and 0.97%, respectively), and a pair-fed control group in thermoneutrality (THI = 61.0–64.0) receiving the low dose of vitamin D 3 /Ca (TN). The liquid chromatography-mass spectrometry-based metabolome profile was determined in blood plasma and milk sampled at the beginning (day 0) and end (day 14) of each experimental period. The results were analyzed for the effect of (1) TN vs. HS/ESe−/DCa−, and (2) the vitamin E/Se and vitamin D 3 /Ca supplementation. No group or group × day effects were detected in the plasma metabolome (false discovery rate, FDR > 0.05), except for triglyceride 52:2 being higher (FDR = 0.03) on day 0 than 14. Taurine, creatinine and butyryl-carnitine showed group × day interactions in the milk metabolome (FDR ≤ 0.05) as creatinine (+22%) and butyryl-carnitine (+190%) were increased (P < 0.01) on day 14, and taurine was decreased (−65%, P < 0.01) on day 14 in the heat stress (HS) cows, compared with day 0. Most compounds were unaffected by vitamin E/Se or vitamin D 3 /Ca supplementation level or their interaction (FDR > 0.05) in plasma and milk, except for milk alanine which was lower (−69%, FDR = 0.03) in the E/Se+ groups, compared with E/Se−. Our results indicated that HS triggered more prominent changes in the milk than in the plasma metabolome, with consistent results in milk suggesting increased muscle catabolism, as reflected by increased creatinine, alanine and citrulline levels. Supplementing with high levels of vitamin E/Se or vitamin D 3 /Ca or their combination did not appear to affect the metabolic remodeling triggered by HS. [ABSTRACT FROM AUTHOR]

Introduction: Diabetes Mellitus includes a group of prevalent metabolic (metabolism) disorders which may occur in fat and protein metabolism. According to the research of specialists, regular exercise is essential to control and improve diabetes. Therefore, this study was performed with aim to evaluate the effect of circadian rhythm during 12 weeks of aerobic exercise on protein catabolism of type 2 diabetic women. Methods: This semi-experimental study was conducted on 45 women with diabetes in Behbahan at 20116. They were randomly divided into two experimental groups (n=15 in each group) of aerobic training in morning and afternoon and control group. The experimental group underwent selective aerobic exercise with the intensity of 55-70%, the maximum heart beat and the increasing time of 35-50 minutes per session. The activity intensity was added up to 5% every four weeks. After 15 minutes of walking briskly, the exercise included aerobics and coordinated movements of hands and feet. The control group didn’t have exercise during 12 weeks. 24 hour urine urea test was measured and assessed in the first and 12th week. Data was analyzed by SPSS Software (version 16) and ANOVA and LSD tests. P

Low protein diets (LPs) constitute a reportedly effective form of nutritional therapy for canine chronic kidney disease and cirrhosis. These diets have long been feared to result in reduced muscle mass due to protein catabolism. This adverse effect, however, remains largely unrecognized in veterinary medicine as there are no easily applicable catabolism indicators. Therefore, we focused on urinary creatinine, a metabolite of protein in the urine, and examined whether its ratio to urinary urea nitrogen (UCrn/UN) can be used to assess protein catabolism. In Experiment 1, we first consecutively fed seven healthy beagles an LP, standard protein (SP), and high protein (HP) diet for 1 week each and then measured the UCrn/UN ratio at 2-h intervals from fasting to 16 h post-prandially. We consequently found that the UCrn/UN ratio was significantly elevated in the LP pre-prandially and at all post-prandial measurement points (P < 0.01). No significant differences were observed between the SP and HP. Analysis of fasting plasma amino-acid concentrations revealed that the concentration of methionine was significantly lower in the LP than in the other diets (P < 0.05). Although the effects of this change in amino-acid concentration were unclear, the UCrn/UN ratio was considered having increased due to a deficiency in protein and/or amino acids during LP feeding. In Experiment 2, we continuously fed five healthy beagles an LP for 18 weeks and then measured the UCrn/UN ratio as described above. We also measured changes in body composition with computed tomography. At weeks 10 and 18, the fasting UCrn/UN ratio was significantly higher than it was prior to the start of the LP; however, post-prandially, the UCrn/UN ratio decreased to the point that the significant difference disappeared. Muscle mass decreased at weeks 10 and 18. These results suggest that the fasting UCrn/UN ratio could be used as an indicator of protein catabolism in LP feeding. Our experiments thus indicate that examination of potential increases in the UCrn/UN ratio 1 week after introduction of LP feeding to healthy dogs could enable detection of body protein catabolism in long-term feeding of LP before muscle breakdown occurs.

Acute elevation of cortisol via activation of the hypothalamic-pituitary-interrenal (HPI) axis aids the fish in dealing with a stressor. However, chronic elevation of cortisol has detrimental effects and has been studied extensively in lab settings. However, data pertaining to wild teleosts are lacking. Here, we characterized the metabolic consequences of prolonged cortisol elevation (96 h) in wild-caught pumpkinseed (Lepomis gibbosus). Pumpkinseed were implanted with cocoa butter alone (sham) or containing cortisol (25 mg kg−1 body weight), and at 24, 48, 72, and 96 h, tissue samples were collected, whole-body ammonia excretion was determined, and whole-organism metabolism was assessed using intermittent flow respirometry. Cortisol-treated pumpkinseed exhibited the highest plasma cortisol concentration at 24 h post-implantation, with levels decreasing over the subsequent time points although remaining higher than in sham-treated fish. Cortisol-treated fish exhibited higher standard and maximal metabolic rates than sham-treated fish, but the effect of cortisol treatment on aerobic scope was negligible. Indices of energy synthesis/mobilization, including blood glucose concentrations, hepatosomatic index, hepatic glycogen concentrations, and ammonia excretion rates, were higher in cortisol-treated fish compared with controls. Our work suggests that although aerobic scope was not diminished by prolonged elevation of cortisol levels, higher metabolic expenditures may be of detriment to the animal's performance in the longer term. [ABSTRACT FROM AUTHOR]

Migratory birds use protein as a fuel source during flight, but the mechanisms and benefits of protein catabolism during migration are poorly understood. The tissue-specific turnover rate hypothesis proposes that lean mass loss depends solely on the constitutive rate of protein degradation for a given tissue, and is therefore independent of metabolic rate or environmental stimuli. However, it has been demonstrated that environmental stressors such as humidity affect the rate of lean mass catabolism during flight, a finding that seemingly contradicts the tissue-specific turnover rate hypothesis. In order to resolve this, we placed migratory Swainson's thrushes in either high (HEWL) or low (LEWL) evaporative water loss conditions at rest and while undergoing simulated migratory flight at 8 m s−1 in a wind tunnel to test the impact of both environmental stressors and metabolic rate on the rate of protein breakdown. The total quantity and rate of lean mass loss was not different between flight and rest birds, but was affected by humidity condition, with HEWL losing significantly more lean mass. These results show that the rate of protein breakdown in migratory birds is independent of metabolic rate, but it can be augmented in response to environmental stressors. [ABSTRACT FROM AUTHOR]

Hyperammonaemia and hyperethanolaemia are thought to be driving factors behind skeletal muscle myopathy in liver disease, that is, cirrhosis. Despite this, the singular and combined impacts of ethanol‐ and ammonia‐induced protein catabolism are poorly defined. As such, we aimed to dissect out the effects of ammonia and ethanol on muscle catabolism. Murine C2C12 myotubes were treated with ammonium acetate (10 mM) and ethanol (100 mM) either alone or in combination for 4 hr and/or 24 hr. Myotube diameter, muscle protein synthesis and anabolic and catabolic signalling pathways were assessed. In separate experiments, cells were cotreated with selected inhibitors of protein breakdown to assess the importance of proteolytic pathways in protein loss with ammonia and ethanol. Ammonia and ethanol in combination resulted in a reduction in myotube width and total protein content, which was greater than the reduction observed with ammonia alone. Both ammonia and ethanol caused reductions in protein synthesis, as assessed by puromycin incorporation. There was also evidence of impairments in regulation of protein translation, and increased protein expression of markers of muscle protein breakdown. Myotube protein loss with ammonia plus ethanol was not affected by autophagy inhibition, but was completely prevented by proteasome inhibition. Thus, combined ammonia and ethanol incubation of C2C12 myotubes exacerbated myotube atrophy and dysregulation of anabolic and catabolic signalling pathways associated with either component individually. Ubiquitin proteasome‐mediated protein breakdown appears to play an important role in myotube protein loss with ethanol and ammonia. The findings from this study indicate that a combination of ammonia and ethanol incubation of C2C12 myotubes exacerbated muscle atrophy and dysregulation of anabolic and catabolic signalling pathways associated with either component individually. Our findings provide novel insight into the interactions between hyperammonaemia and hyperethanolaemia in relation to their regulation of muscle catabolism in vitro. [ABSTRACT FROM AUTHOR]

Background: The optimal amount of protein intake in critically ill patients is uncertain. Objective: In this post hoc analysis of the PermiT (Permissive Underfeeding vs. Target Enteral Feeding in Adult Critically Ill Patients) trial, we tested the hypothesis that higher total protein intake was associated with lower 90-d mortality and improved protein biomarkers in critically ill patients. Design: In this post hoc analysis of the PermiT trial, we included patients who received enteral feeding for =3 consecutive days. Using the median protein intake of the cohort as a cutoff, patients were categorized into 2 groups: a higher-protein group (>0.80 g · kg-1 · d-1) and a lower-protein group (=0.80 g · kg-1 · d-1). We developed a propensity score for receiving higher protein. Primary outcome was 90-d mortality. We also compared serial values of prealbumin, transferrin, 24-h urinary nitrogen, and 24-h nitrogen balance on days 1, 7, and 14. Results: Among the 729 patients included in this analysis, the average protein intake was 0.8 ± 0.3 g · kg-1 · d-1 [1.0 ± 0.2 g · kg-1 · d-1 in the higher-protein group (n = 365) and 0.6 ± 0.2 g · kg-1 · d-1 in the lower-protein group (n = 364); P < 0.0001]. There was no difference in 90-d mortality between the 2 groups [88/364 (24.2%) compared with 94/363 (25.9%), propensity score-adjusted OR: 0.80; 95% CI: 0.56, 1.16; P = 0.24]. Higher protein intakewas associated with an increase in 24-h urea nitrogen excretion compared with lower protein intake, but without a significant change in prealbumin, transferrin, or 24-h nitrogen balance. Conclusions: In the PermiT trial, a moderate difference in protein intake was not associated with lower mortality. Higher protein intake was associated with increased nitrogen excretion in the urine without a corresponding change in prealbumin, transferrin, or nitrogen balance. Protein intake needs to be tested in adequately powered randomized controlled trials targeting larger differences in protein intake in high-risk populations. [ABSTRACT FROM AUTHOR]

Insulin and nutrients have profound effects on proteome homeostasis. Currently no reliable methods are available to measure postprandial protein turnover. A triple-tracer method was developed using phenylalanine stable isotope tracers to estimate appearance rates of ingested (Ra meal) and endogenous phenylalanine and the rate of phenylalanine disposal (Rd). This was compared with the "traditional" dual-tracer method, using one (1-CM)- and two (2-CM)-compartment models. For both methods, [13C6]phenylalanine was given orally, and [15N]phenylalanine was constantly infused; the triple-tracer method added [2H5]phenylalanine, infused at rates to mimic meal [13C6]phenylalanine appearance. Additionally, incorporation of mealderived phenylalanine into specific proteins was measured after purification by two-dimensional electrophoresis. The triple-tracer approach reduced modeling errors, allowing improved reconstruction of Ra meal with a tracer-to-tracee ratio that was more constant and better estimated Rd. The 2-CM better described phenylalanine kinetics and Rd than 1-CM. Thus, the triple-tracer approach using 2-CM is superior for measuring non-steady-state postprandial protein turnover. This novel approach also allows measurement of postprandial synthesis rates of specific plasma proteins. We offer a valid non-steady-state model to measure postprandial protein turnover and synthesis of plasma proteins that can safely be applied in adults, children, and pregnant women. [ABSTRACT FROM AUTHOR]

The use of fat to support the energy needs of reproduction (i.e. capital breeding) has been studied in a diversity of taxa. However, despite reproductive output (i.e. young or eggs) being approximately 70% water, little is known about the availability of internal resources to accommodate the hydric demands of reproduction. Recent research suggests that dehydration increases the catabolism of muscle as a means of maintaining water balance. Accordingly, we investigated the interactive effects of reproductive investment and water deprivation on catabolism and reproductive output in female Children's pythons (Antaresia childreni). Both reproductive and nonreproductive females were either provided water ad libitum or were water-deprived for three weeks at the time when reproductive females were gravid. We found that water-deprived reproductive females had, in general, greater body mass loss, epaxial muscle loss, plasma osmolality and plasma uric acid concentrations relative to the other groups. Furthermore, water-deprived females had similar clutch sizes compared with females with access to water, but produced lighter eggs and lower total clutch masses. Our results provide the first evidence that selective protein catabolism can be used to support water demands during reproduction, and, as a result, these findings extend the capital breeding concept to non-energetic resources. [ABSTRACT FROM AUTHOR]

Proteins serve a range of physiological functions in health and in disease. Their overall structure is determined predominantly by the sequence of amino acids when they are synthesized, which in turn is a derivative of the sequence of nucleotides in the corresponding segment of DNA. There is a constant turnover of body protein, the rate of which exceeds dietary protein intake and therefore suggests a degree of recycling. Some amino acids that enter the body protein pool can be synthesized (‘non-essential’ amino acids) while others can only be obtained through dietary means (‘essential’ amino acids). During critical illness and significant trauma there appears to be dysregulation such that synthesis of some non-essential amino acids is limited, while there is an increase in amino acid oxidation. Modification of dietary intake to address the potential imbalance in illness is probably insufficient in isolation to prevent muscle wasting. [ABSTRACT FROM AUTHOR]