Body Protein Catabolism Research Articles

Plasma Metabolite Profiles Between In-Center Daytime Extended-Hours and Conventional Hemodialysis.

Protein-energy wasting, characterized by disordered body protein catabolism resulting from metabolic and nutritional derangements, is associated with adverse clinical outcomes in patients undergoing hemodialysis. Extended-hours hemodialysis (≥6 h per treatment session) offers both enhanced removal of uremic solutes and better fluid management, generally allowing more liberalized dietary protein and calorie intake. This study aimed to evaluate the difference in plasma metabolite profiles among patients receiving in-center daytime extended-hours hemodialysis and those receiving conventional hemodialysis. Pre-dialysis plasma samples were obtained from 188 patients on extended-hours hemodialysis (21.9 h/week) and 286 patients on conventional hemodialysis (12.1 h/week) in Japan in 2020 using capillary electrophoresis-mass spectrometry. Group differences were compared for 117 metabolites using Wilcoxon rank-sum tests with multiple comparisons and partial least squares discriminant analysis. Additionally, propensity score-adjusted multiple regression analyses were performed to evaluate group differences for known uremic toxins, branched-chain amino acids, and lactate-to-pyruvate ratio (a possible surrogate marker of mitochondrial dysfunction). Significant differences were observed in 39 metabolites, largely consistent with the high variable importance for prediction in partial least squares discriminant analysis. Among known uremic toxins, uridine and hypoxanthine levels were significantly higher in the conventional hemodialysis group than in the extended-hours hemodialysis group, whereas trimethylamine N-oxide levels were higher in the extended-hours hemodialysis group than in the conventional hemodialysis group. Patients on extended-hours hemodialysis had higher levels of all branched-chain amino acids and a lower lactate-to-pyruvate ratio than those on conventional hemodialysis (significant difference of -8.6 [95% confidence interval, -9.8 to -7.4]). Extended-hours hemodialysis was associated with a more favorable plasma metabolic and amino acid profile; however, concentrations of most uremic toxins did not significantly differ from those of conventional hemodialysis.

70 Nutrient Restriction During Late Gestation Alters Maternal Circulating Amino Acid Concentrations in Primiparous Beef Females

Abstract We hypothesized that maternal circulating AA concentrations would be reduced by late gestational nutrient restriction, indicating less available nutrients for transport by the uteroplacenta to the growing fetus. Fall-calving Hereford-SimAngus heifers [single-sired; BW: 451 ± 28 (SD) kg; BCS: 5.4 ± 0.7] bred to a single sire were allocated by fetal sex and expected calving date to receive either 100% (control; CON; n = 12) or 70% (NR; n = 13) of NASEM metabolizable energy and metabolizable protein requirements for maintenance, pregnancy, and growth from day 160 of gestation to calving. Heifers were individually fed chopped sorghum sudan hay (1.74 Mcal ME, 6.66% CP, 72.0% NDF; DM basis) and based on individual intakes, supplemented to meet targeted nutritional planes. Jugular blood samples were obtained on days 159 (Pre-treatment), 202, and 244 of gestation, and 1 h post-calving to determine serum concentrations of the 20 common AA (except cysteine), 1-methyl histidine, and 3-methyl histidine. Gestational and post-calving AA were analyzed separately with nutritional plane, treatment initiation date, and calf sex (when P < 0.25) as fixed effects. Gestational AA included day and nutritional plane x day using repeated measures. We have previously reported that dam BCS was less (P ≤ 0.04) by day 202 of gestation and dam BW was less (P ≤ 0.01) by day 223 of gestation for NR dams. Post-calving, NR dams were 64 kg BW and 2.0 BCS lless (P < 0.001), but calf birth weight was not affected (P = 0.72) by nutritional plane. Histidine, lysine, and methionine were greater (P ≤ 0.03) in NR dams on day 202 of gestation. Tryptophan and valine were less (P ≤ 0.05) while methionine and total AA tended to be less (P ≤ 0.08) on day 244 of gestation in NR dams. Aspartic acid, glutamic acid, and tyrosine were less (P ≤ 0.03), but 3-methyl histidine was greater (P ≤ 0.01) on days 202 and 244 of gestation in NR dams. 1-methyl histidine was greater (P ≤ 0.05) at all 3 gestational timepoints but leucine was less (P = 0.03) in NR dams during gestation. Post-calving, glutamic acid, leucine, and valine were less (P ≤ 0.04), and methionine, threonine, tryptophan, tyrosine, and total AA tended to be less (P ≤ 0.10) in NR dams. Histidine, 1-methyl histidine, 3-methyl histidine, and serine were greater (P ≤ 0.03) in NR dams post-calving. In summary, late gestational nutrient restriction reduced total maternal circulating AA and altered the maternal serum AA profile, but calf birth weight was not affected. Individual AA that were greater or unaffected in NR dams were likely indicative of body protein catabolism occurring to meet nutrient requirements.

Feed restriction as a tool for further studies describing the mechanisms underlying lipolysis in milk in dairy cows

Milk lipolysis is defined as the hydrolysis of triglycerides, which are the main component of milk fat. Short-chain fatty acids (FAs) released in milk are responsible for rancid flavour. In addition, the presence of partial glycerides impairs the functional properties of milk, such as foaming and creaming abilities. Milk lipolysis, a key criterion used to assess milk quality, depends on animal parameters and breeding factors. Low-energy diets are associated with higher levels of spontaneous lipolysis, particularly in late lactation. In this study, dairy cows were fed a restricted diet (i.e. 65% of their ad libitum DM intake (DMI)) to induce spontaneous lipolysis in milk and to study milk composition associated with lipolysis. Two groups of 22 cows each received a control diet (100% of ad libitum DMI) or the restricted diet according to a 2 × 2 crossover design. The restricted diet was fed for five days. As expected, feed restriction increased milk spontaneous lipolysis which was associated with an increase in lipoprotein lipase activity. At the same time, milk yield and protein content decreased and no effect was observed on milk fat content. The increase in spontaneous lipolysis was associated with an increase in milk fat globules diameter, without influencing casein micelles diameter. Feed restriction altered the parameters of dairy cow metabolism, with increases in plasma non-esterified FAs, triglycerides and urea, indicating body fat mobilisation and protein catabolism associated with feed restriction. Feed restriction also altered hormonal parameters, with decreases in plasma insulin, insulin-like growth factor 1 and prolactin. As expected, lipolysis was higher in evening milk and was associated with a larger diameter of milk fat globules. This zootechnical approach will be completed with proteomic, lipidomic and transcriptomic studies of milk and/or mammary gland of animals selected for their extreme lipolysis.

Updated Concepts in Perioperative Nutrition

Despite the awareness of the prevalence of malnutrition in patients scheduled for major GI surgery, and its association with increased morbidity and mortality, as well as increased cost of care, perioperative nutrition is still underutilized as a strategy to improve surgical outcomes.
 Following the deliberately inflicted trauma of major surgery, a neuroendocrine response stimulates mobilization of energy reserves from the liver that are transiently available for up to 3 days. Beyond this, the body will then turn to whole body protein catabolism for substrates. This loss of lean body mass is potentially harmful and has been observed as a loss of muscle mass in the diaphragm, the psoas muscles, or the thigh. Further, it has been shown that when the magnitude of loss of muscle mass reaches 20%, it is associated with decreased wound healing, increased muscle weakness, and increased risk of infection.

POS-241 FRAILTY: COROLLARY OR CAUSALITY OF MALNUTRITION

Frailty is a composite assessment usually used in elderly population for evaluating their overall general health. Studies show that frail individuals have a poor survival and increased morbidity. Chronic kidney disease (CKD) is chronic inflammatory state and closely related to frailty due to various reasons like hormonal changes, anorexia, decreased muscle strength and depression. Malnutrition or PEW (Protein energy wasting) in CKD occurs due to various reasons that increase the body protein catabolism along with the rate of muscle degradation.

A Novel Approach for Managing Protein-Energy Wasting in People With Kidney Failure Undergoing Maintenance Hemodialysis: Rationale and Call for Trials

Protein-energy wasting (PEW) is a unique presentation of protein-energy malnutrition in people with kidney disease that is characterized by body protein catabolism exceeding anabolism. PEW is especially common in patients undergoing maintenance hemodialysis (HD) treatment. Dietary guidelines for managing PEW in HD patients primarily focus on protein adequacy and typically promote the intake of animal-based protein foods. Although intake of protein and essential amino acids is important for protein synthesis, the emphasis on protein adequacy largely fails to address-and may actually exacerbate-many of the root causes of PEW. This perspective examines the dietary determinants of PEW in people undergoing HD treatment, with an emphasis on upstream disease-related factors that reduce dietary protein utilization and impair dietary intakes. From this, we present a theoretical diet model for managing PEW that includes etiology-based dietary strategies to address barriers to intake and treat disease-related factors, as well as supportive dietary strategies to promote adequate energy and protein intakes. Given the complexity of diet-disease interactions in the pathogenesis of PEW, and its ongoing burden in HD patients, interventional trials are urgently needed to evaluate alternative diet therapy approaches for PEW in this population.

112 Young Scholar Presentation: Protein and Amino Acid Nutrition in Fresh Cows

Abstract During the 4 weeks after parturition, postpartum dairy cows (i.e., fresh cows) have the highest risk of disease and metabolic disorders. This is largely because nutrient requirements for lactation outweigh the cow’s metabolizable intake. As a result, cows enter negative nutrient balances and mobilize endogenous protein and energy stores to meet demands. Although negative energy balance, in terms of mass, is more negative than protein balances over this time frame, intake of metabolize protein (MP) and its amino acid (AA) profile may influence the performance and health of fresh cows more than increasing energy intake. Better performance from greater MP and AA supplies may also carry over and enhance milk production further into lactation. In our recent experiment, increasing MP supplies to fresh cows by feeding a greater rumen undegradable protein concentration (RUP; 7 vs 10% of DM) also increased milk and milk component yields. However, when the AA profile of the supplemental RUP was optimized to mimic the AA profile of casein, the greater yields were sustained much further into lactation. This may be because fresh cows fed the “casein like AA profile” had improved health and less body protein catabolism than cows fed a similar MP concentration. However, production responses with a greater MP intake depended on what the RUP replaced in the diet and on parity. When replacing forage fiber with RUP instead of nonforage fiber, multiparous cows had a reduction in milk and milk fat yields whereas primiparous cows performed similarly regardless of what type fiber was replaced. This suggested reducing forage fiber in a high MP diet will not increase overall MP intake, and multiparous cows may require more forage fiber during the fresh period than primiparous cows. Overall, MP intake and the AA supply is important for the health and production of fresh cows.

Usefulness of Urinary Creatinine/Urea Nitrogen Ratio as Indicator of Body Protein Catabolism in Dogs Fed Low Protein Diets.

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.

The preliminary analysis of protein catabolism and nitrogen balance in young gymnasts

Summary Objectives The use of proper diet in athletes is one of the most important elements of sports training. Moreover, the essentials in planning diet for athletes among other things should be taken into account: energy balance, the nutritional value of meals and supplements of diet. The main aim of this study was to estimate the level of whole body proteins catabolism, nitrogen and energy balance in young gymnasts. Methods In the present study participated young gymnastics (13.0 ± 0.5 year), which have been trained artistic gymnastics since 6.8 ± 0.45 year. The investigation contained two times measuring urea in 24 h urine collection, measuring energy expenditure indirect method by 24 h monitoring heart rate, and supplementation by 7 days products contain protein and carbohydrate. Results Concentration of urea nitrogen in urine at the first test before supplementation was 8.0 ± 0.75 g/d. The energy expenditure in young boys before supplementation was negative (−915 ± 130 kcal). The concentration of urea nitrogen was lower in 4 out of 5 examined boys as compared to the first test after supplementation. The difference between the level of nitrogen balance output and the level after supplementation was statistically significant (P ≤ 0.05). Conclusion The supplementation with proteins and carbohydrates products immediately after training may lead to decrease concentration of urea nitrogen and whole body protein catabolism. Monitoring energy expenditure, food nutrients, and calories in diet during and after training should be an integral part of planning for long-term training program.

Nutrition and immune system disorders

Energy and nutrients obtained through food play an important role in the development and preservation of the immune system therefore any nutritional imbalance affects its competence and integrity. Knowing the nutritional approach on different disorders of the immune system. A review has been carried out on the most prevalent immunological disorders in developed countries, the nutritional characteristics to which they are associated and their nutritional approach. Nutritional treatment for immune disorders has focused in recent years on the role of PUFA-ω3 and vitamin D. Maintaining body weight, preventing malnutrition and protein catabolism are key strategies for nutritional treatment. This should be adapted to each disease stage because it is a dynamic process. Nutritional treatment for immunological disorders, especially in autoimmune diseases, is not always clear because they present acute and remission states. Anorexia is one of the most characteristic symptoms derived mainly from pharmacological treatment and inflammatory processes. Diet should be dense in nutrients that prevent deterioration.Nutritional treatment of immunological disorders should aim to maintain an optimal state of nutrition during symptomatic periods, prevent their deterioration during acute episodes and improve during stable periods free of symptoms.

PT03.2: High Intensity Resistance Exercise Induces Whole Body Protein Catabolism in Patients with Chronic Obstructive Pulmonary Disease

PT03.2: High Intensity Resistance Exercise Induces Whole Body Protein Catabolism in Patients with Chronic Obstructive Pulmonary Disease

Response to nutritional support and therapeutic approaches of amino acid and protein metabolism in surgical patients

The response to critical illness involves alterations in all aspects of metabolic control, favoring catabolism of body protein. In particular, body protein loss occurring as a result of the alteration of protein metabolism has been reported to be inversely correlated with the survival of critically ill patients. Despite the availability of various therapeutic modalities aiming to prevent loss of the body protein pool, such as total parenteral nutrition, enteral nutrition designed to provide excessive calories as a form of energy substrate, and protein itself, the loss of body protein cannot be prevented by any of these. Loss of the boyd protein store occurs as a consequence of the alteration of the intermediate metabolism that works for the production of energy substrate. This alteration of substrate metabolism may be linked to the alteration of protein metabolism. However, no specific factors regulating amino acid and protein metabolism have been identified. Thus, further investigations evaluating amino acid and protein metabolism are required to obtain better understanding of metabolic regulation in the body, which may lead to the development of novel and more effective therapeutic modalities for nutrition in the future.

Thoracic Epidural Analgesia and Acute Pain Management

AIN continues to be a significant problem for many patients after major surgery. In addition to improving patient satisfaction and decreasing pain scores, enhanced perioperative pain control can improve clinical outcomes. Thoracic epidural analgesia (TEA) remains a critical tool for anesthesiologists to use in acute pain management. TEA is particularly effective for reducing pain after thoracic and upper abdominal surgery and likely permits major surgical procedures to be performed on patients with moderate to severe comorbid diseases, who several years ago may have been determined to be too great a risk for surgery. In the past 10 yr, peripheral nerve blockade has improved perioperative analgesia for patients undergoing extremity surgery. Although nerve blocks have reduced the use of continuous lumbar epidural analgesia, anesthesiologists must understand the indications, placement techniques, solutions administered, potential complications, and evidence-based outcomes for TEA in acute pain management. Indications

House sparrows (Passer domesticus) increase protein catabolism in response to water restriction

Birds primarily rely on fat for energy during fasting and to fuel energetically demanding activities. Proteins are catabolized supplemental to fat, the function of which in birds remains poorly understood. It has been proposed that birds may increase the catabolism of body protein under dehydrating conditions as a means to maintain water balance, because catabolism of wet protein yields more total metabolic and bound water (0.155·H(2)O(-1)·kJ(-1)) than wet lipids (0.029 g·H(2)O(-1)·kJ(-1)). On the other hand, protein sparing should be important to maintain function of muscles and organs. We used quantitative magnetic resonance body composition analysis and hygrometry to investigate the effect of water restriction on fat and lean mass catabolism during short-term fasting at rest and in response to a metabolic challenge (4-h shivering) in house sparrows (Passer domesticus). Water loss at rest and during shivering was compared with water gains from the catabolism of tissue. At rest, water-restricted birds had significantly greater lean mass loss, higher plasma uric acid concentration, and plasma osmolality than control birds. Endogenous water gains from lean mass catabolism offset losses over the resting period. Water restriction had no effect on lean mass catabolism during shivering, as water gains from fat oxidation appeared sufficient to maintain water balance. These data provide direct evidence supporting the hypothesis that water stress can increase protein catabolism at rest, possibly as a metabolic strategy to offset high rates of evaporative water loss.

Surplus dietary tryptophan inhibits stress hormone kinetics and induces insulin resistance in pigs

Recently we have shown that surplus dietary tryptophan (TRP) reduced the plasma concentrations of cortisol and noradrenaline in pigs. Stress hormones are known to affect insulin sensitivity and metabolism. We now investigated the long-term effects of surplus dietary TRP on 1) plasma and urinary stress hormone kinetics, 2) insulin sensitivity for glucose and amino acid clearance, and 3) whole body nitrogen balance. Pigs were fed for 3 weeks a high (13.2%) vs normal (3.4%) TRP to large neutral amino acids (LNAA) diet, leading to reduced fasting (14 h) plasma cortisol (17.1 ± 3.0 vs 28.9 ± 4.3 ng/mL, p < 0.05) and noradrenaline (138 ± 14 vs 225 ± 21 pg/mL, p < 0.005) concentrations, lower daily urinary noradrenaline (313 ± 32 vs 674 ± 102 ng/kg day, p < 0.001) and adrenaline (124 ± 13 vs 297 ± 42 ng/kg day, p < 0.001) but higher dopamine (5.8 ± 0.5 vs 1.5 ± 0.2 µg/kg day, p < 0.001) excretions, respectively. Insulin sensitivities for both glucose and amino acid clearance, (as measured by the intraportal hyperinsulinaemic (1 mU/kg min) euglycaemic euaminoacidaemic clamp technique), were lower by 22% in pigs on the high vs normal TRP/LNAA diet (14.8 ± 1.4 vs 18.9 ± 0.9, p < 0.05 and 69.7 ± 4.3 vs 89.7 ± 6.8 mL/kg min, p < 0.05, respectively) without affecting urinary nitrogen excretion (35.5 ± 1.0 vs 36.6 ± 1.0% of dietary nitrogen intake, p = ns). In conclusion, long-term feeding of surplus dietary TRP inhibits both baseline adrenocortical and sympathetic nervous system activity, it induces insulin resistance for both glucose and amino acid clearance but it does not affect whole body protein catabolism. This indicates that the bioactive amino acid TRP contributes to homeostasis in neuroendocrinology and insulin action and that low baseline adrenocortical and sympatho-adrenal axis activity are associated with insulin resistance.

Metabolic consequences of body size and body composition in hemodialysis patients

Small body mass index is associated with increased mortality in chronic hemodialysis patients. The reasons for this observation are unclear but may be related to body composition. This study aimed to investigate the body composition in chronic hemodialysis patients. The difference between body mass and the sum of muscle, bone, subcutaneous, and visceral adipose tissue masses, measured by whole body magnetic resonance imaging, was defined as the high metabolic rate compartment representing the visceral mass. Protein catabolic rate was calculated from urea kinetics. Forty chronic hemodialysis patients (mean age 54.7 years; 87.5% African Americans; 45% females) were studied. High metabolic rate compartment expressed in percent of body weight was inversely related to body weight (r=-0.475; P=0.002) and body mass index (r=-0.530; P<0.001). In a multiple linear regression model, protein catabolic rate was significantly correlated only with high metabolic rate compartment (r=0.616; P<0.001). Assuming that protein catabolic rate in addition to protein intake reflects urea and uremic toxin generation, it follows that high metabolic rate compartment is the major compartment involved in their generation. Consequently, uremic toxin production rate may be relatively higher in patients with low body weight and low body mass index as compared to their heavier counterparts. The poorer survival observed in smaller dialysis patients may be related to these relative differences.

Beneficial effect of amino acid supplementation, especially cysteine, on body nitrogen economy in septic rats

Muscle wasting and increased synthesis of proteins and compounds involved in host defense characterize severe injury. The aims of the studies reported were to determine which amino acids exhibited an increased tissue content linked to anabolic processes in infected rats by comparison with healthy pair-fed controls, and to explore whether diets supplemented with these amino acids attenuate the catabolic response to infection. Total amino acid content of the liver and the rest of the body were measured in control well-fed rats, in infected rats and their pair-fed controls 2 days after infection. In the nutritional protocols, infected rats were fed with a diet supplemented with alanine (basal diet), or threonine, serine, aspartate, asparagine and arginine (AA) or AA+cysteine (complete diet). Infection significantly increased liver total amino acid content by 38% for most amino acids. In contrast, the percentage increase was cysteine 79.3, threonine 45.3, aspartate-asparagine 46.3 and serine 46.5. Whole body without liver content of most amino acids decreased after infection due to the catabolic response, while the content of cysteine increased by 6% (P<0.05) and those of threonine and arginine did not decrease. After infection, animals fed the complete diet lost less weight than animals fed the basal diet (P<0.05). Furthermore, AA plus cysteine supplementation reduced significantly urinary nitrogen excretion and muscle wasting. The results provide evidence that diet supplementation with cysteine, threonine, serine, aspartate-asparagine and arginine supports the synthesis of vital proteins to spare body protein catabolism during infection.

Tolerance for Branched-Chain Amino Acids in Experimental Animals and Humans

There is no good evidence for establishing branched-chain amino acid (BCAA) tolerance levels for humans. With pigs, chicks, and rats, data are available concerning excessive intake levels of BCAA, but most of the information is for growing animals instead of for adults. Estimates of maintenance requirements for (high-quality) protein and BCAA in pigs weighing between 43 and 140 kg are 350 mg . kg(-1) . d(-1) for protein and 28.7 mg . kg(-1) . d(-1) for total BCAA. In contrast, human adult maintenance requirement estimates are much higher, i.e., 660 mg . kg(-1) . d(-1) for good quality protein and a range of 68 to 144 mg . kg(-1) . d(-1) for total BCAA. The human maintenance BCAA requirement estimates range from 10.3 to 22% of the maintenance protein requirement. Whole-body protein of 45-kg pigs contains 14.2 g BCAA/100 g protein, but the maintenance requirement (based on nitrogen balance) for total BCAA is only 8.2% of the total maintenance protein requirement. Conversely, sulfur amino acid (methionine + cysteine), threonine, and tryptophan maintenance requirements of pigs as a percentage of the maintenance protein requirement are much higher than whole-body protein levels of these amino acids. This suggests that the efficiency of using absorbed amino acids of dietary origin or of reusing endogenous amino acids arising from body protein catabolism may vary considerably among the indispensable amino acids. Additionally, work with pigs points to the conclusion that whole-body amino acid concentrations are poor predictors of both maintenance requirements and ideal amino acid profiles. Based on studies with young experimental animals, a rather large dietary excess (above requirement) of an individual BCAA is well tolerated when consumed in diets containing surfeit levels of protein and the other 2 BCAA.

Hypoenergetic High-Carbohydrate or High-Fat Parenteral Nutrition Induces a Similar Metabolic Response with Differential Effects on Hepatic IGF-I mRNA in Dexamethasone-Treated Rats

The optimal level of energy for critically ill patients who require parenteral nutrition (PN) is unclear. Our objective was to determine whether 50% energy (50%E) restriction due to a reduction in carbohydrate or fat, with provision of adequate protein and micronutrients, ameliorates the detrimental effects of dexamethasone (Dex) on body protein catabolism, insulin resistance, and insulin-like growth factor-I (IGF-I) responses in rats administered PN. The experiment included 6 PN groups, adequate energy (AE) +/- Dex, 50% AE with high carbohydrate (50%E CHO) +/- Dex and 50% AE with high fat (50%E FAT) +/- Dex. There was a significant interaction between energy level and Dex such that the increase in body catabolism due to 50%E from CHO or FAT was reduced by approximately 50%, although the amount of body weight and nitrogen lost over 7 d was significantly greater with 50%E than with AE. AE+Dex induced a 60% increase in liver mass, whereas 50%E+Dex reduced the increase to 26%. AE+Dex induced a 5-fold increase in serum insulin level, whereas 50%E+Dex normalized the insulin to glucose ratio. Serum IGF-I levels were reduced 14-18% by Dex and 30% by 50%E. Hepatic immunoreactive IGF-I was significantly correlated with serum IGF-I and nitrogen balance. 50%E CHO and 50%E FAT had differential effects on hepatic IGF-I mRNA with a 40% decrease in IGF-I mRNA due to 50%E FAT+Dex. In summary,CHO or FAT hypoenergetic PN with adequate protein had similar effects in normalizing hyperinsulinemia, attenuating hepatomegaly, and reducing the increment, but not the total amount of body protein catabolism, induced by glucocorticoid excess.

Glutamine kinetics and protein turnover in end-stage renal disease.

Alanine and glutamine constitute the two most important nitrogen carriers released from the muscle. We studied the intracellular amino acid transport kinetics and protein turnover in nine end-stage renal disease (ESRD) patients and eight controls by use of stable isotopes of phenylalanine, alanine, and glutamine. The amino acid transport kinetics and protein turnover were calculated with a three-pool model from the amino acid concentrations and enrichment in the artery, vein, and muscle compartments. Muscle protein breakdown was more than synthesis (nmol.min(-1).100 ml leg(-1)) during hemodialysis (HD) (169.8 +/- 20.0 vs. 125.9 +/- 21.8, P < 0.05) and in controls (126.9 +/- 6.9 vs. 98.4 +/- 7.5, P < 0.05), but synthesis and catabolism were comparable pre-HD (100.7 +/- 15.7 vs. 103.4 +/- 14.8). Whole body protein catabolism decreased by 15% during HD. The intracellular appearance of alanine (399.0 +/- 47.1 vs. 243.0 +/- 34.689) and glutamine (369.7 +/- 40.6 vs. 235.6 +/- 27.5) from muscle protein breakdown increased during dialysis (nmol.min(-1).100 ml leg(-1), P < 0.01). However, the de novo synthesis of alanine (3,468.9 +/- 572.2 vs. 3,140.5 +/- 467.7) and glutamine (1,751.4 +/- 82.6 vs. 1,782.2 +/- 86.4) did not change significantly intradialysis (nmol.min(-1).100 ml leg(-1)). Branched-chain amino acid catabolism (191.8 +/- 63.4 vs. -59.1 +/- 42.9) and nonprotein glutamate disposal (347.0 +/- 46.3 vs. 222.3 +/- 43.6) increased intradialysis compared with pre-HD (nmol.min(-1).100 ml leg(-1), P < 0.01). The mRNA levels of glutamine synthase (1.45 +/- 0.14 vs. 0.33 +/- 0.08, P < 0.001) and branched-chain keto acid dehydrogenase-E2 (3.86 +/- 0.48 vs. 2.14 +/- 0.27, P < 0.05) in the muscle increased during HD. Thus intracellular concentrations of alanine and glutamine are maintained during HD by augmented release of the amino acids from muscle protein catabolism. Although muscle protein breakdown increased intradialysis, the whole body protein catabolism decreased, suggesting central utilization of amino acids released from skeletal muscle.