Albumin Fractional Synthesis Rate Research Articles

A novel dynamic proteomics approach for the measurement of broiler chicken protein fractional synthesis rate.

The study of protein synthesis in farm animals is uncommon despite its potential to increase knowledge about metabolism and discover new biomarkers of health and growth status. The present study describes a novel dynamic proteomics approach for the measurement of protein fractional synthesis rate (FSR) in broiler chickens. Chickens received a 10g/kg oral dose of 2 H2 O at day 21 of their life. Body water 2 H abundance was measured in plasma samples using a portable Fourier transform infrared spectrometer. Free and protein-bound amino acids (AAs) were isolated and had their 2 H enrichment measured by gas chromatography with mass spectrometry (GC/MS). Peptide 2 H enrichment was measured by proteomics analysis of plasma and muscle samples. Albumin, fibrinogen and muscle protein FSR were calculated from GC/MS and proteomics data. Ala appeared to be more enriched at the site of protein synthesis than in the AA free pools. Glu was found to be the AA closest to isotopic equilibrium between the different AA pools. Glu was used as an anchor to calculate n(AA) values necessary for chicken protein FSR calculation in dynamic proteomics studies. FSR values calculated using proteomics data and GC/MS data showed good agreement as evidenced by a Bland-Altman residual plot. A new dynamic proteomics approach for the measurement of broiler chicken individual protein FSR based on the administration of a single 2 H2 O oral bolus has been developed and validated. The proposed approach could facilitate new immunological and nutritional studies on free-living animals.

Effects of amino acids and albumin administration on albumin metabolism in surgically stressed rats: A basic nutritional study.

Nutrition therapy and administration of albumin preparations are common in postsurgical patients. However, the effects of these interventions on albumin metabolism are unclear. We elucidated the effect of postoperative albumin and/or parenteral nutrition administration on it. Sprague-Dawley rats underwent surgery involving intestinal rubbing followed by intestinal exposure. Subsequently, they were administered experimental solutions for 48 h, their blood samples were collected at 24 and 48 h, and livers were excised at 48 h. Based on experimental solutions, rats were divided into five groups: non-surgical (Non-surg); glucose and electrolyte solution (GE); amino acid, glucose, and electrolyte solution (AGE); GE + rat serum albumin (Alb) (GE + Alb); and AGE + Alb. Their plasma albumin concentrations; albumin fractional synthesis rate (ALB FSR); mercaptoalbumin/total albumin ratio (MA ratio); and messenger RNA (mRNA) expressions of albumin and hepatocyte nuclear factor-1 (HNF-1) in the liver were measured. The GE and AGE groups showed significant decline in albumin concentrations. ALB FSR was significantly enhanced in the AGE group compared with the GE group. The mRNA expression of albumin was similar to ALB FSR in all groups and that of HNF-1 was significantly decreased in the GE + Alb and AGE + Alb groups compared with the Non-surg group. The MA ratio in the AGE group was similar to the Non-surg group. The administration of amino acids comprising parenteral nutrition after surgery augmented ALB FSR and maintained the MA ratio only without simultaneous albumin administration.

The fractional synthesis rates of plasma proteins as determined using deuterated water are sensitive to dietary intake of lysine in rats.

Traditionally, the effect of dietary lysine upon health is determined through the concentrations of plasma proteins, but sometimes they are not responsive to lysine intake. We hypothesized that the fractional synthesis rates (FSRs) of plasma proteins may be more sensitive to dietary intake of lysine than protein concentrations in plasma. Seventy-two male Sprague-Dawley rats were divided randomly into three groups based on their diets provided for 18weeks: low lysine (LG), normal lysine (NG) and high lysine (HG). Rats underwent labeling with deuterated water, a more reliable tracer than amino-acid tracers. The FSRs of albumin and immunoglobulin (Ig) G in plasma increased with increasing dietary intake of lysine. However, the albumin concentration in plasma in rats in the LG did not decrease significantly compared with that in the NG, and a similar result was shown for the IgG concentration between the NG and HG. These results suggested that the FSRs of albumin and IgG in plasma were more sensitive to dietary intake of lysine than their concentrations, and could be useful as sensitive indicators of the effect of dietary lysine upon health.

Impact of 3-week citrulline supplementation on postprandial protein metabolism in malnourished older patients: The Ciproage randomized controlled trial

Citrulline (CIT), is not extracted by the splanchnic area, can stimulate muscle protein synthesis and could potentially find clinical applications in conditions involving low amino acid (AA) intake, such as in malnourished older subjects. Our purpose was to research the effects of CIT supplementation on protein metabolism in particular on non-oxidative leucine disposal (NOLD, primary endpoint), and splanchnic extraction of amino acids in malnourished older patients. This prospective randomized multicenter study determined whole-body and liver protein synthesis, splanchnic protein metabolism and appendicular skeletal muscle mass (ASMM) in 24 malnourished older patients [80-92 years; 18 women and 6 men] in inpatient rehabilitation units. All received an oral dose of 10g of CIT or an equimolar mixture of six non-essential amino acids (NEAAs), as isonitrogenous placebo, for 3 weeks. NOLD and albumin fractional synthesis rates were not different between the NEAA and CIT groups. Splanchnic extraction of dietary amino acid tended to decrease (p=0.09) in the CIT group (45.2%) compared with the NEAA group (60.3%). Total differences in AA and NEAA area under the curves between fed-state and postabsorptive-state were significantly higher in the CIT than in the NEAA group. There were no significant differences for body mass index, fat mass (FM), lean mass (LM) or ASMM in the whole population except for a tendential decrease in FM for the citrulline group (p=0.089). Compared with Day 1, lean mass and ASMM significantly increased (respectively p=0.016 and p=0.018) at Day 20 in CIT-treated women (mean respective increase of 1.7kg and 1.1kg), and fat mass significantly decreased (p=0.001) at Day 20 in CIT-group women (mean decrease of 1.3kg). Our results demonstrate that CIT supplementation has no effect on whole-body protein synthesis or liver protein synthesis in malnourished older subjects. However, CIT supplementation was associated with a higher systemic AA availability. In the subgroup of women, CIT supplementation increased LM and ASMM, and decreased FM.

Repeated quantitative measurements of De Novo synthesis of albumin and fibrinogen.

The possibility of using two different isotopomers, for the incorporation of isotopically labeled amino acids, was explored to enable longitudinal studies of de novo synthesis of two export liver proteins, albumin and fibrinogen. The agreement of the synthesis rates between the two different labels was evaluated along with the reproducibility of repeated experiments using different time intervals. Healthy volunteers were studied in a standardized fed state. Protocol A (n = 10) involved two measurements 48 hours apart. Protocol B (n = 6) involved three measurements at baseline and five hours and then seven days after the initial measurement. De novo synthesis of albumin and fibrinogen by the incorporation of D5-phenylalanine or D8-phenylalanine were measured using the flooding dose technique. Albumin and fibrinogen were isolated from plasma using standard techniques. Fractional and absolute synthesis rates were calculated. Repeated measurements employing the two isotoptomers showed good agreement for albumin fractional synthesis rate after 48 hours (p = 0.92) and after 7 days (p = 0.99), with a coefficient of variation of 5.9% when using the same isotopic label. For fibrinogen, the coefficient of variation for the fractional synthesis rate employing the same isotopic label was 16.6%. Repeated measurements after 48 hours and seven days showed less agreement although there was no statistical difference (P = 0.32 and P = 0.30 respectively). Repeated measurement after five hours showed a statistical significant difference for the fractional synthesis rate of fibrinogen (p = 0.008) but not for albumin (p = 0.12). Repeated measurements of albumin de novo synthesis more than 48 hours apart show acceptable agreement using either one or two different isotopic labels. For fibrinogen the larger intra-individual scatter necessitates larger study groups to detect changes in longitudinal studies. Repeated measurements within 48 hours need to be validated further.

The reduced/oxidized state of plasma albumin is modulated by dietary protein intake partly via albumin synthesis rate in rats

The reduced/oxidized state of plasma albumin is influenced by many factors, including chronic diseases and strenuous training. Recently, the reduced/oxidized state has also been shown to be associated with dietary protein and energy intakes in rats. We hypothesized that dietary protein intake may modulate the reduced/oxidized state of plasma albumin by altering the rate of albumin synthesis and that the reduced/oxidized state could therefore serve as a novel marker of protein undernutrition. We tested this hypothesis by examining male growing rats placed on a low-protein or energy-restriction diet. In the 4-week experiment, animals fed a low-protein diet (3% casein), whose dietary intakes were lower than those fed control diet (20% casein), showed significant decreases in plasma albumin level and the ratio of the reduced form of albumin to total albumin. Animals given the same amount of control diet as the low-protein diet group (approximately 30% energy restriction) also showed the above decreases, albeit to much more limited extents. The ratio of reduced to total plasma albumin correlated significantly with plasma albumin fractional synthesis rate. When animals were maintained on the low-protein diet for as long as 12 weeks and then fed the control diet for 1 week, the decreased ratio of reduced to total plasma albumin, but not plasma albumin level, resolved rapidly. The reduced/oxidized state of plasma albumin would thus reflect dietary protein status via plasma albumin turnover including the fractional synthesis rate and could prove useful as a sensitive marker of protein undernutrition.

Metabolism of albumin after continuous venovenous hemofiltration in patients with systemic inflammatory response syndrome.

Background. The systemic inflammatory response syndrome (SIRS) is characterized by a hypercatabolic state induced by inflammatory mediators. Continuous venovenous hemofiltration (CVVH) stabilizes the internal environment but also aggravates loss of amino acids. The effect of CVVH on protein dynamics is largely unknown. We adopted the stable isotopic tracer technology to investigate how CVVH changed serum albumin metabolism. Methods. Twenty SIRS patients were randomized into low- (2000 mL/h) and high- (4000 mL/h) volume CVVH groups according to the rate of replacement fluid. Eight patients with abdominal infection matched for age, sex, and laboratory index served as controls. Consecutive arterial blood samples were drawn during a primed-constant infusion of two stable isotopes to determine the albumin fractional synthesis rate (FSR) and fractional breakdown rate (FBR). Results. Before treatment, there was no significant difference of FSR and FBR among 3 groups. After CVVH, the albumin FSR in high- and low-volume groups was 7.75 ± 1.08% and 7.30 ± 0.89%, respectively, both higher than in the control (5.83 ± 0.94%). There was no significant difference in albumin FBR after treatment. Conclusions. Protein dynamic indicators could reflect protein synthesis and breakdown state directly and effectively. CVVH increased albumin synthesis, while the breakdown rate remained at a high level independently of the CVVH rate.

Dynamics of Albumin Synthetic Response to Intra-Abdominal Abscess in Patients with Gastrointestinal Fistula

Low serum albumin concentration is a predictor of failure of source control for intra-abdominal infection. However, data on dynamics of albumin synthesis in these patients and to what extent these changes contribute to hypoalbuminemia are relatively scarce. We investigated in a group of patients with gastrointestinal fistula the dynamic response of liver albumin synthesis to intra-abdominal abscess and how these related to hypoalbuminemia and circulating endocrine hormone profiles. Eight gastrointestinal fistula patients scheduled to undergo percutaneous abscess sump drainage were enrolled prospectively to measure albumin synthesis rates at different stages of the inflammatory response (immediately after diagnosis and 7 d following sump drainage when clinical signs of intra-abdominal sepsis had been eradicated). Eight age-, sex-, and body mass index-matched intestinal fistula patients were studied as control patients. Consecutive arterial blood samples were drawn during a primed-constant infusion (priming dose: 4 micromol·kg(-1), infusion rate: 6 micromol·kg(-1)·min(-1)) to determine the incorporation rate of L-[ring-(2)H5]-phenylalanine directly into plasma albumin using gas chromatography/mass spectrometry analysis. Patients suffering from intra-abdominal infection had reduced plasma albumin and total plasma protein concentrations, compared with control patients. Albumin fractional synthesis rates in patients with intra-abdominal abscess were decreased, compared with those in the control group. When the source of infection was removed, albumin synthesis rates returned to control values, whereas albumin concentrations did not differ significantly from the corresponding concentrations in control subjects and patients with intra-abdominal abscess. Despite nutritional intervention, albumin synthesis rate is decreased in intestinal fistula patients with intra-abdominal abscess; albumin synthesis returns to control values during convalescence.

Restricting sulfur amino acid intake in growing pigs challenged with lipopolysaccharides decreases plasma protein and albumin synthesis

Litvak, N., Htoo, J. K. and de Lange, C. F. M. 2013. Restricting sulfur amino acid intake in growing pigs challenged with lipopolysaccharides decreases plasma protein and albumin synthesis. Can. J. Anim. Sci. 93: 505–515. Chronic subclinical levels of disease occur frequently in swine production and compromise nutrient utilization efficiency. Methionine and cysteine (M+C) are involved in the pig's response to immune system stimulation (ISS), acting as substrates for the synthesis of compounds involved in the immune response, such as acute phase proteins (APP). This study was conducted to determine the impact of ISS with lipopolysaccharide (LPS) and M+C intake (high vs. low; 4.0 vs. 2.2 g d−1) on the fractional synthesis rate (FSR) of plasma albumin and fibrinogen, as well as protein in plasma and various tissues of starter pigs. Fifteen pigs (9.8±1.4 kg body weight) were allotted to one of three treatments: (1) Control (LPS− and high M+C), (2) LPS+ and high M+C, or (3) LPS+ and low M+C. Pigs were given intramuscular injections of increasing doses of LPS 1 and 3 d before determining FSR using an intravenous infusion of a flooding dose of L-[ring−1H5]-phenylalanine. Plasma levels of APP were not affected by the LPS challenge (P>0.10); only plasma albumin levels decreased with reduced M+C intake (P=0.02). Total plasma protein FSR was increased during the LPS challenge (50.3 vs. 56.9% d−1, SEM = 1.6; P=0.01). Albumin FSR was not affected by an LPS challenge (P>0.10), but decreased with reduced M+C intake during the LPS challenge (49.5 vs. 41.9% d−1, SEM = 1.6; P=0.005). Spleen protein FSR tended to increase during the LPS challenge (P=0.08). There were no treatment effects on protein FSR in liver, small intestine, loin or plasma fibrinogen (P>0.10). Restricting M+C intake during a LPS challenge decreases albumin synthesis and tends to reduce plasma protein synthesis, implicating M+C as important nutrients involved in the immune response.

Protein Redistribution From Skeletal Muscle to Splanchnic Tissue on Fasting and Refeeding in Young and Older Healthy Individuals

During aging, a shift of protein metabolism from muscle to splanchnic tissue contributes to increased muscle protein loss after a period of metabolic stress (eg, fasting). To study the adaptation of protein metabolism in the whole body and tissue (ie, skeletal muscle and splanchnic area) to metabolic stress, such as short-term fasting and refeeding, in aged people. We studied splanchnic and muscle protein metabolism after 38 hours of fasting and refeeding in 7 young (5 men/2 women, 24.4 ± 2.0 years) and 8 elderly individuals (6 men/2 women, 70.6 ± 3.1 years). We used intravenous (IV) L-[(13)C6]phenylalanine, IV L-[(2)H3]leucine, and oral L-[(13)C1]leucine to obtain (1) whole-body protein kinetics, (2) muscle and albumin fractional synthesis rate (FSR, %/d; (13)C6-Phe, and (13)C1-Leu), and (3) splanchnic extraction during fasting and refeeding (%, (2)H3- and (13)C1-Leu). Whole-body protein breakdown was activated during fasting in young and older individuals (P<.01 vs fasted state). Muscle FSR remained unchanged in both groups and not stimulated by refeeding in either group with either IV (13)C Phe or oral (13)C Leu, probably because of high plasma levels of essential amino acids (EAAs) and branched-chain amino acids (BCAAs). Splanchnic extraction of leucine was 42% higher in the elderly individuals (P= .03 vs young) and was associated with an increased albumin synthesis rate in elderly individuals in the fed state (P < .05 vs young). Splanchnic protein metabolism is modified by age, but this metabolic change is not associated with a lower synthesis rate of muscle protein, provided high plasma levels of essential EAAs are maintained. Our data also suggest that splanchnic protein synthesis is a metabolic priority during recovery after metabolic stress in healthy elderly persons and that it might be even more affected in polymedicated older individuals having chronic diseases.

Moderate hyperglycemia and a blunted anabolic response to perioperative parenteral amino acids in type 2 diabetes mellitus patients undergoing colorectal cancer surgery

Insulin resistance of type 2 diabetes mellitus (T2DM) is accentuated by surgical stress. Hyperglycemia can also be exacerbated by nutrition support; so a balance of anabolic and euglycemic strategies is essential. Patients with T2DM (n=7) or without (ND, n=11) undergoing colorectal cancer surgery received parenteral nutrition (PN) based on 20% of resting energy expenditure as amino acids (AAs, from 20h preop). Glucose, protein kinetics and fractional synthesis rate (FSR) of hepatic secretory proteins were measured with D‐[6,6‐2H2] glucose, L‐[1‐13C]leucine and L‐[ring‐2H5]phenylalanine while fasting preop, and again while receiving PN two days postop. In fasted state preop, subjects were in negative leucine balance, with T2DM being more negative than ND (p&lt;0.027). PN improved leucine balance (p=0.008), but balance was more negative in T2DM. Surgery invoked an acute phase response with increased fibrinogen (p&lt;0.0001) and its FSR (p&lt;0.0007). Albumin FSR was maintained to a similar extent postop. Plasma glucose was similar preop, but higher postop in T2DM (p&lt;0.005), possibly resulting from a tendency for higher endogenous production (p&lt;0.10) and lower clearance (p&lt;0.13). Plasma AAs showed changes typical of surgery attenuated increases in branched chains (p=0.035) and essentials (p=0.026) in T2DM. PN with AAs supports acute phase response in T2DM but with moderate hyperglycemia and a blunted anabolic response. Higher AA doses or combined AA and low glucose are suggested achieve anabolic response in T2DM.(Canadian Institutes of Health Research)

Dietary protein regulates hepatic constitutive protein anabolism in rats in a dose-dependent manner and independently of energy nutrient composition

We had previously observed that drastic increases in protein consumption greatly modified hepatic protein anabolism in rats, but the confounding effects of other macronutrient changes or a moderate protein increase to generate the same modifications have not yet been established. This study examined the metabolic and hormonal responses of rats subjected to 14-day isoenergetic diets containing normal, intermediate, or high-protein levels (NP: 14% of energy, IP: 33%, HP: 50%) and different carbohydrate (CHO) to fat ratios within each protein level. Fasted or fed rats (n = 104) were killed after the injection of a flooding dose of (13)C-valine. The hepatic protein content increased in line with the dietary protein level (P < 0.05). The hepatic fractional synthesis rates (FSR) of protein were significantly influenced by both the protein level and the nutritional state (fasted vs. fed) (P < 0.0001) but not by the CHO level, reaching on average 110%/day, 92%/day, and 83%/day in rats fed the NP, IP, and HP diets, respectively. The FSR of plasma albumin and muscle did not differ between diets, while feeding tended to increase muscle FSR. Proteolysis, especially the proteasome-dependent system, was down-regulated in the fed state in the liver when protein content increased. Insulin decreased with the CHO level in the diet. Our results reveal that excess dietary protein lowers hepatic constitutive, but not exported, protein synthesis rates, independently of the other macronutrients, and related changes in insulin levels. This response was observed at the moderate levels of protein intake (33%) that are plausible in a context of human consumption.

Does Increasing Blood pH Stimulate Protein Synthesis in Dialysis Patients?

Background: Although the mechanism of muscle wasting in end-stage renal disease is not fully understood, there is increasing evidence that acidosis induces muscle protein degradation and could therefore contribute to the loss of muscle protein stores of patients on hemodialysis, a prototypical state of chronic metabolic acidosis (CMA). Because body protein mass is controlled by the balance between synthesis and degradation, protein loss can occur as result of either increased breakdown, impaired synthesis, or both. Correction of acidosis may therefore help to maintain muscle mass and improve the health of patients with CMA. We evaluated whether alkalizing patients on hemodialysis might have a positive effect on protein synthesis and on nutritional parameters. Methods: Eight chronic hemodialysis patients were treated daily with oral sodium bicarbonate (NaHCO₃) supplementation for 10–14 days, yielding a pre-dialytic plasma bicarbonate concentration of 28.6 ±1.6 mmol/l. The fractional synthesis rates (FSR) of muscle protein and albumin were obtained by the L-[²H₅ring]phenylalanine flooding technique. Results: Oral NaHCO₃supplementation induced a significant increase in serum bicarbonate (21.5 ± 3.4 vs. 28.6 ± 1.6 mmol/l; p = 0.018) and blood pH (7.41 vs. 7.46; p = 0.041). The FSR of muscle protein and the FSR of albumin did not change significantly (muscle protein: 2.1 ± 0.2 vs. 2.0 ± 0.5% per day, p = 0.39; albumin: 8.3 ± 2.2 vs. 8.6 ± 2.5% per day, p = 0.31). Plasma concentrations of insulin-like growth factor 1 decreased significantly (33.4 ± 21.3 vs. 25.4 ± 12.3 nmol/l; p = 0.028), whereas thyroid-stimulating hormone, free thyroxin and free triiodothyronine did not change significantly and nutritional parameters showed no improvement. Conclusion: In contrast to other findings, raising the blood pH of dialysis patients was not associated with a positive effect on albumin and muscle protein synthesis, or nutritional and endocrinal parameters.

Interleukin-6 modulates hepatic and muscle protein synthesis during hemodialysis

Increased demand for amino acids to sustain acute-phase protein synthesis could be the stimulus for the increased muscle protein catabolism during hemodialysis (HD). This could be attenuated by intradialytic amino-acid infusion. To test this, we measured the fractional synthesis rates of albumin, fibrinogen, and muscle protein in eight patients with end-stage renal disease at baseline before dialysis and during HD without or with amino-acid infusion. The percentage change in the fractional synthesis rates of albumin, fibrinogen, and muscle protein from baseline was significantly higher during HD with amino-acid infusion than without amino-acid infusion. Leg muscle proteolysis was significantly increased during unsupplemented HD compared with baseline, but this was not decreased by amino-acid infusion. Arteriovenous balance studies across the leg showed a net efflux of interleukin-6 (IL-6) from the muscle into the vein during HD. The fractional synthesis rate of albumin, fibrinogen, and muscle protein correlated with each other and with the IL-6 efflux from the leg. Leg muscle protein catabolism was positively related to IL-6 release from the leg and not associated with amino-acid availability. Our results show that intradialytic cytokine activation and not amino-acid depletion is the major protein catabolic signal during HD.

Dietary protein intake affects albumin fractional synthesis rate in younger and older adults equally

Inclusion of dietary protein in meals and beverages affects the hepatic synthesis of the protein albumin. Besides dietary protein, several factors can influence albumin metabolism and affect plasma albumin. The role of aging in albumin synthesis is unclear. Recent research documents that albumin synthesis rate is influenced comparably in younger and older adults by dietary protein ingestion and changes in dietary protein quantity. This emphasizes the importance for all adults to consume an adequate amount of dietary protein.

Effects of dietary protein restriction on albumin and fibrinogen synthesis in macroalbuminuric type 2 diabetic patients

Diabetic nephropathy is associated with hypoalbuminaemia and hyperfibrinogenaemia. A low-protein diet has been recommended in patients with diabetic nephropathy, but its effects on albumin and fibrinogen synthesis are unknown. We compared the effects of a normal (NPD; 1.38 +/- 0.08 g kg(-1) day(-1)) or low (LPD; 0.81 +/- 0.04 g kg(-1) day(-1)) -protein diet on endogenous leucine flux (ELF), albumin and fibrinogen synthesis (L-[5,5,5,-2H3]leucine infusion), and markers of inflammation in nine type 2 diabetic patients with macroalbuminuria. Six healthy participants on NPD served as control participants. In comparison with healthy participants, type 2 diabetic patients on an NPD had similar ELF, reduced serum albumin (38 +/- 1.1 vs 42 +/- 0.8 g/l; p < 0.05), similar fractional synthesis rates (FSR) and absolute synthesis rates (ASR) of albumin, and both increased plasma fibrinogen concentration [10.7 +/- 0.6 vs 7.2 +/- 0.5 micromol/l (3.64 +/- 0.22 vs 2.45 +/- 0.18 g/l); p < 0.05] and fibrinogen ASR [11.03 +/- 1.17 vs 6.0 +/- 1.8 micromol 1.73 m(-2) day(-1) (3.7 +/- 0.4 vs 1.9 +/- 0.3 g 1.73 m(-2) day(-1)); p < 0.01]. After LPD, type 2 diabetic patients had the following changes in comparison with NPD: reduced proteinuria (2.74 +/- 0.4 vs 4.51 +/- 0.8 g/day; p < 0.05), ELF (1.93 +/- 0.08 vs 2.11 +/- 0.08 micromol kg(-1) min(-1); p < 0.05) and total fibrinogen pool; increased serum albumin (42 +/- 1 vs 38 +/- 1 g/l; p < 0.01) and albumin ASR (14.1 +/- 1 vs 9.9 +/- 1 g 1.73 m(-2) day(-1); p < 0.05); and reduced plasma IL-6 levels, which were correlated with albumin ASR (r = -0.749; p < 0.05). LPD in type 2 diabetic patients with diabetic nephropathy reduces low-grade inflammatory state, proteinuria, albuminuria, whole-body proteolysis and ASR of fibrinogen, while increasing albumin FSR, ASR and serum concentration.

Albumin synthesis in premature neonates is stimulated by parenterally administered amino acids during the first days of life

Background: We recently showed that parenteral administration of amino acids to premature infants immediately after birth is safe and results in a positive nitrogen balance and increased whole-body protein synthesis. However, we did not determine organ-specific effects; albumin, produced by the liver, is an important protein, but its concentration is often low in premature neonates during the first few days after birth.Objective: The objective of the study was to test the hypothesis that the fractional and absolute albumin synthesis rates would increase with the administration of amino acids after birth, even at low nonprotein energy intake.Design: Premature infants (<1500 g birth weight), who were on ventilation, received from birth onward either glucose only (control group, n = 7) or glucose and 2.4 g amino acid · kg−1 · d−1 (intervention group, n = 8). On postnatal day 2, all infants received a primed continuous infusion of [1-13C]leucine, and mass spectrometry techniques were used to determine the incorporation of the leucine into albumin. Results are expressed as medians and 25th and 75th percentiles.Results: Albumin fractional synthesis rates in the intervention group were significantly higher than those in the control group [22.9% (17.6–28.0%)/d and 12.6% (11.0–19.4%)/d, respectively; P = 0.029]. Likewise, the albumin absolute synthesis rates in the intervention group were significantly higher than those in the control group [228 (187–289) mg · kg−1 · d−1 and 168 (118–203) mg · kg−1 · d−1, respectively; P = 0.030].Conclusion: Amino acid administration increases albumin synthesis rates in premature neonates even at a low energy intake.

Nutrient Ingestion, Protein Intake, and Sex, but Not Age, Affect the Albumin Synthesis Rate in Humans 3

The aim of this study was to assess the effects of nutrient ingestion, dietary protein intake, age, and sex on the fractional synthesis rate (FSR) of albumin. Thirty-six healthy free-living individuals (8 females and 10 males aged 21–43 y and 9 females and 9 males aged 63–79 y) completed three 18-d periods of controlled feeding with protein intakes of 125% (P125, 1.00 g protein · kg−1 · d−1), 94% (P94, 0.75 g protein · kg−1 · d−1), and 63% (P63, 0.50 g protein · kg−1 · d−1) of the recommended dietary allowance. On d 12 of each trial, postabsorptive (PA) serum albumin concentration was determined and PA and postprandial (PP) albumin FSR were estimated from the rate of l-[1-13C] leucine incorporation into plasma albumin during an 8-h infusion. There were no age-related differences in PA and PP albumin FSR. Albumin FSR was higher PP than PA (P < 0.0001), and the increase in albumin FSR from PA to PP was smaller as dietary protein intake decreased from P125 to P94 and P63 (P < 0.05). Independent of protein intake, males had a higher albumin FSR (P < 0.05) and a greater increase in albumin FSR with feeding (P < 0.05). There was no age or dietary protein effect on serum albumin concentrations, but males had higher albumin concentrations than females (P < 0.0001). These results show that older persons are responsive to nutrient ingestion and dietary protein-related changes in albumin FSR. The greater albumin synthesis rate in males might contribute to a higher albumin concentration set point.

Role of ovarian hormones in the regulation of protein metabolism in women: effects of menopausal status and hormone replacement therapy

The age-related decline in fat-free mass is accelerated in women after menopause, implying that ovarian hormone deficiency may have catabolic effects on lean tissue. Because fat-free tissue mass is largely determined by its protein content, alterations in ovarian hormones would likely exert regulatory control through effects on protein balance. To address the hypothesis that ovarian hormones regulate protein metabolism, we examined the effect of menopausal status and hormone replacement therapy (HRT) on protein turnover. Whole body protein breakdown, oxidation, and synthesis were measured under postabsorptive conditions using [(13)C]leucine in healthy premenopausal (n = 15, 49 +/- 1 yr) and postmenopausal (n = 18, 53 +/- 1 yr) women. In postmenopausal women, whole body protein turnover and plasma albumin synthesis rates (assessed using [(13)C]leucine and [(2)H]phenylalanine) were also measured following 2 mo of treatment with oral HRT (0.625 mg conjugated estrogens + 2.5 mg medroxyprogesterone acetate, n = 9) or placebo (n = 9). No differences in whole body protein breakdown, oxidation, or synthesis were found between premenopausal and postmenopausal women. Protein metabolism remained similar between groups after statistical adjustment for differences in adiposity and when subgroups of women matched for percent body fat were compared. In postmenopausal women, no effect of HRT was found on whole body protein breakdown, synthesis, or oxidation. In contrast, our results support a stimulatory effect of HRT on albumin fractional synthesis rate, although this did not translate into alterations in circulating albumin concentrations. In conclusion, our results suggest no detrimental effect of ovarian hormone deficiency coincident with the postmenopausal state, and no salutary effect of hormone repletion with HRT, on rates of whole body protein turnover, although oral HRT regimens may increase the synthesis rates of albumin.

Albumin and Fibrinogen Synthesis and Insulin Effect in Type 2 Diabetic Patients With Normoalbuminuria

Insulin stimulates albumin synthesis but inhibits that of fibrinogen in both type 1 diabetic and healthy subjects. In type 2 diabetes, fibrinogen production is increased both in the postabsorptive state and in response to hyperinsulinemia. No data exist on the rate of albumin synthesis and its response to insulin in type 2 diabetes. We measured fractional synthesis rates (FSRs) and absolute synthesis rates (ASRs) of both albumin and fibrinogen in postabsorptive normoalbuminuric type 2 diabetic patients at their spontaneous glucose levels (study A), as well as albumin FSR and ASR before and after a hyperinsulinemic-euglycemic euaminoacidemic clamp (study B), using leucine isotope methods. In postabsorptive type 2 diabetes (study A), albumin FSR (11.2 +/- 0.9%/day) and albumin ASR (15.4 +/- 1.2 g/day) were not different from control values (albumin FSR: 9.4 +/- 0.7%/day; albumin ASR: 13.8 +/- 1.2 g/day, P > 0.1 for both). In contrast, in the type 2 diabetic subjects, both fibrinogen FSR (24.9 +/- 2.1%/day) and ASR (2.4 +/- 0.2 g/day) were greater (P < 0.025 and P < 0.007, respectively) compared with the control subjects (FSR: 18.6 +/- 1.51%/day; ASR: 1.6 +/- 0.2 g/day). Worse metabolic control in the type 2 diabetic patients was associated with hyperfibrinogenemia and increased leucine rate of appearance, whereas neither the (increased) fibrinogen ASR nor the (normal) albumin production was affected. In study B, after hyperinsulinemia (raised to approximately 860 nmol/l), albumin FSR and ASR increased by approximately 25% versus basal (P < 0.04) and to the same extent in both type 2 diabetic and control subjects. In normoalbuminuric type 2 diabetic patients, postabsorptive albumin synthesis and its response to insulin were normal, whereas fibrinogen synthesis was increased, irrespective of metabolic control. Furthermore, in normoalbuminuric type 2 diabetic patients, a normal insulin sensitivity with respect to albumin production but a selective hepatic dysregulation of fibrinogen metabolism were present.