Whole-body Protein Metabolism Research Articles

Level of cottonseed meal but not frequency of feeding regulates whole-body protein synthesis and growth of sheep fed a roughage diet

An incomplete factorial experiment was conducted to determine the effect of level and frequency of feeding of a protein-rich supplement on the growth and whole-body protein metabolism of young sheep fed a medium quality roughage diet. Cottonseed meal (CSM) was used as the protein supplement and provided at 0, 0.2 or 0.4% liveweight per day at a frequency of 1 or 3 times each week and chopped oaten (0.95) and lucerne (0.05) hay was the roughage. Growth rate more than doubled (P < 0.01) following provision of CSM but there was no advantage of feeding CSM at the highest level. Frequency of feeding CSM did not alter growth rate. Intake of hay was little affected by CSM and as a consequence the food conversion ratio declined (P < 0.01) favourably from 22 : 1 (nil CSM) to 9 : 1 as a result of supplementation. The rate of whole-body protein synthesis increased (P < 0.01) in response to the highest level of CSM with no apparent change in protein degradation, underpinning an increase (P < 0.01) in protein retention. These results highlight the role of protein supplements for promoting growth of young sheep on roughage diets and indicate that these supplements need to be provided only once a week.

Effect of beta-hydroxy-beta-methylbutyrate (HMB) on protein metabolism in whole body and in selected tissues

Beta-hydroxy-beta-methylbutyrate (HMB) is a leucine metabolite with protein anabolic effect. The aim of the study was to examine the role of exogenous HMB on leucine and protein metabolism in whole body and selected tissues. Rats were administered by HMB (0.1 g/kg b.w.) or by saline. The parameters of whole-body protein metabolism were evaluated 24 h later using l-[1- 14C]leucine and l-[3,4,5- 3H]phenylalanine. Changes in proteasome dependent proteolysis and protein synthesis were determined according the “chymotrypsin-like” enzyme activity and labeled leucine and phenylalanine incorporation into the protein. A decrease in leucine clearance and whole-body protein turnover (i.e., a decrease in whole-body proteolysis and protein synthesis) was observed in HMB treated rats. Proteasome-dependent proteolysis decreased significantly in skeletal muscle, changes in heart, liver, jejunum, colon, kidney, and spleen were insignificant. Decrease in protein synthesis was observed in the heart, colon, kidney, and spleen, while an increase was observed in the liver. There were no significant changes in leucine oxidation. We conclude that protein anabolic effect of HMB in skeletal muscle is related to inhibition of proteolysis in proteasome. Alterations in protein synthesis in visceral tissues may affect several important functions and the metabolic status of the whole body.

Dehydroepiandrosterone Replacement Therapy in Hypoadrenal Women: Protein Anabolism and Skeletal Muscle Function

To determine whether dehydroepiandrosterone (DHEA) replacement therapy in hypoadrenal women improves performance, muscle protein accretion, and mitochondrial functions. Thirty-three hypoadrenal women were enrolled in the study from May 1, 2002, through May 31, 2003. Twenty-eight completed a 12-week, prospective, randomized, placebo-controlled, crossover study with either daily placebo or 50 mg of DHEA with a 2-week washout period and then crossed over to the other treatment. Body composition, physical performance, whole-body and muscle protein metabolism, and mitochondrial functions were determined. Administration of DHEA significantly increased plasma levels of DHEA sulfate, testosterone, and androstenedione but did not change body composition, muscle strength, peak aerobic capacity, and whole-body protein turnover or synthesis rates of mitochondrial, sarcoplasmic, or mixed muscle proteins. Muscle mitochondrial oxidative enzymes and messenger RNA (mRNA) levels of genes encoding mitochondrial proteins and nuclear transcription factors did not change after DHEA administration. However, mRNA levels of muscle myosin heavy chain 1 (P=.004), which determines muscle fiber type, and those of insulinlike growth factor binding proteins 4 and 5 significantly decreased (P=.02 and P=.03, respectively). Three months of DHEA administration increased DHEA sulfate and androgen levels but had no effect on physical performance, body composition, protein metabolism, or muscle mitochondrial biogenesis in hypoadrenal women. However, lowering of mRNA levels of binding proteins of insulinlike growth factor 1 and myosin heavy chain 1 suggests potential effects of longterm treatment with DHEA on muscle fiber type.

Body mass index, muscle and fat in chronic kidney disease: questions about survival

The human body can be roughly divided into two major compartments, fat mass and lean body mass. Adipose tissue is now considered to be a highly active tissue and, in addition to storing calories as triglycerides, it also secretes a large variety of compounds, including cytokines, chemokines and hormone-like factors such as leptin, adiponectin and resistin. On the other hand, muscle plays a central role in whole-body protein metabolism by serving as the principal provider for amino acids to maintain protein synthesis in vital tissues and organs and by providing hepatic gluconeogenic precursors. Although not a good indicator of body composition, the Quetelet index, also called body mass index (BMI), is often used for practical reasons. It is well known that high BMI predicts mortality and cardiovascular disease (CVD) in the general population. However, observational reports in the dialysis population have suggested that obesity is associated with improved survival, a phenomenon that is not well understood and subject to controversies. This review describes the characteristics of BMI in the general population and in chronic kidney disease (CKD) patients, as well as the respective role of muscle, whole body fat and fat distribution towards mortality, with particular emphasis on patients with CKD.

Metabolic effects of enteral versus parenteral alanyl-glutamine dipeptide administration in critically ill patients receiving enteral feeding: A pilot study

Glutamine (Gln) may become conditionally indispensable during critical illness. The short-term metabolic effects of enteral versus parenteral Gln supplementation are unknown in this clinical setting. We studied metabolic effects of intravenous (i.v.) alanyl-Gln dipeptide (AG) supplementation and enteral (e.n.) AG supplementation on plasma Gln concentration, antioxidant status, plasma lymphocyte subset number, gut permeability and nitrogen balance in adult critically ill patients requiring tube feeding compared to a control group not receiving Gln supplementation. In a double-blind, pilot clinical trial, 44 medical and surgical ICU patients received identical Gln-free tube feedings 24 h/day and were randomized to either isonitrogenous control (n=15), e.n. AG (n=15) or i.v. AG (n=14) groups (AG). Twelve patients were discontinued from the study. The goal AG dose was 0.5 g/kg/day. Biochemical and metabolic endpoints were measured at baseline and on day 9 (plasma Gln, antioxidant indices, lymphocyte subsets; serum IGF-1 and IGF-binding protein-3; intestinal permeability). Nitrogen balance was determined between study days 6 and 8. Illness severity indices, clinical demographics, enteral energy and nitrogen intake and major biochemical indices were similar between groups during study. Plasma Gln was higher in the i.v. AG (565+/-119 microM, mean+/-SEM) vs the e.n. AG (411+/-27 microM) group by day 9 (p=0.039); however, subjects in the i.v. AG group received a higher dose of AG (i.v. AG 0.50 versus e.n. AG 0.32+/-0.02 g/kg/day; p<0.001). E.n. AG subjects showed a significant increase in plasma alpha-tocopherol levels over time and maintained plasma gamma-tocopherol concentrations. There were no differences between groups for plasma concentrations of vitamin C, glutathione, malondialdehyde (MDA), T-lymphocyte subsets, intestinal permeability or nitrogen balance. This study showed that alanyl-Gln administration by enteral or parenteral routes did not appear to affect antioxidant capacity or oxidative stress markers, T-lymphocyte subset (CD-3, CD-4, CD-8) number, gut barrier function or whole-body protein metabolism compared to unsupplemented ICU patients requiring enteral tube feeding. Enteral Gln appeared to maintain plasma tocopherol levels in this pilot metabolic study.

Whole-body protein metabolism and energy expenditure in sheep selected for divergent wool production when fed above or below maintenance

Rates of whole-body protein turnover and energy expenditure were measured in two groups of wethers differing in estimated breeding values (EBVs) for wool growth, but with similar EBVs for fibre diameter and liveweight (LW). The sheep were offered a pelleted diet at 1.2 times their metabolisable energy (ME) requirement for maintenance (1.2 M) followed by either 0.8 M or 1.8 M for 5 weeks. In the 5th week, whole-body protein metabolism was estimated by using intravenous injection of 15N-glycine (g N/day) and whole-body energy expenditure rate (EE) was predicted by the CO2 entry rate technique using intravenous injection of NaH13CO3. The higher N intake (8.7 v. 20.4 g N/day, P &lt; 0.001) was associated with a higher whole-body protein flux (22.1 v. 34.2 g N/day, P &lt; 0.001), and a higher whole-body protein synthesis rate (17.0 v. 25.5 g N/day, P &lt; 0.001) and protein degradation rate (15.9 v. 20.7 g N/day, P &lt; 0.001). Irrespective of feeding levels, sheep with high-fleece EBVs (F+) synthesised and degraded more body protein N (g N/day) than sheep with low-fleece EBVs (F–), and F+ sheep also retained more ingested protein N (P &lt; 0.05) in wool and body tissue than F– sheep, but the significant differences due to genotypes disappeared when whole-body protein flux, synthesis and degradation were expressed as g N/kg LW0.75.day (metabolic weight). Estimates of EE were lower when the sheep were offered 0.8 M than when offered 1.8 M (5.85 v. 7.68 MJ/day, P &lt; 0.001) and were higher in F+ than in F– sheep (6.95 v. 6.58 MJ/day; P &lt; 0.05), but F+ sheep had a significantly lower (P &lt; 0.05) EE (MJ/kg LW0.75.day) than F– sheep. F+ animals also retained more energy in wool and wool-free body tissue than F– animals (P &lt; 0.05). The present study indicates that genetic selection for wool growth has resulted in increased efficiency of dietary protein and energy use for wool production and body-tissue growth in these sheep. Furthermore, there is no ‘trade off’ between deposition of nutrients in the body and wool in sheep with high EBVs for wool growth.

Effect of zinc supplementation on protein metabolism in late–middle-aged men: The Zenith study

Objective Zinc (Zn) is an essential trace element that is a potent enhancer of protein metabolism due to its numerous roles in metabolic processes. Protein turnover decreases with age. We determined whether a Zn supplementation, which increases serum Zn concentration and Zn exchangeable pool mass, modifies whole-body protein turnover and albumin and fibrinogen synthesis rates in late–middle-aged men. Methods Three groups of 16 healthy subjects 55–70 y of age participated in a randomized, doubled-blinded, placebo-controlled intervention. Each group received 0, 15, or 30 mg/d of supplemental Zn for 6 mo. At the end of the supplementation period, each subject received an intravenous infusion of L-[1- 13C] leucine to quantify whole-body leucine fluxes and synthesis rates of albumin and fibrinogen. Results In the placebo group, mean ± SEM whole-body leucine fluxes to protein synthesis, to oxidation, and from protein degradation were 1.46 ± 0.05, 0.40 ± 0.01, and 1.73 ± 0.06 μmol · kg −1 · min −1, respectively. Zn supplementation did not significantly change whole-body leucine fluxes. In the placebo group, plasma concentration and fractional rate of protein synthesis were 45 ± 1 g/L and 8.2 ± 0.6%/d for albumin and 3.6 ± 0.2 g/L and 16.7 ± 1.3%/d for fibrinogen, respectively. Zn supplementation did not significantly change these parameters or the absolute rates of synthesis of these proteins. Conclusion Increasing Zn supply does not modify whole-body protein metabolism and synthesis rates of albumin and fibrinogen in late–middle-aged men.

Insulin action on glucose and protein metabolism during L-carnitine supplementation in maintenance haemodialysis patients

Impaired protein anabolism and insulin resistance are characteristic features of maintenance haemodialysis patients. We have used a randomised, matched-paired, double-blind, placebo-controlled experimental design to determine the capability of intravenous L-carnitine supplementation to modify insulin resistance and protein catabolism in non-diabetic patients with end-stage renal disease (ESRD) undergoing chronic haemodialysis treatment. L-carnitine (20 mg x kg(-1)) (n = 9) or placebo (n = 10) were given intravenously at the end of seven consecutive dialysis sessions. Whole-body protein and glucose metabolism were assessed on interdialytic days by the L[1-(13)C]leucine and the [2,2-(2)H(2)]glucose kinetic models in the postabsorptive state and during euglicemic hyperinsulinemic clamp studies at baseline and at the end of the treatment period. L-carnitine supplementation was associated with lower (P < 0.05) rates of leucine oxidation (-11 +/- 12%) and appearance from proteolysis (-6 +/- 2%) during the clamp studies than after placebo supplementation. The rates of glucose appearance in the postabsorptive state did not change significantly in the patients receiving L-carnitine treatment. Insulin-mediated glucose disappearance was improved by L-carnitine only in those patients (n = 5) (+18 +/- 3%, P < 0.05 vs placebo group, n = 5) with greater baseline insulin resistance, selected according to the median value of insulin sensitivity before treatment. L-carnitine supplementation was associated with protein-sparing effects in maintenance haemodialysis patients during hyperinsulinemia.

Determinants of Whole-Body Protein Metabolism in Subjects With and Without Type 2 Diabetes

Whole-body protein metabolism is abnormal in suboptimally controlled type 2 diabetes and obesity. We hypothesized that glycemia, insulin resistance, and waist circumference modulate these alterations in type 2 diabetes and, to a lesser extent, in individuals without type 2 diabetes. In 88 lean and obese subjects without and 40 with type 2 diabetes on an inpatient protein-controlled isoenergetic diet for 7 days, whole-body protein turnover was measured using the fed-fasted 60-h oral (15)N-glycine method. Nitrogen flux was determined from urinary (15)N urea and protein synthesis, breakdown and net balance calculated. Indexes of diabetes control, resting energy expenditure (REE), and body composition were assessed. Higher protein turnover in obese subjects was further increased, and net balance was lower in type 2 diabetes. Waist-to-hip ratio and ln homeostasis model assessment of insulin resistance (HOMA-IR) explained 40% of the variance in flux in type 2 diabetes; fat-free mass and lnHOMA-IR explained 62% in subjects without type 2 diabetes. Overall, fasting glucose explained 16% of the variance in net balance. In type 2 diabetes, net balance correlated negatively with fasting glucose in men and positively with hip circumference in women. Kinetics of whole-body protein metabolism are elevated, and net balance is diminished in type 2 diabetes, independently of obesity. Elevated flux is associated with greater visceral adiposity, REE, and insulin resistance of glucose. In type 2 diabetic men, these alterations worsened with magnitude of hyperglycemia. In type 2 diabetic women, larger hip circumferences may protect against such alterations. Our findings suggest that dietary protein requirements may be greater in type 2 diabetes to offset a reduced net balance, aggravated as glycemia increases, especially in men.

Impact of Acute and Chronic Low-Dose Glucocorticoids on Protein Metabolism

High-dose glucocorticoids cause acute protein loss by increasing protein breakdown and oxidation. Whether lower glucocorticoid doses, typical of therapeutic use, induce sustained catabolism has not been studied. Our objective was to assess the effect of acute and chronic therapeutic glucocorticoid doses on protein metabolism. We conducted an open longitudinal and a cross-sectional study at a clinical research facility. Ten healthy subjects were studied before and after a short course of prednisolone (5 and 10 mg/d sequentially for 7 d each). Twelve subjects with inactive polymyalgia rheumatica receiving chronic (>12 months) prednisone (mean = 5.0 +/- 0.8 mg/d) were compared with 12 age- and gender-matched normal subjects. Whole-body protein metabolism was assessed using a 3-h primed constant infusion of 1-[(13)C]leucine, from which rates of leucine appearance (leucine Ra, an index of protein breakdown), leucine oxidation (Lox, index of protein oxidation) and leucine incorporation into protein (LIP, index of protein synthesis) were estimated. Prednisolone induced an acute significant increase in Lox (P = 0.008) and a fall in LIP (P = 0.08) but did not affect leucine Ra. There was no significant difference between the effects of the 5- and 10-mg prednisolone doses on leucine metabolism. In subjects receiving chronic prednisone therapy, leucine Ra, Lox, and LIP were not significantly different from normal subjects. Glucocorticoids stimulate protein oxidation after acute but not chronic administration. This time-related change suggests that glucocorticoid-induced stimulation of protein oxidation does not persist but that a metabolic adaptation occurs to limit protein loss.

Effects of the Method of Conservation of Timothy on Nitrogen Metabolism in Lactating Dairy Cows

Six ruminally and duodenally cannulated lactating primiparous Holstein cows were used to study the effects of different methods of conservation of timothy on N metabolism. Cows were assigned randomly to 2 replicated 3×3 Latin squares (35-d periods). Because of missing data from 2 cows, data were analyzed as a 3×4 Youden square. Diets contained a similar concentrate (44% of total ration on a dry matter basis) plus first-cut timothy conserved as hay, or as restrictively (formic) or extensively fermented silage (inoc). Crude protein contents were 10.4, 13.6, and 14.8% for hay, formic, and inoc, respectively. Hay and formic had a high soluble carbohydrate content (≥8.0% of dry matter) and formic and inoc had a high soluble protein content (≥8.0% of dry matter). Haying and restricting fermentation resulted in increased efficiency of partition to milk N (30.9, 28.2, 24.7% of N intake for hay, formic, and inoc, respectively). Despite a 14% lower N intake with hay, no effects of treatments were detected on microbial protein synthesis and apparent intestinal digestion of essential AA. Haying reduced feed protein degradation in the rumen, whereas this effect was not observed when restricting fermentation in the silage. Haying and restricting fermentation induced a lipogenic fermentation pattern in the rumen (4.55, 4.23, and 3.78 ratio of acetate to propionate for hay, formic, and inoc), but no effects on milk fat yield and plasma glucose were observed. Whole-body protein metabolism was unaffected by treatments.

Protein metabolism in adult patients with phenylketonuria

Objective Protein intake recommendations in phenylketonuria (PKU) are frequently the subject of discussion. For healthy adults, the recommended daily allowance (RDA) is 0.8 g · kg −1 · d −1, which is generally lower than that observed in the general Western population. We investigated whether whole-body protein metabolism in patients with PKU is comparable to that of healthy controls at a RDA rate of protein intake. Methods Six adult patients with well-controlled PKU and six healthy subjects of comparable age, height, and weight were studied using a primed continuous infusion of [1- 13C]-valine for 8 h after an overnight fast before and during frequent meals. Normal protein was given to controls, whereas patients with PKU received a combination of an amino acid mixture and natural protein. Results No significant differences were observed between patients with PKU and controls in preprandial and prandial rates of valine appearance and oxidation and protein breakdown, protein synthesis, and net protein balance. Feeding resulted in a significant ( P < 0.01) decrease in protein breakdown (PKU: 94 ± 15 μmol · kg −1 · h −1 preprandial to 49 ± 10 μmol · kg −1 · h −1 prandial; controls: 97 ± 10 μmol · kg −1 · h −1 preprandial to 55 ± 10 μmol · kg −1 · h −1 prandial), whereas no effects were observed in protein synthesis (PKU: 77 ± 10 μmol · kg −1 · h −1 preprandial to 73 ± 7 μmol · kg −1 · h −1 prandial; controls: 76 ± 8 μmol · kg −1 · h −1 preprandial to 71 ± 5 μmol · kg −1 · h −1 prandial). Net protein balance increased from negative prandial to positive preprandial values (PKU: −17 ± 6 μmol · kg −1 · h −1 preprandial to +23 ± 8 μmol · kg −1 · h −1 prandial; controls: −21 ± 4 μmol · kg −1 · h −1 preprandial to +16 ± 9 μmol · kg −1 · h −1 prandial). Conclusion Whole-body protein metabolism in adult patients with PKU is fully comparable to that in healthy controls at the RDA level of protein intake.

Postprandial whole-body protein metabolism after a meat meal is influenced by chewing efficiency in elderly subjects

Background: The rate of protein digestion affects protein utilization in elderly subjects. Although meat is a widely consumed protein source, little is known of its digestion rate and how it can be affected by the chewing capacity of elderly subjects.Objectives: We used a [1-13C]leucine balance with a single-meal protocol to assess the absorption rate of meat protein and to estimate the utilization of meat protein in elderly subjects with different chewing efficiency.Design: Twenty elderly volunteers aged 60–75 y were involved in the study. Ten of them had healthy natural dentition, and the other 10 were edentulous and wore complete dentures. Whole-body fluxes of leucine, before and after the meal (120 g beef meat), were measured with the use of a [1-13C]leucine intravenous infusion.Results: A rapid increase in plasma aminoacidemia and plasma leucine entry rate was observed after meat intake in dentate subjects. In complete denture wearers the increase in leucine entry rate was delayed (P < 0.05), and the amount of leucine appearing in peripheral blood during the whole postprandial period was lower than in dentate subjects (P < 0.01). Postprandial whole-body protein synthesis was lower in denture wearers than in dentate subjects (30% compared with 48% of leucine intake, respectively; P < 0.05).Conclusion: Meat proteins could be classified as fast digested proteins. However, this property depends on the chewing capacity of elderly subjects. This study showed that meat protein utilization for protein synthesis can be impaired by a decrease in the chewing efficiency of elderly subjects.

Lack of Effect of Acute Enteral Arginine Infusion on Whole-Body and Intestinal Protein Metabolism in Humans

Arginine is a conditionally essential amino acid and exerts anabolic effects. We studied the effects of enteral arginine on whole-body and duodenal protein metabolism. Eight healthy fasted volunteers received randomly a 5-hr enteral infusion of either arginine (Arg; 20 g) or an isonitrogenous amino acid mixture (AA) and an IV infusion of [13C]leucine. Duodenal biopsies were performed. Whole-body protein turnover and duodenal protein synthesis (FSR) were calculated from GC/MS-assessed enrichment. The mRNA levels for major components of proteolytic pathways, ubiquitin, cathepsin D, and m-calpain, were evaluated by RT-PCR. Results were compared using paired Wilcoxon test. Endogenous, oxidative, and nonoxidative leucine fluxes were not different after Arg and AA infusions, respectively. Duodenal mucosal protein FSR (71% +/- 26% vs 81% +/- 30%/day) and mRNA levels of ubiquitin, cathepsin D, and m-calpain were also similar after Arg and AA infusions. We conclude that in healthy subjects, arginine infusion exerts no effect on whole-body and duodenal protein metabolism. Whether arginine might specifically affect these parameters in catabolic or inflammatory situations remains to be determined.

The underappreciated role of muscle in health and disease

Muscle plays a central role in whole-body protein metabolism by serving as the principal reservoir for amino acids to maintain protein synthesis in vital tissues and organs in the absence of amino acid absorption from the gut and by providing hepatic gluconeogenic precursors. Furthermore, altered muscle metabolism plays a key role in the genesis, and therefore the prevention, of many common pathologic conditions and chronic diseases. Nonetheless, the maintenance of adequate muscle mass, strength, and metabolic function has rarely, if ever, been targeted as a relevant endpoint of recommendations for dietary intake. It is therefore imperative that factors directly related to muscle mass, strength, and metabolic function be included in future studies designed to demonstrate optimal lifestyle behaviors throughout the life span, including physical activity and diet.

Whole-Body Proteolysis Rate Is Elevated in HIV-Associated Insulin Resistance

Type 2 diabetes is characterized by impaired glucose tolerance (IGT) and insulin resistance with respect to glucose metabolism but not amino acid metabolism. We examined whether whole-body leucine and protein metabolism are dysregulated in HIV-infected individuals with IGT. Glucose and leucine kinetics were measured under fasting insulin conditions and during euglycemic hyperinsulinemia using primed-constant infusions of 2H2-glucose and 13C-leucine in 10 HIV-seronegative control subjects, 16 HIV+ subjects with normal glucose tolerance, and 21 HIV+IGT subjects. Glucose disposal rate during hyperinsulinemia was lower in HIV+IGT than the other two groups. Absolute plasma leucine levels and rate of appearance (whole-body proteolysis) were higher in HIV+IGT at all insulin levels but declined in response to hyperinsulinemia in parallel to those in the other two groups. HIV+IGT had greater visceral adiposity, fasting serum interleukin (IL)-8 and free fatty acid levels, and higher lipid oxidation rates during the clamp than the other two groups. These findings implicate several factors in the insulin signaling pathway, which may be further dysregulated in HIV+IGT, and support the notion that insulin signaling pathways for glucose and leucine metabolism may be disrupted by increased proinflammatory adipocytokines (IL-8) and increased lipid oxidation. Increased proteolysis may provide amino acids for gluconeogenesis, exacerbating hyperglycemia in HIV.

Whole‐Body Protein Metabolism in Chronic Heart Failure: Relationship to Anabolic and Catabolic Hormones

Patients with chronic heart failure frequently experience profound wasting during the course of the disease, a condition termed cardiac cachexia. Although protein is the primary structural and functional component of most tissues, few studies have examined the effect of heart failure on protein metabolism. Moreover, no study has assessed the relationship of protein turnover to hormonal alterations thought to promote cachexia. Thus, our goal was to determine if whole-body protein metabolism is altered in heart failure patients and to assess the relationship of protein kinetics to circulating levels of anabolic and catabolic hormones. We measured whole-body protein metabolism using 13C-leucine, body composition, and circulating anabolic and catabolic hormone levels in 10 patients with chronic heart failure and 11 elderly controls. No differences in leucine rate of appearance, oxidation, or nonoxidative disposal were noted between heart failure patients and controls. However, in a subgroup of patients characterized by increased resting energy expenditure for their metabolic body size (n = 4; > or = 20% above that predicted from fat-free mass), leucine rate of appearance (mean +/- SE; 146 +/- 6 micromol/min), an index of protein breakdown, tended to be higher compared with patients with normal resting energy expenditure (n = 5; 120 +/- 8 micromol/min) and controls (127 +/- 4 micromol/min; p = .06). Alterations in anabolic/catabolic hormone balance did not explain increased protein breakdown in this subgroup, and no correlations were found between hormone levels and protein breakdown in the heart failure group as a whole. In contrast, increased circulating interleukin-6 soluble receptor (r = 0.829; p < .01) and reduced insulin-like growth factor-I (r =-.751; p < .05) levels were related to greater rates of leucine oxidation in heart failure patients. Our results demonstrate that, although increased protein turnover is not a generalized feature of heart failure, there is a subgroup of patients characterized by resting hypermetabolism and increased protein breakdown. Moreover, hormonal alterations related to the heart failure syndrome were related to increased protein oxidation.

Fat and protein metabolism in growing steers fed either grass silage or dried grass

Cattle fed grass silage diets have been reported to have high carcass fat:protein ratios. The effect of grass silage and dried grass diets, fed at different levels of intake to ensure a range of equivalent metabolisable energy intakes (MEI) from 1 .1 x metabolisable energy requirement for maintenance to ad libitum, on fat and protein metabolism in twenty-four Hereford x Friesian steers was investigated. After about 84 d of dietary treatment rates of whole-body fat and protein metabolism were measured, as were rates of lipogenesis in omental, perirenal and subcutaneous adipose tissue. Carcass composition was determined. Animals fed silage had greater (P<0 .001) carcass fat:protein ratios than animals fed dried grass at equivalent levels of MEI. Animals fed silage had lower (P<0 .001) rates of protein gain. Rates of leucine entry and oxidation were lower (P<0 .001) in animals fed silage, but there was no dietary difference in the rate of whole-body protein synthesis. There was no dietary difference in the rate of carcass fat gain, but rates of lipogenesis in perirenal adipose tissue were significantly (P=0 .007) higher in animals fed silage. There was no dietary difference in the rate of palmitate and glycerol entry or palmitate oxidation. There were no interactions between MEI and diet, indicating that increments of energy were utilised with the same efficiency from both diets. It was concluded that the high carcass fat:protein ratios of young growing steers was due to limited rates of protein accretion and not to elevated rates of carcass fat accretion.

The Regulation of Body and Skeletal Muscle Protein Metabolism by Hormones and Amino Acids1–3

For many decades, it has been recognized that insulin, growth hormone, glucocorticoids, insulin-like growth factor 1, thyroid hormones, and other hormones regulate body protein metabolism. It has been more recently recognized, but not understood, that humor factors present in states of acute and chronic inflammation could have a strong impact on protein turnover. Most recently, the role of amino acids, acting as signaling molecules, has become increasingly clarified. In aggregate, these factors (together with neuromuscular activity) determine the balance of body protein mass. We will review some of these data, particularly focusing on amino acids, insulin, and the growth hormone axis and their actions in muscle and how these relate to whole-body protein metabolism.

Oxidative Metabolism Appears to Be Reduced in Long-Term Hemodialysis Patients

As part of a study of whole-body protein metabolism in hemodialysis (HD) patients, we obtained values for whole-body bicarbonate production in control subjects and HD patients before and during dialysis by using stable isotopically labeled bicarbonate. Indirect calorimetry measurements have shown normal or increased energy expenditure in HD patients, which has been used to explain the malnutrition in many of these patients. However, this method becomes inaccurate when the dynamics of whole-body bicarbonate production change during measurement, as is the case with HD patients during dialysis. Whole-body bicarbonate production was measured in 6 control subjects, 9 patients on a nondialysis day (HD-), and 8 patients during an HD session (HD+) by means of a primed constant infusion of carbon 13 (13C)-labeled sodium carbonate (NaH13CO3). 13C-abundance of expired carbon dioxide was measured by means of isotope ratio mass spectrometry. Carbon dioxide production was 141 +/- 12, 123 +/- 11*, and 148 +/- 19 micromol/kg/min for the control, HD-, and HD+ groups, respectively (*P < 0.05 compared with the control and HD+ groups). Values for energy expenditure were derived and were 29.1 +/- 2.4, 24.9 +/- 2.1*, and 32.6 +/- 2.0 kcal/kg/day, respectively (*P < 0.05 compared with the control and HD+ groups). Whole-body oxidation in HD patients is reduced compared with control subjects. During dialysis, bicarbonate turnover, as well as carbon dioxide expiration, increases because of the influx of bicarbonate from the dialyzer.