This study tests the hypotheses that (a) a mixture of whey protein, amino acids (AA), and carbohydrates (CHO) stimulates net muscle protein synthesis to a greater extent than isoenergetic CHO alone after resistance exercise; and (b) that the stimulatory effect of a protein, AA, and CHO mixture will last beyond the 1st hour after intake. Eight subjects participated in 2 trials. In one (PAAC), they ingested 77.4 g CHO, 17.5 g whey protein, and 4.9 g AA 1 hr after resistance exercise. In the other (CON), 100 g CHO was ingested instead. They received a primed constant infusion of L-[2H5]-phenylalanine, and samples from femoral artery and vein, and biopsies from vastus lateralis were obtained. The area under the curve for net uptake of phenylalanine into muscle above pre-drink value was 128+/- 42 mg x leg(- 1) (PAAC) versus 32+/- 10 mg x leg (-1) (CON) for the 3 hr after the drink (p =.04). The net protein balance response to the mixture consisted of two components, one rapid immediate response, and a smaller delayed response about 90 min after drink, whereas in CON only a small delayed response was seen. We conclude that after resistance exercise, a mixture of whey protein, AA, and CHO stimulated muscle protein synthesis to a greater extent than isoenergetic CHO alone. Further, compared to previously reported findings, the addition of protein to an AA+ CHO mixture seems to extend the anabolic effect.
Trauma and critical illness are associated with a stress response that results in increased skeletal muscle protein catabolism, which is thought to facilitate the synthesis of acute phase proteins in the liver as well as proteins involved in immune function. What makes burn injury a unique form of trauma is the existence of vast skin lesions, where the majority of afflicted tissue is often surgically excised post injury. Thereafter, recovery is dependent on the formation of a significant quantity of new skin, meaning that the burned patient requires a large and sustained supply of amino acids to facilitate wound healing. Skeletal muscle has the capacity to store surplus glucose and fatty acids within glycogen and triacylglycerol depots respectively, where glycogen and fatty acids can be mobilized during prolonged periods of caloric restriction or heightened metabolic demand (e.g., exercise), to be catabolized in order to maintain cellular ATP availability. Amino acids, on the other hand, are not generally considered to be stored in such a manner within skeletal muscle, i.e., in a temporary pool independent of structural proteins and cellular organelles etc. Subsequently, in response to severe thermal trauma, skeletal muscle assumes the role of an amino acid reserve where muscle protein breakdown and amino acid release from skeletal muscle serves to buffer plasma amino acid concentrations. Interestingly, it seems like aggressive feeding of the severely burned patient may not necessarily supply amino acids in sufficient abundance to normalize skeletal muscle protein metabolism, suggest - ing that skeletal muscle becomes an essential store of protein in patients suffering from severe burn trauma. In this article, the effects of burn injury on whole body and skeletal muscle protein metabolism will be discussed in an attempt to distill the current understanding of the impact of this debilitating injury on the redistribution of skeletal muscle protein stores.
Abstract Objectives Platelets (PL) are an accessible source of human mitochondria. Thus, PL are advantageous when studying mitochondrial function in vulnerable populations. The objective of this study was to measure the association between parameters of PL mitochondrial respiration and markers of cardiovascular disease risk [adiposity, fitness and blood pressure (BP)] in a sub-sample of school age children participants of a larger study called Arkansas Active Kids. Methods After overnight fasting, body composition (DXA), VO2peak (incremental cycle ergometer test), resting BP, and mitochondrial function of permeabilized platelets (high-resolution respirometry) were measured in 46 children. Routine respiration (R), fatty acid oxidation (F = octanoylcarnitine + ADP + malate), respiratory stimulation by simultaneous action of F plus NADH-linked complex (C) I substrates (F&CI = pyruvate, malate and glutamate), succinate (F&CI&CII), and glycerolphosphate (F&CI&CII&GpDH) were measured. Noncoupled electron transfer capacity (ETE, FCCP), CIIE&GpDHE respiration (rotenone), residual oxygen consumption (ROX, antimycin) and CIV activity were also measured. Flux control ratios were computed by normalizing to ET capacity in the presence of NADH-linked substrates. Data presented as mean ± SD and Spearman correlations (Rho). Results Children were 9 ± 1 years with an average BMI percentile (BMIp) of 59 ± 30, and % fat mass (%FM) of 33 ± 6% (range: 25 to 49%). Ten children (22%) had either elevated or stage 1 hypertension as defined by the American Academy of Pediatrics. Diastolic BP percentile, VO2peak (ml·kg−1 fat-free-mass−1), BMIP, and % fat mass (%FM) did not correlate with any parameter of platelet mitochondrial respiration. However, visceral fat area (cm2) correlated with FAO (Rho = 0.35, P = 0.017) and F&CI (Rho = 0.30, P = 0.043) while systolic BP correlated with F&CI&CII&GpDH (Rho = 0.31, P = 0.037) and ETE (Rho = 0.43, P = 0.003). Conclusions In this preliminary analysis, PL fatty acid oxidation of school-age children increased with increasing visceral adiposity while the convergent electron flow through the Q-junction increased with increasing systolic blood pressure. Funding Sources USDA 59-6250-4-001; NIH P20GM109096. USDA/ARS Project 6026-51000-010-05S.
Background The composition of postnatal diet (i.e., breastmilk vs. formula) has a strong influence on a variety of physiological outcomes in infants, but the impact on bioenergetics and mitochondrial function remains an open question. In a published study (1), early ingestion of dairy‐based infant formula vs. human breast milk differently modulated liver mitochondrial function and gut microbiota in rodents. However, the effects on bioenergetics in other tissues, including the gut, and the persistent effect after weaning remain unknown. In the current study we used a piglet model to determine the effects of these two milk types on bioenergetics phenotypes in the ileum. Methods Neonatal piglets were fed isocaloric diets of either human breast milk (n=9) or a dairy‐based infant formula (n=9) from 48 hours post‐delivery until day 21, followed by an ad libitum solid diet until day 51. Subsequently, ileum biopsies were collected for evaluation of permeabilized cell mitochondrial function by high resolution respirometry, following a substrate and inhibitor protocol. In addition, gene expression for a key regulator of mitogenesis and mitochondrial function, peroxisome proliferator‐activated receptor gamma coactivator 1‐alpha (PGC‐1α) was assessed. Results ATP‐linked respiration tended to be increased in the ileum of piglets fed a dairy‐based infant formula compared to those fed with human breast milk, even at 4 weeks of post‐weaning neonatal diet (10.4 +/− 2.2 vs. 5.8 +/− 0.9 pmol·s −1 ·mg −1 ; p=0.07). Cytochrome c oxidase (COX) activity was significantly elevated in the formula compared to the human breast milk (23.3 +/− 4.8 vs. 9.9 +/− 1.8 pmol·s −1 ·mg −1 ; p=0.02). Thus, the substrate control ratio for succinate relative to COX was significantly lower in the dairy fed group (0.07 +/− 0.02 vs. 0.14 +/− 0.02; p=0.03). Interestingly, PGC‐1α gene expression tended to be elevated (2.3 fold, p=0.06) in ileum of formula‐fed piglets compared to those fed human breast milk. Conclusion We conclude that different milk diets may have a sustained impact on ileum bioenergetics in neonatal piglets, even a month after discontinuation of the milk diets. Future efforts are needed to understand the implications of these novel findings on infant tissue function and whole‐body macronutrient metabolism. Support or Funding Information Funded by USDA ARS Project 6026 51000 010 05S. FEDER and FEDER funds through the Operational Programme Competitiveness Factors ‐ COMPETE and UID/NEU/04539/2013.
It has been recognized that mechanical stresses associated with physical activity (PA) have beneficial effects on increasing bone mineral density (BMD) and improving bone quality. On the other hand, high fat diet (HFD) and obesity increase bone marrow adiposity leading to increased excretion of pro‐inflammatory cytokines to activate RANKL‐induced bone resorption. In the current study, we investigated whether increased PA via access to voluntary wheel running protects against HFD‐induced bone resorption. One‐month‐old male C57BL6/J mice were provided ad libitum access to either control (17% fat) or HFD [20% protein (casein), 35% carbohydrate (dextrose and maltodextrin), and 45% fat (corn oil)] for 8 wk. Mice in each diet group were further divided into subgroups with or without PA by providing access to voluntary running wheels for 8 wk (8 to 9 km running per day). Using peripheral quantitative CT scan (pQCT) on tibias ex vivo , we found that bone mass especially trabecular BMD was significantly increased with PA in control diet animals compared to sedentary animals without access to wheels (102.8±3.5 vs. 91.5±4.2 mg/cm 3 , n=6, p<0.05). PA ameliorated HFD‐induced trabecular bone loss (PA+HFD, 93.6±5.2 vs. HFD, 81.3±4.7 mg/cm 3 , n=6, p<0.05). Femur bone marrow cells were aspirated and cultured, and non‐adherent hematopoietic cells collected the following day were used for RANKL‐induced osteoclastogenesis assay. We found that PA significantly blunted increases of HFD‐induced osteoclastogenesis. In accordance with these data, signal transduction real‐time PCR analysis showed that PA significantly inhibited HFD‐induced Ezh2 and NFATc1 gene expression, but IRF8 expression was decreased in non‐adherent hematopoietic cells from HFD mice. In conclusion, increased PA is capable of altering the HFD‐induced bone marrow hematopoietic cell differentiation program to protect against increased bone resorption. Supported in part by USDA‐ARS Project 6026‐51000‐010‐05S. Support or Funding Information USDA‐ARS Project 6026‐51000‐010‐05S
Background: Non‐alcoholic liver disease increases with age. There is scant information on gender differences in relation to its behavior, health consequences and treatment response. Aims: 1). To examine gender effect on changes (Δ) in liver fat, body fat, and high‐sensitivity C‐reactive protein (hs‐CRP), a marker of subclinical inflammation and increased cardiovascular risk, in response to supplemental essential amino acids (sEAA); 2) To correlate Δ in liver and body fat with hs‐CRP Δ. Methods: 12 subjects (7 women) with impaired glucose tolerance, age 67 years, ingested 22 g of sEAA daily for 8 weeks, after a placebo run‐in. Participants did not change diet or physical activity. Liver fat (nuclear magnetic spectroscopy; n=7), body fat (DEXA) and hs‐CRP levels (ELISA) were measured. Results: Liver fat (0.403 to 0.209,intrahepatic triglyceride/Intralipid standard) and hs‐CRP (2.28 to 1.55 mg/L), but not body fat, decreased at 8 weeks from baseline. Analysis of variance showed a gender effect (p=0.047) for Δ in liver fat and hs‐CRP. Liver fat Δ, but not body fat Δ, was associated with hs‐CRP Δ in women (Spearman coefficients 0.63, p=0.067 overall; 0.9, p=0.037 in women; p=0.2 in men). Conclusion: There may be significant gender differences on the effects of sEAA on hepatic steatosis and hs‐CRP levels. Grant Funding Source : AG033761 , D34HP18956, UL1TR000071‐05, AG024832
Obesity is increasing worldwide in prepubertal children, reducing the age of onset of associated comorbidities, including type 2 diabetes. Sulfur‐containing amino acids, methionine, cysteine, and their derivatives play important roles in the transmethylation and transsulfuration pathways. Dysregulation of these pathways leads to alterations in the cellular methylation patterns and an imbalanced redox state. Therefore, we tested the hypothesis that one‐carbon metabolism is already dysregulated in prepubertal children with obesity. Peripheral blood was collected from 64 children, and the plasma metabolites from transmethylation and transsulfuration pathways were quantified by HPLC. The cohort was stratified by BMI z‐scores and HOMA‐IR indices into healthy lean (HL), healthy obese (HO), and unhealthy obese (UHO). Fasting insulin levels were higher in the HO group compared to the HL, while the UHO had the highest. All groups presented normal fasting glycemia. Furthermore, high‐density lipoprotein (HDL) was lower while triglycerides and lactate levels were higher in the UHO compared to HO subjects. S‐adenosylhomocysteine (SAH) and total homocysteine levels were increased in the HO group compared to HL. Additionally, glutathione metabolism was also altered. Free cystine and oxidized glutathione (GSSG) were increased in the HO as compared to HL subjects. Importantly, the adipocyte secretory function was already compromised at this young age. Elevated circulating leptin and decreased adiponectin levels were observed in the UHO as compared to the HO subjects. Some of these alterations were concomitant with alterations in the DNA methylation patterns in the obese group, independent of the impaired insulin levels. In conclusion, our study informs on novel and important metabolic alterations in the transmethylation and the transsulfuration pathways in the early stages of obesity. Moreover, the altered secretory function of the adipocyte very early in life may be relevant in identifying early metabolic markers of disease that may inform on the increased risk for specific future comorbidities in this population.
Age-associated mitochondrial dysfunction and oxidative damage are primary causes for multiple health problems including sarcopenia and cardiovascular disease (CVD). Though the role of Nrf2, a transcription factor that regulates cytoprotective gene expression, in myopathy remains poorly defined, it has shown beneficial properties in both sarcopenia and CVD. Sulforaphane (SFN), a natural compound Nrf2-related activator of cytoprotective genes, provides protection in several disease states including CVD and is in various stages of clinical trials, from cancer prevention to reducing insulin resistance. This study aimed to determine whether SFN may prevent age-related loss of function in the heart and skeletal muscle. Cohorts of 2-month-old and 21- to 22-month-old mice were administered regular rodent diet or diet supplemented with SFN for 12 weeks. At the completion of the study, skeletal muscle and heart function, mitochondrial function, and Nrf2 activity were measured. Our studies revealed a significant drop in Nrf2 activity and mitochondrial functions, together with a loss of skeletal muscle and cardiac function in the old control mice compared to the younger age group. In the old mice, SFN restored Nrf2 activity, mitochondrial function, cardiac function, exercise capacity, glucose tolerance, and activation/differentiation of skeletal muscle satellite cells. Our results suggest that the age-associated decline in Nrf2 signaling activity and the associated mitochondrial dysfunction might be implicated in the development of age-related disease processes. Therefore, the restoration of Nrf2 activity and endogenous cytoprotective mechanisms by SFN may be a safe and effective strategy to protect against muscle and heart dysfunction due to aging.
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