scholarly journals What is the proper precursor-to-product labeling relationship for calculating the fractional synthetic rate of muscle triglyceride?: Fig. 1.

2011 ◽  
Vol 53 (1) ◽  
pp. 1-3 ◽  
Author(s):  
Henri Brunengraber
2001 ◽  
Vol 91 (3) ◽  
pp. 1041-1047 ◽  
Author(s):  
G. Parise ◽  
S. Mihic ◽  
D. MacLennan ◽  
K. E. Yarasheski ◽  
M. A. Tarnopolsky

Creatine monohydrate (CrM) supplementation during resistance exercise training results in a greater increase in strength and fat-free mass than placebo. Whether this is solely due to an increase in intracellular water or whether there may be alterations in protein turnover is not clear at this point. We examined the effects of CrM supplementation on indexes of protein metabolism in young healthy men ( n = 13) and women ( n = 14). Subjects were randomly allocated to CrM (20 g/day for 5 days followed by 5 g/day for 3–4 days) or placebo (glucose polymers) and tested before and after the supplementation period under rigorous dietary and exercise controls. Muscle phosphocreatine, creatine, and total creatine were measured before and after supplementation. A primed-continuous intravenous infusion of l-[1-13C]leucine and mass spectrometry were used to measure mixed-muscle protein fractional synthetic rate and indexes of whole body leucine metabolism (nonoxidative leucine disposal), leucine oxidation, and plasma leucine rate of appearance. CrM supplementation increased muscle total creatine (+13.1%, P < 0.05) with a trend toward an increase in phosphocreatine (+8.8%, P = 0.09). CrM supplementation did not increase muscle fractional synthetic rate but reduced leucine oxidation (−19.6%) and plasma leucine rate of appearance (−7.5%, P < 0.05) in men, but not in women. CrM did not increase total body mass or fat-free mass. We conclude that short-term CrM supplementation may have anticatabolic actions in some proteins (in men), but CrM does not increase whole body or mixed-muscle protein synthesis.


2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
Tiffany A Thomas ◽  
Haihong Zhou ◽  
Thomas Roddy ◽  
Stephen Previs ◽  
Michael Lassman ◽  
...  

Objective: Anacetrapib, a CETP inhibitor, was previously shown to decrease plasma lipoprotein (a) [Lp(a)] levels by 35-40% in subjects also taking a statin. Thus, anacetrapib is an efficacious Lp(a)-lowering agent. The goal of this study was to define the mechanism by which anacetrapib lowers plasma Lp(a) levels. Methods: 39 moderately hyperlipidemic volunteers were enrolled in a fixed-sequence study, in which 75% were on atorvastatin 20mg/day, plus placebo for four weeks (period 1), and then atorvastatin plus anacetrapib (100 mg/day) for 8 weeks (period 2). The other 25% of the subjects received double placebo for four weeks, and then placebo plus anacetrapib for 8 weeks. Turnover studies using D3-leucine were performed at the end of each period. The present analysis utilized samples from a subset of subjects (n=12) who had plasma Lp(a) levels greater than 10 nM at the end of period 1 and had a greater than 10% reduction in Lp(a) by the end of period 2. The fractional synthetic rate (FSR:equal to fractional catabolic rate at steady state) of mature Lp(a), isolated from a D:1.019-1.21 g/ml density interval, was determined from the enrichment of a leucine-containing peptide specific to apo(a). The production rate (PR) of mature Lp(a) was calculated from the FSR and the Lp(a) pool size. To date, we have calculated the FSR and PR in 4 participants. Results: Baseline Lp(a) mean levels were 45.7 ± 6.3nM in the entire group and 56.5 ± 33.6nM in the 12 qualifying subjects. Anacetrapib lowered Lp(a) by 43 ± 22% in the 12 subjects and 21 ±12% in the 4 subjects with turnover data. In these 4 subjects, the reduction in mature Lp(a) was associated with a 24% reduction in FSR and a 41% reduction in PR. Lp(a) kinetics analyses of the remaining 8 subjects are in progress. Conclusion: These preliminary results suggest that anacetrapib decreases Lp(a) levels by significantly decreasing the production of mature Lp(a). Additional analyses are planned to determine if the reduced production of Lp(a) results from decreased entry of Lp(a) into plasma or reduced conversion of a precursor form to the mature Lp(a).


1990 ◽  
Vol 259 (4) ◽  
pp. E470-E476 ◽  
Author(s):  
F. Carraro ◽  
C. A. Stuart ◽  
W. H. Hartl ◽  
J. Rosenblatt ◽  
R. R. Wolfe

Previous studies using indirect means to assess the response of protein metabolism to exercise have led to conflicting conclusions. Therefore, in this study we have measured the rate of muscle protein synthesis in normal volunteers at rest, at the end of 4 h of aerobic exercise (40% maximal O2 consumption), and after 4 h of recovery by determining directly the rate of incorporation of 1,2-[13C]leucine into muscle. The rate of muscle protein breakdown was assessed by 3-methylhistidine (3-MH) excretion, and total urinary nitrogen excretion was also measured. There was an insignificant increase in 3-MH excretion in exercise of 37% and a significant increase (P less than 0.05) of 85% during 4 h of recovery from exercise (0.079 +/- 0.008 vs. 0.147 +/- 0.0338 mumol.kg-1.min-1 for rest and recovery from exercise, respectively). Nonetheless, there was no effect of exercise on total nitrogen excretion. Muscle fractional synthetic rate was not different in the exercise vs. the control group at the end of exercise (0.0417 +/- 0.004 vs. 0.0477 +/- 0.010%/h for exercise vs. control), but there was a significant increase in fractional synthetic rate in the exercise group during the recovery period (0.0821 +/- 0.006 vs. 0.0654 +/- 0.012%/h for exercise vs. control, P less than 0.05). Thus we conclude that although aerobic exercise may stimulate muscle protein breakdown, this does not result in a significant depletion of muscle mass because muscle protein synthesis is stimulated in recovery.


1990 ◽  
Vol 259 (6) ◽  
pp. E763-E769 ◽  
Author(s):  
M. Wusteman ◽  
D. G. Wight ◽  
M. Elia

Subcutaneous injections of turpentine induced discrete aseptic abscesses in rats without detectable injury to other tissues. Hypoalbuminemia and high circulating concentrations of alpha 2-macroglobulin were present after 48 h. Liver size, protein content, and protein fractional synthetic rate (FSR) were all increased, whereas loss of muscle protein occurred together with similar (45-50%) reductions in both intramuscular glutamine concentrations ([Gln]i, mmol/l intracellular water) and FSR. The rats became anorexic, but pair feeding (50% ad libitum for 48 h) produced a 22% increase in muscle [Gln]i and only an 18% reduction in muscle FSR. Dietary restriction therefore did not demonstrate the positive relationship between muscle [Gln]i and FSR, which has been observed in animal trauma studies. It is concluded that subcutaneous injections of turpentine produce many of the features of the acute-phase response to injury, and therefore this technique is recommended as a convenient laboratory model for studying various aspects of the protein metabolic response to injury.


1993 ◽  
Vol 34 (12) ◽  
pp. 2193-2205 ◽  
Author(s):  
DM Foster ◽  
PH Barrett ◽  
G Toffolo ◽  
WF Beltz ◽  
C Cobelli

Author(s):  
Seongkyun Lim ◽  
J. William Deaver ◽  
Megan E. Rosa-Caldwell ◽  
Wesley S. Haynie ◽  
Francielly Morena Da Silva ◽  
...  

Cancer cachexia (CC) results in impaired muscle function and quality of life and is the primary cause of death for ~20-30% of cancer patients. We demonstrated mitochondrial degeneration as a precursor to CC in male mice, however, if such alterations occur in females is currently unknown. The purpose of this study was to elucidate muscle alterations in CC development in female tumor-bearing mice. 60 female C57BL/6J mice were injected with PBS or Lewis Lung Carcinoma at 8-week age, and tumors developed for 1, 2, 3, or 4 weeks to assess the time course of cachectic development. In vivo muscle contractile function, protein fractional synthetic rate (FSR), protein turnover, and mitochondrial health were assessed. 3- and 4-week tumor-bearing mice displayed a dichotomy in tumor growth and were reassigned to High Tumor (HT) and Low Tumor (LT) groups. HT mice exhibited lower soleus, TA, and fat weights compared to PBS. HT mice showed lower peak isometric torque and slower one-half relaxation time compared to PBS. HT mice had lower FSR compared to PBS while E3 ubiquitin ligases were greater in HT compared to other groups. Bnip3 (mitophagy) and pMitoTimer red puncta (mitochondrial degeneration) were greater in HT while Pgc1α1 and Tfam (mitochondrial biogenesis) were lower in HT compared to PBS. We demonstrate alterations in female tumor-bearing mice where HT exhibited greater protein degradation, impaired muscle contractility, and mitochondrial degeneration compared to other groups. Our data provide novel evidence for a distinct cachectic development in tumor-bearing female mice compared to previous male studies.


1993 ◽  
Vol 264 (1) ◽  
pp. E128-E135 ◽  
Author(s):  
G. Toffolo ◽  
D. M. Foster ◽  
C. Cobelli

The fractional synthetic rate (FSR) is a key parameter characterizing protein turnover that is estimated from tracer kinetic data. Formulas to estimate this parameter usually assume a precursor-product model. Assuming this model is correct, we discuss these formulas to estimate the FSR in the steady and non-steady state both for the radioactive and stable isotope tracer. Then we deal with the non-steady-state case where the FSR becomes time varying and derive formulas for its estimation. A non-steady-state case study on the flooding-dose technique for measuring protein turnover is presented.


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