Biomedical subjects

Mazen J Hamadeh

Publications and source records attributed to Mazen J Hamadeh.

10 recordsLinked to original sources

PubMed2006

Influence of endurance exercise training and sex on intramyocellular lipid and mitochondrial ultrastructure, substrate use, and mitochondrial enzyme activity.

Impaired mitochondrial function and structure and intramyocellular lipid (IMCL) accumulation have been associated with obesity and Type 2 diabetes. We examined whether endurance exercise training and sex influenced IMCL and mitochondrial morphology using electron microscopy, whole-body substrate use, and mitochondrial enzyme activity. Untrained men (n = 5) and women (n = 7) were tested before and after 7 wk of endurance exercise training. Testing included 90 min of cycle ergometry at 60% Vo(2 peak) with preexercise muscle biopsies analyzed for IMCL and mitochondrial size/area using electron microscopy and short-chain beta-hydroxyacyl-CoA dehydrogenase (SCHAD) and citrate synthase (CS) enzyme activity. Training increased the mean lipid area density (P = 0.090), the number of IMCL droplets (P = 0.055), the number of IMCL droplets in contact with mitochondria (P = 0.010), the total mitochondrial area (P < 0.001), and the size of individual mitochondrial fragments (P = 0.006). Women had higher mean lipid area density (P = 0.030) and number of IMCL droplets (P = 0.002) before and after training, but higher individual IMCL area only before training (P = 0.013), compared with men. Women oxidized more fat (P = 0.027) and less carbohydrate (P = 0.032) throughout the study. Training increased Vo(2 peak) (P < 0.001), %fat oxidation (P = 0.018), SCHAD activity (P = 0.003), and CS activity (P = 0.042). In summary, endurance exercise training increased IMCL area density due to an increase in the number of lipid droplets, whereas the increase in total mitochondrial area was due to an increase in the size of individual mitochondrial fragments. In addition, women have higher IMCL content compared with men due mainly to a greater number of individual droplets. Finally, endurance exercise training increased the proportion of IMCL in physical contact with mitochondria.

3-Hydroxyacyl CoA Dehydrogenases↗

PubMed2006

Menstrual cycle phase and sex influence muscle glycogen utilization and glucose turnover during moderate-intensity endurance exercise.

Numerous studies from our and other laboratories have shown that women have a lower respiratory exchange ratio (RER) during exercise than equally trained men, indicating a greater reliance on fat oxidation. Differences in estrogen concentration between men and women likely play a role in this sex difference. Differing estrogen and progesterone concentrations during the follicular (FP) and luteal (LP) phases of the female menstrual cycle suggest that fuel use may also vary between phases. The purpose of the current study was to determine the effect of menstrual cycle phase and sex upon glucose turnover and muscle glycogen utilization during endurance exercise. Healthy, recreationally active young women (n = 13) and men (n = 11) underwent a primed constant infusion of [6,6-2H]glucose with muscle biopsies taken before and after a 90-min cycling bout at 65% peak O2 consumption. LP women had lower glucose rate of appearance (Ra, P = 0.03), rate of disappearance (Rd, P = 0.03), and metabolic clearance rate (MCR, P = 0.04) at 90 min of exercise and lower proglycogen (P = 0.04), macroglycogen (P = 0.04), and total glycogen (P = 0.02) utilization during exercise compared with FP women. Men had a higher RER (P = 0.02), glucose Ra (P = 0.03), Rd (P = 0.03), and MCR (P = 0.01) during exercise compared with FP women, and men had a higher RER at 75 and 90 min of exercise (P = 0.04), glucose Ra (P = 0.01), Rd (P = 0.01), and MCR (P = 0.001) and a greater PG utilization (P = 0.05) compared with LP women. We conclude that sex, and to a lesser extent menstrual cycle, influence glucose turnover and glycogen utilization during moderate-intensity endurance exercise.

Adult↗

PubMed2006

Transient caloric restriction in early adulthood hastens disease endpoint in male, but not female, Cu/Zn-SOD mutant G93A mice.

Long-term caloric restriction (CR) prolongs the lifespan in healthy insects, rodents, and nonhuman primates. We previously reported that long-term CR improves motor performance but hastens clinical onset of disease in an animal model of amyotrophic lateral sclerosis (G93A mice). G93A mice overexpress the mutant human Cu/Zn-SOD gene and show progressive lower motor neuron weakness and increased oxidative stress. To study short-term (15 days) CR in the same animal model, we investigated the effect of transient caloric restriction (TCR) on paw grip endurance, clinical onset, disease progression (time from clinical onset to endpoint), and lifespan. Starting at age 40 days, 32 separately caged G93A mice were randomly divided into two groups: ad libitum (AL, n = 17; 10 females, 7 males) and TCR (n = 15; 6 females, 9 males) with a diet equal to 60% of AL. When the TCR mice lost 30% of their weight they were offered food AL until endpoint, otherwise all TCR mice were provided food AL from age 55 days until endpoint (i.e., range of TCR = 13-15 days). Paw grip endurance started to decrease significantly at age 96 days compared with baseline values for all the groups. TCR males reached clinical onset 5 days sooner than TCR females. Disease progression was 8 days faster in TCR mice than AL mice and 6 days faster in male mice than female mice. The probability of survival was significantly different between the groups, with the TCR males having a faster rate of reaching endpoint than TCR females, AL males, and AL females. We conclude that TCR hastens clinical onset of disease and shortens the lifespan in male, but not female, G93A mice. Moreover, TCR hastens progress of disease but has no effect on paw grip endurance. The female sex is protective against the detrimental effects of short-term CR in G93A mice. Assuming we can extrapolate these results to humans, short-term CR should be avoided in patients with amyotrophic lateral sclerosis, especially men.

Amyotrophic Lateral Sclerosis↗

PubMed2005

No effect of short-term 17beta-estradiol supplementation in healthy men on systemic inflammatory responses to exercise.

Sex-based differences in inflammatory responses to exercise may be mediated by estrogen through increased muscle membrane stability and/or inhibited cytokine production. In this study, in vivo effects of estrogen on systemic inflammation-related responses to exercise were assessed in healthy men. In a double-blind, placebo-controlled, crossover design, 11 men cycled for 90 min at 65% Vo2 max after 8 days of 17beta-estradiol supplementation (ES; 2 mg/day) or placebo (PL; glucose polymer). After a 2-wk washout, exercise was repeated after 8 days on the alternate treatment. Blood was collected pre- and postexercise to determine IL-6, soluble intercellular adhesion molecule-1 (sICAM-1), neutrophil counts, and cortisol. Preexercise serum was assayed for sex hormones. ES increased estradiol (133+/-71 to 840+/-633 pmol/l, P=0.005) and reduced testosterone (19.9+/-3.7 to 16.1+/-3.9 nmol/l, P=0.007). Exercise increased cortisol (P=0.02), IL-6 (P<0.001) and neutrophil counts (P<0.001) with no influence on sICAM-1 (P=0.34) and no effect of ES on these changes. Postexercise IL-6 and neutrophil counts were correlated (r=0.58, P=0.005); postexercise IL-6 and cortisol (r=0.18, P=0.43) and postexercise cortisol and neutrophil counts (r=0.06, P=0.78) were not. Postexercise sICAM-1 was not correlated with the above variables (P>or=0.79). In conclusion, 8 days of ES in healthy men did not influence systemic inflammation-related responses to acute exercise. Future studies should investigate 17beta-estradiol effects on IL-6 production and neutrophil infiltration within skeletal muscle during and after exercise.

Adult↗

PubMed2005

17beta-estradiol supplementation decreases glucose rate of appearance and disappearance with no effect on glycogen utilization during moderate intensity exercise in men.

CONTEXT AND OBJECTIVE: Women use less carbohydrate during endurance exercise, as compared with men. In rodents, 17beta-estradiol (E2) supplementation robustly increases lipid use and lowers muscle and liver glycogen use during exercise. E2 supplementation has been found to influence substrate selection by decreasing glucose rate of appearance (Ra), disappearance (Rd), and metabolic clearance rate during exercise in humans; however, neither a change in total carbohydrate use nor a sparing of muscle glycogen was demonstrated. SUBJECTS AND METHODS: We investigated the effect of 8 d of E2 (2 mg/d) supplementation on glucose turnover and net muscle glycogen use in 11 men using a randomized, double-blind, placebo-controlled, crossover design. Subjects underwent primed constant infusion of [6,6-(2)H]glucose, and muscle biopsies were taken before and after 90 min of cycling at 65% maximal oxygen uptake. RESULTS: E2 supplementation decreased the respiratory exchange ratio (P = 0.03) and glucose Ra and Rd (both P = 0.04) during exercise, as compared with placebo. E2 supplementation lowered proglycogen (P < 0.05) and total glycogen (P = 0.04) concentration, as compared with placebo; however, there was no effect of E2 on net muscle glycogen use during exercise. CONCLUSIONS: These findings show that E2 supplementation alters fuel selection in exercising men by increasing lipid use and reducing carbohydrate use, glucose Ra (primarily liver glucose production), and Rd (primarily muscle glucose uptake). Furthermore, E2 reduces the basal level of total muscle glycogen, particularly the proglycogen form.

Adult↗

PubMed2005

Human sulfate kinetics.

Electrospray tandem mass spectrometry was used to determine steady-state serum and urinary inorganic sulfate and sulfate ester kinetic profiles of nine normal men after intravenous injection of the stable isotope sodium [34S]sulfate. Sulfate ester appearance was traced by eliminating inorganic sulfate from samples, followed by hydrolysis of sulfate esters to inorganic sulfate for analysis. Whole body inorganic sulfate turnover in steady state was calculated using standard tracer techniques. Rate of appearance and disappearance of inorganic sulfate was 841 +/- 49 micromol/h. Average urinary inorganic sulfate excretion was 609 +/- 41 micromol/h, and the whole body sulfation rate (total rate of disappearance minus rate of urinary excretion) was 232 +/- 36 micromol/h. Tracer-labeled sulfate esters appeared in serum and urine within 1 h of tracer injection. The kinetics of inorganic sulfate and sulfate esters were linked by means of a compartmental model. The appearance and excretion of sulfate esters accounted for approximately 50% of the total sulfation rate. These results indicate that human whole body sulfation accounts for approximately 27% of inorganic sulfate turnover and that extracellular inorganic sulfate is an important pool for intracellular sulfation. A substantial fraction of newly synthesized sulfate esters promptly enters the extracellular space for excretion in the urine.

Fasting↗

PubMed2005

Influence of gender, menstrual phase, and oral contraceptive use on immunological changes in response to prolonged cycling.

This study determined the influence of gender, menstrual phase (MP), and oral contraceptive (OC) use on immunological changes in response to endurance exercise. Twelve women and 11 men similar in age, aerobic power, and activity level cycled for 90 min at 65% maximal aerobic power. Women were OC users (n = 6) or nonusers (NOC) and cycled during the follicular (Fol) and the luteal (Lut) phases. Venous blood was collected before and after exercise to determine leukocyte counts, IL-6 concentrations, and cortisol. Higher resting levels of neutrophils (approximately 1.5-fold) and cortisol (approximately 2.5-fold) were found in OC vs. NOC and men. Exercise-induced immune cell count and IL-6 changes were similar between men and NOC, except for an approximately 38% greater lymphocyte response in NOC vs. men (P = 0.07). Neutrophil, monocyte, and lymphocyte responses to exercise during Lut in OC were greater than during Fol and also greater than the responses in men (P < or = 0.003). Changes in immune cell counts were consistently greater during Lut in OC vs. NOC, regardless of MP, but only neutrophil responses reached statistical significance (P = 0.01). The exercise-induced change in IL-6 was approximately 80% greater in NOC vs. OC during Fol (P = 0.06), but it was similar between these groups during Lut. Cortisol changes with exercise were not different between groups or MP. These results highlight the necessity to control for gender, and in particular OC use, when designing studies evaluating exercise and immunology.

Adult↗

PubMed2005

Estrogen supplementation reduces whole body leucine and carbohydrate oxidation and increases lipid oxidation in men during endurance exercise.

Healthy active men exhibit higher rates of carbohydrate (CHO) and leucine oxidation and lower rates of lipid oxidation compared with their female counterparts both at rest and during moderate intensity endurance exercise. We postulated that this reduced dependence on amino acids as a fuel source in women was due to the female sex hormone estrogen. In a randomized, double-blind, placebo-controlled, cross-over design, we investigated the effect of supplementing 12 recreationally active men with estrogen on whole body substrate oxidation and leucine kinetics at rest and during moderate intensity endurance exercise. Subjects cycled for 90 min at an intensity of 65% maximum O(2) consumption after 8 d of either estrogen supplementation (2 mg 17beta-estradiol/d) or placebo (polycose). After a 2-wk washout period, they repeated the test after 8 d of the alternate treatment. On the test day, after a primed continuous infusion of l-[(13)C]leucine, O(2) consumption, CO(2) production, steady-state breath (13)CO(2), and plasma alpha-[(13)C]ketoisocaproate enrichments were measured at rest and at 60, 75, and 90 min during exercise in the postabsorptive state. Exercise increased energy expenditure more than 5-fold, CHO oxidation more than 6-fold, lipid oxidation more than 4-fold, and leucine oxidation 2.2-fold (all P < 0.0001), whereas it decreased the ratio of lipid to CHO oxidation by 50-70% (P = 0.003) compared with values at rest. Estrogen supplementation decreased respiratory exchange ratio during exercise (P = 0.03). Estrogen supplementation significantly decreased CHO oxidation by 5-16% (P = 0.04) and leucine oxidation by 16% (P = 0.01), whereas it significantly increased lipid oxidation by 22-44% (P = 0.024) at rest and during exercise. We conclude that estrogen influences fuel source selection at rest and during endurance exercise in recreationally active men, characterized by a reduced dependence on amino acids and CHO and an increased reliance on lipids as a fuel source.

Adult↗

PubMed2005

Caloric restriction transiently improves motor performance but hastens clinical onset of disease in the Cu/Zn-superoxide dismutase mutant G93A mouse.

Caloric restriction (CR) prolongs lifespan in insects, rodents, and nonhuman primates, a process attributed to a reduction in oxidative stress. Transgenic mice that overexpress the mutant human Cu/Zn-superoxide dismutase (SOD1) gene (G93A mice) are an animal model of amyotrophic lateral sclerosis showing progressively lower motor neuron weakness and increased oxidative stress. We investigated the effect of CR on motor performance, clinical onset, disease progression, and lifespan in G93A mice. Starting at 40 days of age, 14 separately caged G93A mice were randomly divided into two groups: ad libitum (AL; n = 6) and calorie-restricted (CR; n = 8) with a diet equal to 60% of AL. The CR mice (mean +/- SEM: 14.0 +/- 0.7 g) weighed 31% less than the AL mice (20.3 +/- 1.0 g) (P = 0.0002). From 74 to 93 days of age, the CR mice performed better on the rotarod than the AL mice: fall time, P = 0.039; fall speed, P = 0.009. The CR mice had a faster rate of reaching clinical onset than the AL mice (hazard ratio = 4.3, P = 0.0006). The CR and AL mice reached clinical onset of disease at age 99 +/- 1 and 110 +/- 2 days, respectively (P = 0.0003), with no significant difference in disease progression. The CR mice tended to reach endpoint sooner than the AL mice (age-specific death: 125 +/- 3 vs. 133 +/- 3 days, respectively, P = 0.09). We conclude that CR diet transiently improves motor performance but hastens clinical onset of disease in G93A mice. These results suggest that CR diet is not a protective strategy for patients with amyotrophic lateral sclerosis (ALS) and hence is contraindicated.

Amyotrophic Lateral Sclerosis↗

PubMed2002

Effect of protein restriction on sulfur amino acid catabolism in insulin-dependent diabetes mellitus.

Persons with conventionally treated insulin-dependent diabetes mellitus (IDDM) appear to be impaired in their ability to reduce fed-state urea production appropriately in response to dietary protein restriction (Hoffer LJ, Taveroff A, and Schiffrin A. Am J Physiol 272: E59-E67, 1997). To determine whether these conclusions apply to whole body sulfur amino acid (SAA) catabolism, we used samples from this protocol to measure daily urinary sulfate excretion and fed-state sulfate production after a high-protein test meal before and after dietary protein restriction. Eight normal subjects and six IDDM subjects treated with twice-daily intermediate- and short-acting insulin consumed a mixed test meal containing 0.50 g protein/kg after adaptation to 4 days of high protein intake (1.28 g protein/kg body wt) and again after 5 days of dietary protein restriction (0.044 g/kg). Adaptation to protein restriction decreased daily urinary sulfate and urea-N excretion by approximately 80%. Over the first 24 h of protein restriction, urinary sulfate excretion decreased more than urea-N excretion for both the normal and IDDM subjects. Under conditions of a high prior protein intake, fed-state sulfate production was normal for the IDDM subjects; protein restriction reduced fed-state sulfate production by 51% (normal subjects) and 59% (IDDM subjects; not significant). We conclude that whole body SAA metabolism is normal in conventionally treated IDDM before and after dietary protein restriction. SAA catabolism, as measured by fed-state sulfate production, may be a convenient and useful method to determine the extent of whole body protein dysregulation in IDDM.

Adaptation, Physiological↗