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Biomedical subjects

M J Toth

Publications and source records attributed to M J Toth.

At least 55 records · Page 3Linked to original sources
PubMed1997

Daily energy expenditure in free-living heart failure patients.

We examined the hypothesis that weight loss in heart failure patients is associated with elevated daily energy expenditure. Twelve cachectic patients [age = 73 +/- 6 yr; weight loss = 15 +/- 6 kg; body mass index (BMI) = 21 +/- 5 kg/m2], 13 noncachectic patients (age = 67 +/- 5 yr; BMI = 27 +/- 5 kg/m2), and 50 healthy elderly controls (age = 69 +/- 6 yr; BMI = 26 +/- 4 kg/m2) were studied. Daily energy expenditure and it components were measured using doubly labeled water and indirect calorimetry and body composition by dual-energy X-ray absorptiometry. Fat mass and fat-free mass were lower (P < 0.05) in cachectic patients compared with noncachectic patients and healthy controls. Daily energy expenditure was lower (P < 0.05) in cachectic patients (1,870 +/- 347 kcal/day) compared with noncachectic patients (2,349 +/- 545 kcal/day) and healthy controls (2,543 +/- 449 kcal/day). Differences in daily energy expenditure were primarily due to lower (P < 0.05) physical activity energy expenditure in cachectic (269 +/- 307 kcal/day) and noncachectic patients (416 +/- 361 kcal/day) compared with healthy controls (728 +/- 374 kcal/day). A lower (P < 0.05) resting energy expenditure was also noted in cachectic patients (1,414 +/- 210 kcal/day) compared with noncachectic patients (1,698 +/- 252 kcal/day) and healthy controls (1,561 +/- 223 kcal/day). These findings show that daily energy expenditure is not higher, but significantly lower, in cachectic heart failure patients due to lower physical activity and resting energy expenditure. These results argue against the hypothesis that an abnormally elevated daily energy expenditure is associated with weight loss in heart failure.

Age Factors↗
PubMed1997

Racial differences in plasma leptin concentrations in obese postmenopausal women.

Leptin may play an important role in the regulation of body weight by influencing energy intake and expenditure. Differences in body composition, resting energy expenditure (REE), and physical activity between African-American and Caucasian women could be reflective of racial differences in plasma leptin concentrations. Thus, we examined racial differences in leptin levels and the relationships of leptin to body composition and resting metabolism in obese postmenopausal African-American (n = 28) and Caucasian (n = 29) women matched for level of body fat. African-American and Caucasian women were similar in age (64.1 +/- 1.3 vs. 63.2 +/- 1.0 yr), body weight (84.7 +/- 3.3 vs. 80.4 +/- 1.3 kg), adipose tissue mass (39.7 +/- 2.8 vs. 38.0 +/- 1.0 kg), waist to hip ratio (0.81 +/- 0.02 vs. 0.81 +/- 0.01), and maximal aerobic capacity (1.5 +/- 0.05 vs. 1.6 +/- 0.05 L/min). African-American women had greater lean tissue mass than Caucasian women (41.8 +/- 1.1 vs. 39.3 +/- 0.6 kg; P = 0.05). The leptin concentration was 20% lower in African-American than Caucasian women (36.0 +/- 4.8 vs. 45.8 +/- 3.5; P < 0.05), whereas REE values were similar. Leptin correlated strongly with percent body fat in African-American (r = 0.71; P < 0.0001) and Caucasian women (r = 0.61; P < 0.001) and with REE in African-American (r = 0.58; P < 0.001), but not Caucasian, women (r = 0.08). These findings suggest racial differences in plasma leptin levels and in leptin's role in the regulation of REE, which may play a role in the greater incidence of obesity in the African-American compared to the Caucasian population.

Adipose Tissue↗
PubMed1997

Free-living daily energy expenditure in patients with Parkinson's disease.

Previous studies have suggested that elevated resting energy expenditure contributes to weight loss in patients with Parkinson's disease (PD). Body weight is, however, ultimately determined by variation in daily energy expenditure and not just resting energy expenditure. Therefore, we examined the hypothesis that PD patients are characterized by elevated daily energy expenditure. Sixteen patients with levodopa responsive PD and 46 healthy elderly controls were characterized for daily energy expenditure and its components (resting and physical activity energy expenditure) using a combination of the doubly labeled water technique (over 10 days) and resting indirect calorimetry. Fat-free mass and fat mass were measured by dual energy x-ray absorptiometry. Results showed that fat mass and fat-free mass did not differ between groups. Daily energy expenditure was 15% lower (2214 +/- 460 vs. 2590 +/- 497 kcal/d; p < 0.01) in PD patients compared to controls. This was primarily due to lower physical activity energy expenditure (339 +/- 366 vs. 769 +/- 412 kcal/d; P < 0.01) in PD patients as resting energy expenditure was not different between groups (1655 +/- 283 vs. 1561 +/- 219 kcal/d). These results show that daily energy expenditure is lower in PD patients compared to healthy elderly, primarily due to reduced physical activity energy expenditure. These results argue against the hypothesis that an abnormally elevated daily energy expenditure contributes to weight loss in PD.

Aged↗
PubMed1997

Daily energy expenditure in free-living non-institutionalized Alzheimer's patients: a doubly labeled water study.

Weight loss is common in Alzheimer's disease (AD), but its pathogenesis is poorly understood. It is unclear whether an elevated daily energy expenditure contributes to the weight loss. We tested the hypothesis that daily energy expenditure is higher in AD patients compared to healthy elderly. Thirty AD (73 +/- 8 years; Mini-Mental State Examination score: 16 +/- 8) and 103 healthy elderly (69 +/- 7 years) were characterized for daily energy expenditure and its components (resting and free-living physical activity energy expenditure) from doubly labeled water and indirect calorimetry. Fat-free mass and fat mass were measured from dual energy X-ray absorptiometry. Fat-free mass tended to be lower in AD patients (45 +/- 9 kg) versus healthy elderly (49 +/- 10 kg; p = 0.07), whereas no differences were noted in fat mass between groups. Daily energy expenditure was 14% lower in AD (1901 +/- 517 kcal/d) compared to healthy elderly (2213 +/- 513 kcal/d; p < 0.001), due to lower resting (1287 +/- 227 versus 1418 +/- 246 kcal/d; p < 0.01) and physical activity energy expenditures (425 +/- 317 versus 574 +/- 342 kcal/d; p < 0.05). No differences in energy expenditure were noted between groups after controlling for differences in body composition. Daily energy expenditure was examined in a subgroup (n = 11) of AD patients who lost significant body weight (5.6 +/- 2.3 kg) within the past year. There was a lower daily energy expenditure in cachectic AD patients (1799 +/- 474 kcal/d) versus non-cachectic patients (1960 +/- 544 kcal/d) and healthy elderly (2213 +/- 513 kcal/d; p < 0.01). Similarly, no differences in energy expenditure were noted between groups after controlling for differences in body composition. We conclude that absolute levels of daily energy expenditure are lower in AD patients due to their lower body mass. However, after taking into account differences in body composition, daily energy expenditure in AD patients is appropriate for their metabolic size. The hypothesis that elevated daily energy expenditure contributes to weight loss in AD is not supported by these findings.

Absorptiometry, Photon↗
PubMed1997

Daily energy expenditure is related to plasma leptin concentrations in older African-American women but not men.

Recent research suggests that leptin may control body weight by regulating energy expenditure and energy intake in mice. To explore the possible role of leptin in the regulation of energy expenditure in humans, we used doubly-labeled water methodology to determine whether fasting plasma leptin concentrations were related to total daily energy expenditure (TEE) and its components, resting energy expenditure (REE) and physical activity energy expenditure (PAEE), in free-living older African-American men (n = 21) and women (n = 25). Plasma leptin concentrations were higher in women than men, even after the adjustment for differences in fat mass (28 +/- 3 ng/ml for women vs. 17 +/- 3 ng/ml for men; P < 0.01). The logarithm of plasma leptin concentrations correlated with fat mass in both women (r = 0.80) and men (r = 0.78) (P < 0.0001). After statistical adjustment for sex differences in fat-free mass and fat mass, women had lower TEE (22%) and REE (15%) (P < 0.01) and a trend (P = 0.08) toward lower PAEE, compared with men. After controlling for the effects of fat-free mass on energy expenditure, plasma leptin concentrations were related to REE (r = 0.68, P < 0.001) and tended to be related to TEE (r = 0.37, P = 0.07) in African-American women but not men (r = 0.18 and -0.03, respectively). Plasma leptin concentrations were not related to PAEE in either men or women. These results suggest that leptin may contribute to the regulation of TEE in older African-American women through its effects on resting energy metabolism, but the role of leptin in the regulation of energy expenditure is less apparent in older African-American men.

Black or African American↗
PubMed1997

Post-translational regulation of mevalonate kinase by intermediates of the cholesterol and nonsterol isoprene biosynthetic pathways.

To assess the potential for feedback inhibition by isoprene intermediates in the cholesterol and nonsterol isoprene biosynthetic pathway, we expressed human cDNAs encoding mevalonate kinase (MKase), phosphomevalonate kinase (PMKase), and mevalonate diphosphate decarboxylase (MDDase) as fusion proteins in Escherichia coli DH5alpha, and purified these proteins by affinity chromatography. Several phosphorylated and non-phosphorylated isoprenes were analyzed as inhibitors of the enzymes using a standard spectrophotometric assay. Of the three proteins, only MKase was inhibited through competitive interaction at the ATP-binding site. The intermediates studied (and their relative inhibitory capacity) were: geranylgeranyl-diphosphate (GGPP, C20) > farnesyl-diphosphate (FPP, C15) > geranyl-diphosphate (GPP, C10) > isopentenyl-diphosphate (IPP, C5) > or = 3,3-dimethylallyl-diphosphate (DMAPP, C5) > farnesol (C15) > dolichol-phosphate (DP, C(80-100)). Mevalonate-diphosphate, geraniol, and dolichol were not inhibitors. Our data further define the spectrum of physiologic inhibitors of MKase, and provide the first evidence for feedback inhibition of MKase by a nonsterol isoprene produced by the branched pathway, dolichol-phosphate. These results provide additional evidence that MKase may occupy a central regulatory role in the control of cholesterol and nonsterol isoprene biosynthesis.

Carboxy-Lyases↗
PubMed1996

Relationship between physical activity and HDL-cholesterol in healthy older men and women: a cross-sectional and exercise intervention study.

We used cross-sectional and exercise intervention studies to examine whether physical activity levels or increases in peak aerobic capacity (peak VO2) explain variation in high density lipoprotein cholesterol (HDL-C) levels in older men and women. In the cross-sectional study, 307 older individuals (169 men; 138 women; 67 +/- 7 years) were characterized for HDL-C, leisure time physical activity, peak VO2, body composition, body fat distribution and dietary intake. HDL-C was 19% higher (P < 0.001) in women (57 +/- 14 mg/dl) versus men (48 +/- 14 mg/dl). Thirty-two percent of the variation in HDL-C in older men was explained by the waist circumference (r2 = 16%), percent dietary intake of alcohol (r2 = 11%), and carbohydrate (r2 = 6%). Waist circumference was also the best predictor of HDL-C in older women, (r2 = 7%); with percent dietary intake of carbohydrate adding an additional 6% to the model. Neither peak VO2 nor leisure time physical activity were independent predictors of HDL-C. Statistical control for the aforementioned variables diminished, but did not abolish gender differences in HDL-C. Thirty-seven older individuals (23 men; 14 women) participated in a 2-month exercise program in which individuals by week eight were expending approximately 900 kcal per week in exercise energy expenditure. Subjects were maintained in energy balance throughout the exercise program. Endurance training significantly increased peak VO2 by 15% in both men and women, and by design, body composition and body fat distribution did not change. No changes in HDL-C levels were noted. In conclusion, variations in leisure time physical activity or increases in peak VO2 are not independent predictors of HDL-C levels in healthy older men and women. Instead, central adiposity, as estimated by the waist circumference, and to a lesser extent, dietary intake of carbohydrate and alcohol, are significant predictors of variation in plasma HDL-C levels. Furthermore, short-term exercise training, generating less than 900 kcal per week in exercise energy expenditure, in the absence of weight loss, fails to influence HDL-C levels.

Aged↗
PubMed1996

Energy expenditure and symptom severity in men with heart failure.

Our results demonstrate a graded increase in resting metabolic rate based on symptom severity as reflected in the New York Heart Association classification. This finding supports the hypothesis that clinical severity of illness corresponds to the magnitude of the increase in resting energy demands.

Aged↗
PubMed1996

Molecular cloning and expression of the cDNAs encoding human and yeast mevalonate pyrophosphate decarboxylase.

The importance of lowering serum cholesterol levels for the prevention of cardiovascular disease has been well documented. Because mevalonate pyrophosphate decarboxylase is a unique enzyme in the cholesterol biosynthetic pathway it is a potential therapeutic target for the treatment of hypercholesterolemia and other diseases. For this reason we cloned and expressed the cDNA for the human enzyme. We also cloned and expressed the yeast homolog using the human enzyme's similarity to a previously unidentified and incomplete genomic sequence. Northern blot analysis revealed a transcript of approximately 2 kilobases in a variety of human tissues. The recombinant human enzyme is a homodimer of 43-kDa subunits with a specific activity of 2.4 units/mg. Computer searches for similarity with known sequences showed that mevalonate pyrophosphate decarboxylase has little similarity to other proteins.

Amino Acid Sequence↗
PubMed1996

Purification of rat liver mevalonate pyrophosphate decarboxylase.

Mevalonate pyrophosphate decarboxylase was isolated from rat liver to 90% purity as judged by SDS-PAGE using Phenyl Sepharose, p-coumaric acid-Sepharose, Mono P, and Mono Q chromatography. Gel filtration chromatography of the crude extract determined the native enzyme to be near 100 kDa while SDS-PAGE of the purified enzyme showed a protein band at 45 kDa. This implies that the native rat liver enzyme is a homodimer which differs from the published report that the enzyme is a tetramer of 35 kDa subunits. We measured a specific activity of 4.6 units/mg and a KM for mevalonate pyrophosphate of 20 microM. These values are similar to those reported for the chicken liver and the pig liver enzymes, but differ from the published report of the rat liver enzyme.

Animals↗
PubMed1996

No evidence for a higher resting metabolic rate in noninstitutionalized Alzheimer's disease patients.

OBJECTIVE: It has previously been suggested that Alzheimer's disease patients have higher resting energy requirements than healthy individuals, which may contribute to their unexplained weight loss. We examined whether resting metabolic rate, the largest component of daily energy expenditure, is elevated in Alzheimer's patients compared with healthy older controls. DESIGN: Cross-sectional. SETTING: General Clinical Research Center and Baltimore VA Medical Center. PATIENTS: Twenty-five noninstitutionalized demented patients (74 +/- 8 years; mean +/- SD) with a wide range of Mini-Mental Examination scores (1 to 20) and 73 healthy older individuals (69 +/- 7 years). MEASUREMENTS: Resting metabolic rate was measured by indirect calorimetry, fat-free mass and fat mass by dual energy X-ray absorptiometry, and daily energy intake by food diaries. RESULTS: No differences in fat-free mass and fat mass were noted between Alzheimer's disease patients and healthy older controls. Resting metabolic rate was similar in Alzheimer's disease patients (5446 +/- 962 kJ/day) and healthy older individuals (5647 +/- 887 kJ/day). These results persisted when resting metabolic rate was statistically adjusted for differences in body composition and age. CONCLUSION: These results provide no evidence for an elevation in resting energy requirements in noninstitutionalized demented patients.

Absorptiometry, Photon↗
PubMed1996

Rates of free fatty acid appearance and fat oxidation in healthy younger and older men.

Alterations in the mobilization and oxidation of fat may partially account for age-related alterations in body composition. To investigate age-related alterations in fat metabolism, we compared basal rate of appearance of free fatty acids (FFAapp) and total body fat oxidation as measured by infusions of [14C] palmitate and indirect calorimetry, respectively, in 18 younger (23 +/- 1 yr) and 30 older (69 +/- 1 yr) men. We also examined whether age-related differences in body composition, body fat distribution, peak oxygen consumption, dietary intake, and/or fasting insulin levels may explain age-related variation in FFAapp and total body fat oxidation. The FFAapp showed a tendency to be higher in older compared with younger men (1,134 +/- 184 vs. 680 +/- 105 mu mol/min; P = 0.07), whereas total body fat oxidation was similar between groups (257 +/- 25 vs. 222 +/- 9 mu mol/min). The estimated rate of nonoxidative disposal of free fatty acids showed a tendency to be higher in the older (913 +/- 182 mu mol/min) than in younger men (423 +/- 103 mu mol/min; P = 0.06). Fat-free mass was the most significant predictor of FFAapp in younger (r = 0.63; P < 0.01) and older (r = 0.41; P < 0.05) men. These results suggest that older men recruit fatty acids from adipose tissue stores in excess of the energy needs of respiring tissue. However, variation in FFAapp between the age groups could not be explained by differences in body habitus or fasting insulin levels.

Adult↗
PubMed1996

Determinants of basal fat oxidation in healthy Caucasians.

In a retrospective study, we examined several determinants of basal fat oxidation in 720 healthy Caucasian volunteers. Adult men (n = 427) and women (n = 293) were characterized for resting energy expenditure and substrate oxidation by indirect calorimetry (after a 12-h overnight fast), peak O2 consumption by a treadmill test to exhaustion, body composition by hydrodensitometry, food intake from a 3-day food diary, and hormonal status by fasting hormone concentrations. Fat oxidation was negatively correlated with fat mass in men (r = -0.11; P < 0.05), but no statistical relationship was found in women. In a stepwise multiple regression analysis, fat oxidation was best predicted by peak O2 consumption and fat-free mass in men (model R2 = 0.142) and by free thyroxine, fat-free mass, and fasting insulin in women (model R2 = 0.153). Relative rates of fat oxidation (fat oxidation adjusted for differences in resting energy expenditure) were not correlated with fat mass in either gender. Women showed a lower rate of basal fat oxidation (both absolute and adjusted) than did men. Our results show that fat oxidation is not greater in individuals with a greater fat mass. Furthermore, our results support a sexual dimorphism in basal rates of fat oxidation.

Adult↗
PubMed1995

Changes in energy balance and body composition at menopause: a controlled longitudinal study.

OBJECTIVE: To describe the effects of menopause on resting metabolic rate, body composition, fat distribution, physical activity during leisure time, and fasting insulin levels. DESIGN: A longitudinal comparison of metabolic changes in women who experienced menopause with changes in age-matched women who did not experience menopause. SETTING: General clinical research center. PATIENTS: An initial cohort of 35 sedentary healthy premenopausal women (age range, 44 to 48 years). After 6 years of follow-up, 18 women had spontaneously stopped menstruating for at least 12 months and 17 women remained premenopausal. No women received hormone replacement therapy. RESULTS: Women who experienced menopause lost more fat-free mass than women who remained premenopausal (-3.0 +/- 1.1 kg and -0.5 +/- 0.5 kg, respectively), had greater decreases in resting metabolic rate (-103 +/- 55 kcal/d and -8 +/- 17 kcal/d) and physical activity during leisure time (-127 +/- 79 kcal/d and 64 +/- 60 kcal/d), and had greater increases in fat mass (2.5 +/- 2 kg and 1.0 +/- 1.5 kg), fasting insulin levels (11 +/- 9 pmol/L and -2 +/- 5 pmol/L), and waist-to-hip ratios (0.04 +/- 0.01 and 0.01 +/- 0.01) (P < or = 0.01 for all comparisons). Menopause did not affect energy intake, fasting glucose levels, or peak oxygen consumption. CONCLUSIONS: Natural menopause is associated with reduced energy expenditure during rest and physical activity, an accelerated loss of fat-free mass, and increased central adiposity and fasting insulin levels. These changes may indicate a worsening cardiovascular and metabolic risk profile.

Adipose Tissue↗
PubMed1995

Training status, resting metabolic rate, and cardiovascular disease risk in middle-aged men.

We investigated differences in resting metabolic rate (RMR) and cardiovascular disease risk factors among 86 middle-aged men (36 to 59 years) classified as resistance-trained ([RT] n = 19), aerobic-trained ([AT] n = 37), or untrained ([UT], n = 30) according to habitual exercise patterns. RMR, body composition, body fat distribution, supine blood pressure, maximal aerobic capacity (VO2max), plasma lipid levels, and fasting levels of insulin, glucose, and thyroid hormones were measured. We found that RMR, adjusted for differences in fat-free mass, showed a tendency to be greater in AT men as compared with RT men (P = .09) and was greater in AT men as compared with UT men (P < .05). No differences in RMR were noted between RT and UT men. UT men had higher values for total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C), and the insulin to glucose ratio and lower values for high-density lipoprotein cholesterol (HDL-C) (all P < .01) as compared with RT and AT men, whereas no differences in these variables were noted between RT and AT men. Supine diastolic blood pressure was lower in RT men as compared with both AT and UT men. Stepwise regression analysis showed that variations in body fatness accounted for the greatest variation in fasting lipid profile, blood pressure, and the insulin to glucose ratio among groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1995

Mathematical ratios lead to spurious conclusions regarding age- and sex-related differences in resting metabolic rate.

Resting metabolic rate (RMR) data have been normalized by dividing RMR by fat-free mass (FFM) (ie, ratio method), or by using a regression-based approach. We compared both data-normalization procedures on age- and sex-related differences in RMR. The ratio method showed no differences in adjusted RMR between older men (0.084 +/- 0.004 kJ.FFM-1.min-1) and younger men (0.082 +/- 0.003 kJ.FFM-1.min-1), whereas analysis of covariance showed a lower (P < 0.01) adjusted RMR in older men (4.81 +/- 0.04 kJ/min) than in younger men (5.14 +/- 0.04 kJ/min). In another example, the ratio method showed that women had a higher (P < 0.05) adjusted RMR (0.10 +/- 0.004 kJ/min) than did men (0.08 +/- 0.003 kJ/min), whereas analysis of covariance showed a lower (P < 0.01) adjusted RMR in women (4.45 +/- 0.03 kJ/min) than in men (4.62 +/- 0.03 kJ/min). The ratio method provides misleading conclusions regarding sex- and age-related differences in RMR when compared with a regression-based approach.

Adult↗
PubMed1995

Sarcopenia in aging humans: the impact of menopause and disease.

We examine the association of the menopause transition, congestive heart failure, and Parkinson's disease on body composition and energy expenditure. We present evidence suggesting that the normal menopausal transition is associated with accelerated loss of fat-free mass, a decline in resting metabolic rate, and increased central body fatness. Second, we show that the cardiac cachexia associated with heart failure is partially due to an elevated level of energy expenditure. Despite having a lower quantity of fat-free mass, congestive heart failure patients have a higher resting metabolic rate (approximately 283 kcal/d) for their metabolic size than healthy elderly. The elevated level of resting energy expenditure probably contributes to their unexplained weight loss. Parkinson's patients experience muscular rigidity and tremor which could contribute to inappropriately high levels of energy expenditure and difficulty in maintaining body weight and composition. We examined resting metabolic rate and body composition in eight Parkinson's patients and 34 healthy age-matched controls. Parkinson's patients showed lower levels of fat-free mass (approximately 6 kg), but similar resting metabolic rates (1601 +/- 250 kcal/d) versus healthy controls (1671 +/- 212 kcal/d), suggesting a hypermetabolic state. A re-examination of daily energy needs and the metabolic factors contributing to periods of energy imbalance during the menopausal transition and in several disease states may be a prerequisite to offsetting accelerated sarcopenia.

Adipose Tissue↗