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Biomedical subjects

E Ravussin

Publications and source records attributed to E Ravussin.

At least 109 records · Page 6Linked to original sources

Gender differences in muscle sympathetic nerve activity: effect of body fat distribution.

Muscle sympathetic nerve activity (MSNA) has been correlated with percent body fat (%BF) in males. Because MSNA is typically lower and %BF higher in females, we tested whether this relationship could be generalized to females. Because abdominal-visceral body fat in men may be responsible for elevated sympathetic activity, we hypothesized that an estimate [waist-to-thigh ratio (W/T)] would correlate positively with MSNA in both genders and account for higher MSNA in males. Microneurography, hydrodensitometry, and W/T measures were obtained in 14 males and 14 females with a large range of %BF and W/T. Regression analyses revealed positive correlations between MSNA and %BF in males (r = 0.55, P = 0.04) and in females (r = 0.63, P = 0.02), with no difference in the slopes of the regression lines but a higher intercept in males (P < 0.01). When genders were pooled, MSNA and W/T were correlated (r = 0.68, P < 0.0001); this positive correlation was also found in males (r = 0.57, P = 0.04) but not as strongly in females (r = 0.49, P = 0.07). Forward stepwise multiple-regression analysis using %BF, W/T, gender, and age indicated that W/T was the primary factor related to MSNA (R2 = 0.46); the other factors were not independent predictors. It is concluded that %BF is related to MSNA in both males and females but that the regression line is shifted downward in females because of lower levels of MSNA. W/T is a better correlate of MSNA than %BF and partially explains the higher MSNA in males. These findings may be relevant to the cardiovascular and metabolic disease risk associated with abdominal obesity.

Abdomen↗

Effects of glucocorticoids on energy metabolism and food intake in humans.

The effect of glucocorticoid administration on energy metabolism and food intake was studied in 20 healthy, nondiabetic Caucasian male volunteers [27 +/- 5 (SD) yr, 72 +/- 9 kg, 20 +/- 7% body fat] randomly and blindly assigned to glucocorticoid (methylprednisolone, METH; n = 10) or placebo (PLAC; n = 10) treatment. Each subject was studied twice: during a weight maintenance diet and during ad libitum food intake. Energy metabolism was measured by indirect calorimetry and food intake by an automated food-selection system. Twenty-four-hour urinary norepinephrine excretion (24-h NE) was used as an estimate of sympathetic nervous system activity. During weight maintenance, METH intravenous infusion (125 mg/30 min) increased energy expenditure compared with PLAC, and after 4 days of oral therapy, METH (40 mg/day) decreased 24-h NE and increased energy expenditure compared with PLAC. During ad libitum food intake, after 4 days of METH (40 mg/day) or PLAC oral therapy, both groups increased their energy intake over weight maintenance, but the increase was significantly larger in the METH group compared with the PLAC group (4,554 +/- 1,857 vs. 2,867 +/- 846 kcal/day; P = 0.04). Our data suggest that therapeutic doses of glucocorticoids induce obesity mostly by increasing energy intake, an effect which may be related to the ability of glucocorticoids to act directly or indirectly on the central regulation of appetite.

Administration, Oral↗

Gender does not influence sympathetic neural reactivity to stress in healthy humans.

Previous data support the idea of heightened sympathetically mediated cardiovascular reactivity in males. However, definitive conclusions cannot be made because of inconsistent reports, possibly stemming from imprecise measurement of sympathetic activity and/or failure to equate the stress stimuli between genders. The present study tested the hypothesis that males exhibit heightened sympathetic reactivity that is associated with heightened cardiovascular and plasma catecholamine responses. In 37 healthy adults (20 males, 17 females: age = 20-42 yr), direct recordings of skeletal muscle sympathetic nerve activity (MSNA), plasma catecholamines, heart rate, blood pressure, and perceived stress were measured before and during three laboratory stressors (isometric handgrip, cold pressor, and mental arithmetic). MSNA, catecholamine, and cardiovascular reactivity (defined as change from rest) were not consistently different between genders. For the isometric handgrip, when expressed as absolute unit changes, males had larger MSNA responses (P < 0.01), which were partially explained by greater contraction force; they did not differ in terms of percent change from baseline or in perceived stress. The responses to the cold pressor and mental arithmetic tasks were similar between genders. These findings indicate that stress-evoked vasoconstrictor neural excitation and the associated increases in blood pressure are not consistently influenced by gender.

Adult↗

A comparative study of different means of assessing long-term energy expenditure in humans.

We compared three independent techniques for measurement of total energy expenditure (TEE) in human subjects: 1) weight-maintaining energy intake (dietTEE), 2) 24-h chamber calorimetry (chamberTEE), and 3) differential elimination rates 2H2O and H(2)18O (isotopeTEE). Twenty-three healthy adult in-patients [19 never obese (NO), 2 obese (OB), and 2 formerly-obese (RO); 9 female, 14 malel] ingested a liquid formula diet (40% of calories as fat, 45% carbohydrate, 15% protein), the volume of which was adjusted until body weight was stable for at least 14 days. Body composition was then determined by hydrodensitometry, isotope dilution, and dual photon beam absorptiometry (DXA). The thermic effect of feeding (TEF) and resting energy expenditure [REE; measured before arising (dietREE) and after arising (chamberREE)] were determined by indirect calorimetry. Non-resting energy expenditure (NREE) was calculated as NREE = TEE - (REE + TEF). Subjects then gained or lost 10% of their body weight and were restudied as described above. All measures of TEE were significantly correlated (dietTEE vs. chamberTEE r2 = 0.75; dietTEE vs. isotopeTEE r2 = 0.88; isotopeTEE vs. chamberTEE r2 = 0.73; P < 0.0001). ChamberTEE (mean +/- SE = 2,107 +/- 64 kcal/day) was approximately 20% lower than either dietTEE (2,536 +/- 94 kcal/day, P < 0.0001) or isotopeTEE (2,564 +/- 83 kcal/day, P < 0.0001). When data were normalized to metabolic mass, weight gain of 10% was associated with significant increases in dietTEE (P < 0.005) and isotopeTEE (P < 0.05) but not chamberTEE; weight loss of 10% was associated with significant reductions in dietTEE (P < 0.005) and isotopeTEE (P < 0.05) but not chamberTEE. We conclude that measures of energy expenditure obtained in a highly controlled environment by caloric titration (dietTEE) or differential excretion rates of 2H2O and H(2)18O (isotopeTEE) are not significantly different and that measurements of TEE obtained in a respiratory chamber (chamberTEE) are significantly lower than dietTEE or isotopeTEE, probably largely due to limitations on physical activity in the chamber.

Adult↗

Effects of acute hyperinsulinemia on plasma leptin concentrations in insulin-sensitive and insulin-resistant Pima Indians.

Leptin, a recently discovered protein produced in adipocytes, may be important in the regulation of body energy stores. In humans, leptin is present in the circulation in direct proportion to the amount of body fat. In rodents, insulin seems to regulate the production of leptin, but there is only limited evidence that this occurs in humans. We, therefore, measured plasma leptin concentrations in 13 insulin-sensitive and 13 insulin-resistant Pima Indians at baseline, at the end of 100 min of physiologic hyperinsulinemia (mean plasma insulin = 563 pmol/L) and after a further 100 min of supraphysiologic hyperinsulinemia (mean plasma insulin = 11,910 pmol/L), during a 2-step hyperinsulinemic-euglycemic glucose clamp. At baseline, plasma leptin concentrations were directly related to percent body fat, determined by hydrodensitometry (r = 0.85, P < 0.0001). After adjusting for percent body fat, there were no differences in fasting plasma leptin concentrations between insulin-sensitive and insulin-resistant subjects. Plasma leptin concentrations did not change in response to insulin in either the insulin-sensitive or insulin-resistant subjects. These results suggest that insulin does not acutely regulate plasma leptin concentrations in humans.

Acute Disease↗

Absence of mutations in the human OB gene in obese/diabetic subjects.

The product of the obese (ob) gene, leptin, is a secreted protein that is important in the regulation of body weight. Mice with mutations in the ob gene are obese and diabetic and manifest reduced physical as well as metabolic activity. In this study, we tested the possibility that mutations in the OB gene may contribute to human obesity. We report the isolation and partial sequence of the human OB gene and the screening of 105 obese patients for mutations in the protein coding sequence using the technique of single-strand conformational polymorphism. No coding sequence polymorphism was found, suggesting that mutations in the coding sequence of the OB gene do not constitute a common cause of increased body weight in humans. We also identified a highly polymorphic simple dinucleotide repeat DNA polymorphism in this gene that will be useful for genetic studies.

Amino Acid Sequence↗

Absence of linkage of obesity and energy metabolism to markers flanking homologues of rodent obesity genes in Pima Indians.

The homologues of single genes that cause obesity in rodents are suggested as candidate genes for modulation of body composition in humans. Among these genes are the four mouse mutations-diabetes (db), obesity (ob), tubby (tub), and yellow agouti (Ay). Variation in the human counterparts to these genes (OB, DB, TUB, and ASP, respectively) may contribute to human obesity, which is thought to have a substantial genetic component. To initially assess the potential contribution of these genes to human obesity, we examined polymorphic DNA markers that, by virtue of syntenic relationships to appropriate regions of the mouse genome, should be closely linked to the human counterparts of these genes. Using combined data from 716 Pima Indians comprising 217 nuclear families, we have tested a number of polymorphic microsatellite markers (three at DB, two at OB, five at TUB, and three at ASP) for sib-pair linkage to BMI, percentage body fat, resting metabolic rate, 24-h energy expenditure, and 24-h respiratory quotient. No significant linkages were found in an analysis of all sibships or in an analysis restricted to discordant sib pairs.

Adipose Tissue↗

Dual energy X-ray absorptiometry: inter-machine variability.

OBJECTIVE: Dual-energy X-ray absorptiometry (DEXA) is rapidly becoming the method of choice for body composition measurements. We tested inter-machine variability because large differences in body composition measurements between different DEXA machines have recently been reported. DESIGN: Comparison of total body scans using 2 DEXA machines from the same manufacturer (DPX-L; Lunar Co, Madison, WI) on 10 volunteers (5M/5F). RESULTS: We observed statistically significant differences between the 2 machines for all mean values of body composition variables as a result of a systematic underestimation of bone mineral and overestimation of fat tissue by one machine vs the other. However, the magnitude of the observed differences was small (namely bone mineral +68 +/- 57 g; percent body fat -1.7 +/- 1%, Mean +/- s.d.). CONCLUSION: Differences do exist in the performances of 2 DEXA machines from the same manufacturer. Although the differences reported in the present study are small, emphasis should be given in pre-testing machines when multiple apparatuses are used in a study. Also, because the observed error was systematic, randomized designs are necessary when more than one DEXA machine is used in longitudinal/intervention study. Better yet, manufacturers of DEXA machine should standardize their equipment to ensure the best consistency between machines.

Absorptiometry, Photon↗

A high concentration of fasting plasma non-esterified fatty acids is a risk factor for the development of NIDDM.

To assess the role of fasting plasma non-esterified fatty acids (NEFA) in the development of non-insulin-dependent diabetes mellitus (NIDDM), data were analysed from annual examinations of 190 non-diabetic Pima Indians. Glucose tolerance was measured by a 75-g oral glucose tolerance test, insulin action by a euglycaemic hyperinsulinaemic (40 mU x m-2 x min-1) clamp and in vitro lipolysis using isolated abdominal fat cells. After a mean follow-up period of 4.0 +/- 2.4 years (mean +/- SD), 47 subjects developed NIDDM. Risk factors for NIDDM were estimated by proportional-hazards analysis and risk ratios (RR) with 95% confidence intervals (95% CI) calculated at the 90th and 10th percentile of the predictor variables. A large average fat-cell volume was predictive of NIDDM (RR=2.4; 95% CI=1.2-4.8) independent of age, sex, percent body and body fat distribution. A high fasting plasma NEFA concentration was also a risk factor for NIDDM (RR=2.3; 95% CI=1.1-4.7) independent of sex, percent body fat, waist/thigh ratio, insulin-mediated glucose uptake and fasting triglyceride concentration. We conclude that large fat cells and the resulting increased plasma NEFA concentrations are risk factors for the development of NIDDM.

Adipocytes↗

Metabolic differences and the development of obesity.

Studies, such as those on Pima Indians, have shown that metabolic factors are involved in the development of obesity and that being overweight is not simply a result of "sloth and gluttony." However, the environment also affects the development of obesity. Among individuals in a given environment, the variability in body size is influenced by genetically determined responses to that environment. People with a low metabolic rate (adjusted for body size and composition) are prone to weight gain, whereas those with a high level of spontaneous physical activity are less likely to become obese. Similarly, individuals with a high 24-hour respiratory quotient (RQ) are more likely to gain weight than those with a low RQ. Insulin sensitivity (not insulin resistance) is another metabolic predictor of obesity. Genetic linkage studies suggest a number of genes are linked to the development of obesity. By sibling-pair linkage analysis, tumor necrosis factor-alpha (TNF-alpha) was found to be linked to the percentage of body fat, and other studies have shown that fat cell production of TNF-alpha is greater in obese individuals.

Arizona↗

Leptin levels in human and rodent: measurement of plasma leptin and ob RNA in obese and weight-reduced subjects.

Leptin, the gene product of the obese gene, may play an important role in regulating body weight by signalling the size of the adipose tissue mass. Plasma leptin was found to be highly correlated with body mass index (BMI) in rodents and in 87 lean and obese humans. In humans, there was variability in plasma leptin at each BMI suggesting that there are differences in its secretion rate from fat. Weight loss due to food restriction was associated with a decrease in plasma leptin in samples from mice and obese humans.

Adult↗

Thermic effect of food in humans: methods and results from use of a respiratory chamber.

During the past two decades, many investigators have measured the thermic effect of food (TEF) in humans and have speculated on its role in the development of obesity. In this study we compared different ways of computing TEF from daily energy expenditure measurements in a respiratory chamber, evaluated the determinants of TEF, and more importantly assessed for the first time the relation between TEF and change in body weight. In 471 subjects, TEF was 1697 +/- 857 kJ/d (mean +/- SD), ie, 18 +/- 9% of energy intake. In 114 subjects studied more than once, intraindividual TEF variability was very high (CV = 48%). TEF correlated positively with the level of spontaneous physical activity (SPA) and negatively with fasting plasma glucose and insulin concentrations. TEF correlated inversely with age (males only) and body weight, percent body fat, and waist-to-hip ratio (females only). The level of SPA and fasting plasma glucose concentration were the only significant determinants of TEF, explaining 15% of its variance. In 137 subjects in whom body weight was measured > or = 6 mo after TEF measurement (mean follow-up duration of 2.9 +/- 1.7 y), a low TEF was not predictive of body weight gain. We conclude that, despite the low reproducibility of TEF from use of a respiratory chamber, data in a large number of subjects suggest that TEF is increased by higher SPAs and that insulin resistance is associated with a low TEF. More important, longitudinal data indicate that the variability in TEF is not associated with changes in body weight.

Adolescent↗

Use of dual-energy X-ray absorptiometry in obese individuals.

Dual-energy X-ray absorptiometry (DXA) provides precise measurements of body composition in humans. Because its use in obese subjects is limited by the size of the scanning area, we explored the possibility of estimating whole-body composition from DXA half-body scans. Body composition of 183 subjects with a wide range of body sizes [body mass index (BMI; in kg/m2) of 17.7 - 52.8] was assessed by DXA and hydrodensitometry. Subjects fitting in the DXA scanning area (group A, n = 156) were scanned once whereas subjects exceeding it (group B, n = 27) were scanned twice, once for each side of the body. When body-composition results for the right and left sides were compared, only minimal differences between the two sides of the body were found in both groups. Least-squares-regression analysis of whole-body composition by hydrodensitometry on DXA gave the following results: percent body fat, r2 = 0.89 (SEE = 4.1%); fat-free mass, r2 = 0.89 (SEE = 3.72 kg); and fat mass, r2 = 0.95 (SEE = 3.57 kg). Similar r2 values and SEEs were obtained for percent body fat when only results from DXA half-body scans of all subjects were considered: right side, r2 = 0.90 (SEE = 4.1%); and left side, r2 = 0.89 (SEE = 4.2%). The error in predicting body composition by hydrodensitometry from DXA whole- or half-body scans was not affected by the subject's body size and/or scanning technique. In conclusion, our results indicate that half-body scan values by DXA accurately predict whole-body composition.

Absorptiometry, Photon↗

Energy metabolism in weight-stable postobese individuals.

A low metabolic rate for a given body size and body composition and a low ratio of fat to carbohydrate oxidation predict body weight gain. Such metabolic traits could also explain, in part, the propensity of previously obese (postobese) individuals to regain weight after dieting. We studied 11 postobese volunteers (4 males, 7 females; aged 43 +/- 13 y, weighing 80.6 +/- 10.2 kg, with 30 +/- 7% body fat; x +/- SD) who lost 57 +/- 38 kg (23-139 kg) over 14 +/- 12 mo (6-48 mo) on various diet programs and had maintained this weight loss for > or = 2 mo (2-72 mo; 21 +/- 27 mo). After > or = 2 d of a weight-maintenance diet on a metabolic ward, 24-h energy expenditure and ratio of fat to carbohydrate oxidation were measured in a respiratory chamber. Compared with a control group (n = 110) with similar physical characteristics (aged 43 +/- 14 y, weighing 79.5 +/- 11.4 kg, with 30 +/- 12% body fat), [sequence: see text] postobese individuals had similar energy expenditures adjusted for fat-free mass, fat mass, age, and sex, but significantly higher respiratory quotients over 24 h (0.883 +/- 0.026 compared with 0.863 +/- 0.024, P < 0.01) and during sleep, 10 h after the last meal (0.894 +/- 0.063 compared with 0.845 +/- 0.055). These results suggest that postobese individuals have low rates of fat oxidation that may explain their propensity to regain weight.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗

Ad libitum food intake on a "cafeteria diet" in Native American women: relations with body composition and 24-h energy expenditure.

Epidemiologic studies consistently report associations between obesity and dietary fat but not total energy intake. We measured ad libitum food intake in a laboratory setting and evaluated its relation to body weight and composition, energy expenditure, and macronutrient utilization in 28 women of Pima-Papago heritage (aged 27 +/- 7 y, 85.3 +/- 19.0 kg, 44 +/- 6% body fat; means +/- SD). All women were studied during the follicular phase of the menstrual cycle. After a 4-d weight-maintenance period, the volunteers selected their food for 5 d from computerized vending machines offering a variety of familiar and preferred foods, ie, a "cafeteria diet". Twenty-four-hour energy expenditure and substrate oxidation were measured in a respiratory chamber on the 4th d o weight maintenance and the 5th d of ad libitum intake. Average ad libitum intake was 13,732 +/- 4238 kJ/d (11 +/- 1% protein, 40 +/- 1% fat, 49 +/- 4% carbohydrate), ie, moderate overeating by 27 +/- 37% above weight maintenance requirements (range: -27% to 124%). Percent body fat correlated with daily energy intake (r = 0.53, P < 0.01), the degree of overeating (r = 0.41, P < 0.05), and the selection of a diet higher in fat and lower in carbohydrate (r = 0.70 and r = -0.63, respectively, P < 0.001). Excess carbohydrate intake caused an increase in carbohydrate oxidation (r = 0.51, P < 0.01), whereas excess fat intake resulted in a decrease in fat oxidation (r = -0.53, P < 0.01) and thus a positive fat balance of 85 +/- 65 g/d. The positive relations among degrees of obesity, dietary fat intake and overeating, and the fact that dietary fat does not induce fat oxidation, support the hypothesis that dietary fat promotes obesity in women.

Adult↗

Linkage between obesity and a marker near the tumor necrosis factor-alpha locus in Pima Indians.

Because tumor necrosis factor-alpha (TNF-alpha) expression is increased in adipose tissue of both rodent models of obesity and obese humans, it has been considered as a candidate gene for obesity. Pima Indians were scored for genotypes at three polymorphic dinucleotide repeat loci (markers) near the gene TNF-alpha at 6p21.3. In a sib-pair linkage analysis, percent body fat, as measured by hydrostatic weighing, was linked (304 sib-pairs, P = 0.002) to the marker closest (10 kb) to TNF-alpha. The same marker was associated (P = 0.01) by analysis of variance with BMI. To search for possible DNA variants in TNF-alpha that contribute to obesity, single stranded conformational polymorphism analysis was performed from 20 obese and 20 lean subjects. Primer pairs were designed for the entire TNF-alpha protein coding region and part of the promoter. Only a single polymorphism located in the promoter region was detected. No association could be demonstrated between alleles at this polymorphism and percent body fat. We conclude that the linkage of TNF-alpha to obesity might be due to a sequence variant undetected in TNF-alpha or due to a variant in some other closely linked gene.

Adolescent↗

Influence of age, sex, and insulin on osteoblast function: osteoblast dysfunction in diabetes mellitus.

The osteoblast function was evaluated in normal and diabetic children and adults by measurements of the serum concentration of the carboxy-terminal extension peptide of procollagen (PICP), total and skeletal alkaline phosphatase (ALP), and osteocalcin. Moreover, the osteoblast-stimulating growth factor, insulin-like growth factor I (IGF-I), was measured in the same samples. In normal children (n = 420; age, 5-20 yr), a marked pubertal increase of serum IGF-I (peak values at age 14-16 yr in both sexes), osteocalcin, and total and skeletal ALP (peak values earlier in girls than in boys) and a small increase in PICP were observed. All osteoblast markers and IGF-I were markedly lower in normal adults (n = 229; age, 21-69 yr) than in children. All osteoblast parameters showed a high degree of correlation (P < 0.001) with each other. In adolescents (n = 104) treated for insulin-dependent diabetes mellitus (IDDM), serum IGF-I (-19%), osteocalcin (-28%), and skeletal ALP (-28%) were markedly decreased, whereas total ALP was significantly increased (29%), and serum PICP remained normal. In adult IDDM (n = 125), both serum IGF-I (-41%) and osteocalcin (-24%) were decreased, but skeletal ALP and PICP remained normal. A similar abnormality in serum IGF-I and osteocalcin was observed in white (n = 61) and Pima Indian (n = 16) non-IDDM patients. The concentration of skeletal ALP was highly significantly correlated (r > or = 0.9) with total ALP in both normal and diabetic subjects, but the slope of the regression was significantly different, indicating the presence of other, probably intestinal, ALP in all types of diabetes. In conclusion, the osteoblast function is significantly decreased in diabetic patients, which can best be characterized as a maturation defect, since the early osteoblast marker, PICP, remained normal in all types of diabetes, whereas a later marker, skeletal ALP, is frankly abnormal only in diabetic children. The most mature osteoblast marker, osteocalcin, is decreased in all types of diabetes irrespective of age.

Adolescent↗