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Biomedical subjects

E Ravussin

Publications and source records attributed to E Ravussin.

At least 37 records · Page 2Linked to original sources
PubMed2001

Body mass index as a measure of adiposity in children and adolescents: relationship to adiposity by dual energy x-ray absorptiometry and to cardiovascular risk factors.

Body mass index is widely used as a measure of adiposity in adults, but its use in children and adolescents is controversial. We assessed body mass index as a measure of adiposity in children and adolescents between the ages of 5 and 20 yr examined as part of the NIH survey of health in the Pima Indian population. Body mass index (measured in 985 subjects and analyzed in 3 age groups: 5-9, 10-14, and 15-19 yr, in both sexes) was compared cross-sectionally to percent fat and fat mass derived from dual energy x-ray absorptiometry and to fasting and 2-h plasma glucose, systolic and diastolic blood pressures, cholesterol, high density lipoprotein cholesterol, fasting insulin, and triglycerides. Body mass index was strongly correlated in all age groups to both percent fat (r = 0.83-0.94; for each group, P < 0.0001) and fat mass (r = 0.96-0.98; P < 0.0001). The relationship of body mass index to percent fat was different in males and females; differences were more marked in older age groups. Body mass index, percent fat, and fat mass showed similar degrees of correlation to metabolic measures in childhood. Body mass index is strongly associated with measures of adiposity derived from dual energy x-ray absorptiometry. Both measures show similar associations with cardiovascular risk factors in Pima Indian children.

Absorptiometry, Photon↗
PubMed2001

Plasma ghrelin concentration and energy balance: overfeeding and negative energy balance studies in twins.

Central (intracerebral ventral) and peripheral (subcutaneous and intraperitoneal) administration of ghrelin causes obesity in rodents by increasing food intake and decreasing fat oxidation. Recent studies in humans have shown that plasma ghrelin concentration was inversely related to body fat and was lower in Pima Indians, a population susceptible to obesity. Whether ghrelin plays a role in the etiology of obesity in humans is unknown. We, therefore, measured plasma ghrelin concentration before and after two interventions in monozygotic twins previously studied at Laval University, Quebec City. Twelve pairs of monozygotic twins were overfed by 84,000 kcal over a 100-day period, whereas another seven pairs of monozygotic twins were submitted to a 53,000 kcal negative energy balance induced by exercise over a 93-day period. At baseline, for all the subjects, plasma ghrelin concentration was negatively correlated with body mass and body fatness (r varying from 0.36 to 0.45). The intraclass coefficient for the twin resemblance (r(I) = 0.75; p = 0.006) indicated that plasma ghrelin concentration is a familial trait. In response to the 100-day intervention, plasma ghrelin exhibited a non-significant decrease of 61 +/- 30 fmol/l (p = 0.18) with overfeeding and a non-significant increase of 58 +/- 34 fmol/l (p = 0.17) with negative energy balance. However, there was no relationship between baseline plasma ghrelin concentration and the magnitude of body weight change in both interventions. These first experimental data under "clamped energy balance conditions" do not provide evidence that plasma ghrelin is involved in the etiology of human obesity. However, studies in free-living individuals are needed to clarify this question.

Adipocytes↗
PubMed2001

Circulating ghrelin levels are decreased in human obesity.

Ghrelin is a novel endogenous natural ligand for the growth hormone (GH) secretagogue receptor that has recently been isolated from the rat stomach. Ghrelin administration stimulates GH secretion but also causes weight gain by increasing food intake and reducing fat utilization in rodents. To investigate the possible involvement of ghrelin in the pathogenesis of human obesity, we measured body composition (by dual X-ray absorption) as well as fasting plasma ghrelin concentrations (radioimmunoassay) in 15 Caucasians (8 men and 7 women, 31+/-9 years of age, 92+/-24 kg body wt, and 29+/-10% body fat, mean +/- SD) and 15 Pima Indians (8 men and 7 women, 33+/-5 years of age, 97+/-29 kg body wt, and 30+/-8% body fat). Fasting plasma ghrelin was negatively correlated with percent body fat (r = -0.45; P = 0.01), fasting insulin (r = -0.45; P = 0.01) and leptin (r = -0.38; P = 0.03) concentrations. Plasma ghrelin concentration was decreased in obese Caucasians as compared with lean Caucasians (P < 0.01). Also, fasting plasma ghrelin was lower in Pima Indians, a population with a very high prevalence of obesity, compared with Caucasians (87+/-28 vs. 129+/-34 fmol/ml; P < 0.01). This result did not change after adjustment for fasting plasma insulin concentration. There was no correlation between fasting plasma ghrelin and height. Prospective clinical studies are now needed to establish the role of ghrelin in the pathogenesis of human obesity.

Adult↗
PubMed2000

Human genomics and obesity: finding appropriate drug targets.

The increasing prevalence of obesity worldwide has prompted the World Health Organization (WHO) to classify it as a global epidemic. Around the globe, more than a half billion people are overweight, and the chronic disease of obesity represents a major threat to health care systems in developed and developing countries. The major health hazards associated with obesity are the risks of developing diabetes, cardiovascular disease, stroke, osteoarthritis and some forms of cancer. In this paper, we review the prevalence of obesity and its cost to health care systems and present the relative contribution of environmental conditions and genetic makeup to the development of obesity in people. We also discuss the concept of "essential" obesity in an "obesigenic" environment. Though weight gain results from a sustained imbalance between energy intake and energy expenditure, it is only recently that studies have identified important new mechanisms involved in the regulation of body weight. The etiology of the disease is presented as a feedback model in which afferent signals inform the central controllers in the brain as to the state of the external and internal environment and elicit responses related to the regulation of food intake and energy metabolism. Pharmaceutical agents may intervene at different levels of this feedback model, i.e., reinforce the afferent signals from the periphery, target the central pathways involved in the regulation of food intake and energy expenditure, and increase peripheral energy expenditure and fat oxidation directly. Since obesity results from genetic predisposition, combined with the proactive environmental situation, we discuss new potential targets for generation of drugs that may assist people in gaining control over appetite as well as increasing total energy expenditure and fat oxidation.

Animals↗
PubMed2000

Energy balance and weight regulation: genetics versus environment.

The prevalence of obesity is reaching epidemic proportions in many industrialized countries. There is growing evidence that, even if the trigger of this epidemic is found in changes in the environment, genes are interacting with the environment to cause weight gain. Studies of twins reared apart indicate that approximately two-thirds of the variability in BMI is attributed to genetic factors. From prospective studies in Pima Indians we can ascribe 12% of the variability in BMI to metabolic rate, 5% to fat oxidation, and another probable 10% to the level of spontaneous physical activity. These data indicate that at least 40% of the variability in BMI is related to genetic factors involved in the regulation of food intake and/or volitional activity. This indicates that the most likely successful therapy for obesity may target pathways of the regulation of food intake. Similarly, an environment favouring engagement in physical activity should be promoted.

Body Composition↗
PubMed2000

Low plasma leptin concentration and low rates of fat oxidation in weight-stable post-obese subjects.

OBJECTIVE: A low resting metabolic rate for a given body size and composition, a low rate of fat oxidation, low levels of physical activity, and low plasma leptin concentrations are all risk factors for body weight gain. The aim of the present investigation was to compare resting metabolic rate (RMR), respiratory quotient (RQ), levels of physical activity, and plasma leptin concentrations in eight post-obese adults (2 males and 6 females; 48.9 +/- 12.2 years; body mass index [BMI]: 24.5 +/- 1.0 kg/m2; body fat 33 +/- 5%; mean +/- SD) who lost 27.1 +/- 21.3 kg (16 to 79 kg) and had maintained this weight loss for > or =2 months (2 to 9 months) to eight age- and BMI-matched control never-obese subjects (1 male and 7 females; 49.1 +/- 5.2 years; BMI 24.4 +/- 1.0 kg/m2; body fat 33 +/- 7%). RESEARCH METHODS AND PROCEDURES: Following 3 days of weight maintenance diet (50% carbohydrate and 30% fat), RMR and RQ were measured after a 10-hour fast using indirect calorimetry and plasma leptin concentrations were measured using radioimmunoassay. Levels of physical activity were estimated using an accelerometer over a 48-hour period in free living conditions. RESULTS: After adjustment for fat mass and fat-free mass, post-obese subjects had, compared with controls, similar levels of physical activity (4185 +/- 205 vs. 4295 +/- 204 counts) and similar RMR (1383 +/- 268 vs. 1430 +/- 104 kcal/day) but higher RQ (0.86 +/- 0.04 vs. 0.81 +/- 0.03, p < 0.05). Leptin concentration correlated positively with percent body fat (r = 0.57, p < 0.05) and, after adjusting for fat mass and fat-free mass, was lower in post-obese than in control subjects (4.5 +/- 2.1 vs. 11.6 +/- 7.9 ng/mL, p < 0.05). DISCUSSION: The low fat oxidation and low plasma leptin concentrations observed in post-obese individuals may, in part, explain their propensity to relapse.

Adipose Tissue↗
PubMed2000

Daily energy expenditure in Mexican and USA Pima indians: low physical activity as a possible cause of obesity.

BACKGROUND: Obesity is caused by an imbalance between energy intake and energy expenditure. However, it is unknown whether increased physical activity protects susceptible populations against the development of obesity and type 2 diabetes. OBJECTIVE: To investigate the potential protective role of environment and physical activity against obesity by measuring total energy expenditure in Mexican and USA Pima Indians. METHODS: We compared the physical activity level of 40 (17 female and 23 male; 37+/-11 y, 66+/-13 kg) Mexican Pima Indians from a remote, mountainous area of Northwest Mexico, with 40 age-and-sex matched (17 female and 23 male; 37+/-12 y, 93+/-22 kg) Pima Indians from the Gila River Indian Community in Arizona, USA. We measured total energy expenditure (TEE) by doubly labeled water and calculated physical activity by different methods: physical activity level (PAL) as the ratio of TEE on resting metabolic rate (RMR), TEE adjusted for RMR by linear regression, activity energy expenditure adjusted for body weight (AEE), and activity questionnaire. RESULTS: Physical activity was higher in Mexican Pima Indians when compared with USA Pima Indians as assessed by PAL (1.97+/-0.34 vs 1.57+/-0.16, P<0.0001), TEE adjusted for RMR (3289+/-454 vs 2671+/-454 kcal/day, P<0.0001) and AEE adjusted for body weight (1243+/-415 vs 711+/-415 kcal/day, P<0. 0001). Questionnaires revealed more time spent on occupational activities among Mexican Pima compared with USA Pima (23.9+/-13.3 vs 12.6+/-13.9 h/week, P<0.001). CONCLUSION: These data support a significant role for physical activity in the prevention of obesity in genetically susceptible populations. International Journal of Obesity (2000)24, 55-59

Adult↗
PubMed2000

A polymorphism in the gene encoding CART is not associated with obesity in Pima Indians.

Cocaine- and amphetamine-regulated transcript (CART) is a hypothalamic peptide that may be involved in the regulation of food intake. We screened the human CART gene and identified a novel C-->G substitution in the 3'-untranslated region of exon 3. This polymorphism was genotyped in a total of 68 Pima Indians with extremes of BMI. The frequencies for alleles C and G were 0.76 and 0.24, respectively. There was no evidence of an association between the genotype frequency at this variant and extremes of BMI in this group of Pima Indians. The results of this study do not suggest a significant role for this variant in exon 3 of CART as a determinant of obesity in Pima Indians.

Adult↗
PubMed2000

An autosomal genomic scan for loci linked to plasma leptin concentration in Pima Indians.

OBJECTIVE: To identify chromosomal regions linked to plasma leptin concentrations. DESIGN: Autosomal genome-wide scan, including 516 microsatellite markers. Sib-pair (Haseman-Elston) and variance components methods were used to assess genetic linkage. SUBJECTS: 770 Pima Indians comprising 239 nuclear families (for a total of 1199 sibling-pairs). MEASUREMENTS: Plasma leptin concentrations and body mass index (BMI), adjusted for age and sex. RESULTS: The strongest evidence for linkage with plasma leptin concentration was on chromosome 6p logarithm of odds (LOD) = 2.1 by variance components analysis). There was no evidence for linkage to BMI in this region. Additional regions with marginal evidence for linkage to plasma leptin concentration (LOD > or =1.0) were detected on chromosomes 3, 11, 13, 15 and 16. CONCLUSIONS: The results suggest that a locus on chromosome 6p influences plasma leptin concentrations. Replication studies are needed to exclude the possibility that linkage has been falsely detected.

Adolescent↗
PubMed2000

Novel polymorphisms in the neuropeptide-Y Y5 receptor associated with obesity in Pima Indians.

OBJECTIVE: To investigate whether the neuropeptide Y receptor 5 gene (NPY5R) is associated with obesity in humans. DESIGN: The NPY5R gene was screened for polymorphisms by direct sequencing in two groups of Pima Indians, selected for extremes of body mass index (BMI). Genotype frequencies were analyzed for association with BMI extreme. SUBJECTS: Full-heritage Pima Indians, non-diabetic and not first degree relatives. Obese group: 19 M/24 F, BMI = 49+/-7 kg/m2 (mean+/-s.d.) age = 24+/-2 y, lean group: 16 M/16 F, BMI = 23+/-2 kg/m2, age = 27+/-3 y. MEASUREMENTS: Initially, the entire gene (proximal promoter, exon 1A, coding sequence, 5' and 3' UTRs) was sequenced in a subset of 20 individuals. No variants were found in the coding sequence, however three novel single nucleotide polymorphisms were detected in the non-coding regions: (1) a C-->T transition located within the promoter 28 bp upstream of the exon 1A transcription start site; (2) a T-->C transition 94 bp downstream of the stop codon; and (3) a G-->A transition 432 bp downstream of the stop codon. The polymorphisms were then screened in all 75 subjects. RESULTS: The polymorphisms had mean heterozygosities of 0.34-0.50 and were in strong linkage disequilibrium (P<0.001). Genotype frequencies differed significantly in lean and obese Pimas for P2 (P=0.04) and for a triple haplotype (P=0.02, Bonferroni corrected). CONCLUSION: Considering the importance of this gene in regulation of body weight, the association of these polymorphisms with extremes of BMI in Pima Indians indicates that NPY5R, or a locus nearby, may contribute to susceptibility to obesity in this population.

Adult↗
PubMed2000

De novo lipogenesis in adipose tissue of lean and obese women: application of deuterated water and isotope ratio mass spectrometry.

OBJECTIVE: To evaluate the feasibility of using deuterated water and isotope ratio mass spectrometry to measure de novo fatty acid synthesis in adipose tissue, and to compare this parameter in obese and lean women. SUBJECTS: Six lean and six obese premenopausal Caucasian women in the main study and three obese Pima Indians in a pilot study. MEASUREMENTS: Deuterated water was administered orally twice daily for 14 days to create stable deuterium enrichment in body water, during which series of blood samples were collected to measure body water deuterium enrichment and deuterium incorporation into plasma total Triacylglycerol (TG) fatty acids and total cholesterol. Subcutaneous fat at different sites were sampled at the beginning and the end of deuterium administration to measure deuterium incorporation into TG fatty acids. RESULTS: Fractional de novo synthesis rate of TG fatty acids in adipose tissue was 0. 014+/-0.005 and 0.014+/-0.007% in lean and obese Caucasian women, corresponding to 2+/-0.7 and 5.6+/-3.2 g (P=0.3) of fatty acids synthesized daily, respectively. Plasma TG fatty acids and cholesterol synthesis rates were comparable to those reported previously. A pilot study showed that de novo lipid synthesis in adipose tissue of obese Pima Indians was also quantitatively minor. CONCLUSION: Human adipose tissue, like the liver, does not make a major contribution to whole body lipogenesis under eucaloric conditions. A combination of deuterated water and isotope ratio mass spectrometry is a useful research tool for studying accumulation of de novo synthesized lipids in human adipose tissue.

Adipocytes↗
PubMed2000

The sympathetic nervous system and obesity: role in aetiology and treatment.

The sympathetic nervous system (SNS) is an important component of the autonomic nervous system, and thus plays a major role in the maintenance of homeostasis. The SNS is of particular importance in the control of the cardiovascular system and of a number of metabolic processes. Alterations in SNS effects on metabolism have been implicated in the development and maintenance of obesity, and the SNS is a potential therapeutic target in the treatment of obesity. This review provides an overview of the anatomical and physiological aspects of the SNS, before considering the evidence showing a role for the SNS in the development or treatment of obesity.

Basal Metabolism↗
PubMed2000

Energy metabolism after 2 y of energy restriction: the biosphere 2 experiment.

BACKGROUND: An adaptive decrease in energy expenditure (EE) in response to 6 mo of severely restricted energy intake was shown in a classic semistarvation study-the Minnesota experiment. OBJECTIVE: Our objective was to examine whether such adaptation also occurs in response to less severe but sustained energy restriction. DESIGN: Body composition, 1-wk total EE (TEE), 24-h sedentary EE, and spontaneous physical activity were measured in 8 healthy subjects (4 men and 4 women) at the end of a 2-y confinement inside Biosphere 2. Unexpectedly, the food supply was markedly restricted during most of the confinement and all subjects experienced a marked, sustained weight loss (9.1 +/- 6.6 kg; P: < 0.001) from the low-energy (7000-11000 kJ/d), low-fat (9% of energy), but nutrient-dense, diet they consumed. RESULTS: The TEE inside Biosphere 2, assessed 3 wk before exit, averaged 10700 +/- 560 kJ/d (n = 8). Within 1 wk after exit, the adjusted 24-h EE and spontaneous physical activity were lower in the biospherians (n = 5) than in 152 control subjects (6% and 45%, respectively; both P: < 0.01). Six months after exit and return to an ad libitum diet, body weight had increased to preentry levels; however, adjusted 24-h EE and spontaneous physical activity were still significantly lower than in control subjects. CONCLUSIONS: In lean humans, an adaptive decrease in EE appears to occur not only in states of life-threatening undernutrition, but also in response to less severe energy restriction sustained over several years.

Adult↗
PubMed2000

A comparison of bioimpedance methods for detection of body cell mass change in HIV infection.

The maintenance of body cell mass (BCM) is critical for survival in human immunodeficiency virus (HIV) infection. Accuracy of bioimpedance for measuring change (Delta) in intracellular water (ICW), which defines BCM, is uncertain. To evaluate bioimpedance-estimated DeltaBCM, the ICW of 21 weight-losing HIV patients was measured before and after anabolic steroid therapy by dilution (total body water by deuterium - extracellular water by bromide) and bioimpedance. Multiple-frequency modeling- and dilution-determined DeltaICW did not differ. The DeltaICW was predicted poorly by 50-kHz parallel reactance, 50-kHz impedance, and 200 - 5-kHz impedance. The DeltaICW predicted by 500 - 5-kHz impedance was closer to, but statistically different from, dilution-determined DeltaICW. However, the effect of random error on the measurement of systematic error in the 500 - 5-kHz method was 12-13% of the average measured DeltaICW; this was nearly twice the percent difference between obtained and threshold statistics. Although the 500 - 5-kHz method cannot be fully rejected, these results support the conclusion that only the multiple-frequency modeling approach accurately monitors DeltaBCM in HIV infection.

Adult↗
PubMed2000

Decreased expression of apM1 in omental and subcutaneous adipose tissue of humans with type 2 diabetes.

We have screened a subtracted cDNA library in order to identify differentially expressed genes in omental adipose tissue of human patients with Type 2 diabetes. One clone (#1738) showed a marked reduction in omental adipose tissue from patients with Type 2 diabetes. Sequencing and BLAST analysis revealed clone #1738 was the adipocyte-specific secreted protein gene apM1 (synonyms ACRP30, AdipoQ, GBP28). Consistent with the murine orthologue, apM1 mRNA was expressed in cultured human adipocytes and not in preadipocytes. Using RT-PCR we confirmed that apM1 mRNA levels were significantly reduced in omental adipose tissue of obese patients with Type 2 diabetes compared with lean and obese normoglycemic subjects. Although less pronounced, apM1 mRNA levels were reduced in subcutaneous adipose tissue of Type 2 diabetic patients. Whereas the biological function of apM1 is presently unknown, the tissue specific expression, structural similarities to TNFalpha, and the dysregulated expression observed in obese Type 2 diabetic patients suggest that this factor may play a role in the pathogenesis of insulin resistance and Type 2 diabetes.

Adiponectin↗
PubMed2000

Ethnic differences in insulinemia and sympathetic tone as links between obesity and blood pressure.

Hyperinsulinemia and increased sympathetic nervous system (SNS) activity are thought to be pathophysiological links between obesity and hypertension. In the present study, we examined the relation among heart rate (HR), blood pressure (BP), and percent body fat (hydrodensitometry or DEXA), fasting plasma insulin concentration, and muscle sympathetic nerve activity (MSNA, microneurography) in male, normotensive whites (n=42) and Pima Indians (n=77). Pima Indians have a high prevalence of obesity and hyperinsulinemia but a relatively low prevalence of hypertension. Compared with whites, Pima Indian men had a higher percent body fat (28% versus 21%) and higher fasting insulin concentrations (210 versus 132 pmol/L) but lower MSNA (27 versus 33 bursts/min) (all P<0.001). In both ethnic groups, HR and BP were positively related to percent body fat and MSNA, and both were significant independent determinants of HR and BP in multiple regression analyses. However, MSNA was positively related to percent body fat and the fasting insulin concentration in whites (r=0.60 and r=0.47, both P<0.01) but not in Pima Indians (r=0.15 and r=0.03, NS) (P<0.01 for ethnic differences in the slope of the regression lines). These results confirm the physiological importance of the SNS in normal BP regulation but indicate that the roles of hyperinsulinemia and increased SNS activity as mediators for the relation between obesity and hypertension can differ between different ethnic groups. The lack of an increase in SNS activity with increasing adiposity and insulinemia in Pima Indians may contribute to the low prevalence of hypertension in this population.

Absorptiometry, Photon↗
PubMed2000

Energy expenditure, fat oxidation, and body weight regulation: a study of metabolic adaptation to long-term weight change.

Relatively low rates of energy expenditure and fat oxidation predict body weight gain. Weight gain, in turn, is associated with increases in energy expenditure and fat oxidation that may oppose further weight change. In response to experimental weight gain induced by overfeeding, increases in energy expenditure and fat oxidation are overcompensatory, i.e. greater than predicted for the change in body composition. To determine whether such metabolic adaptation occurs in response to spontaneous long term weight change, we conducted a longitudinal study in which 24-h energy expenditure (24-EE) and 24-h respiratory quotient (24-RQ; i.e. fat to carbohydrate oxidation) were repeatedly measured in 102 Pima Indians at baseline and after a mean follow-up of 3.6 +/- 2.7 yr, during which changes in body weight varied widely (-21 to +28 kg). We found that changes in 24-EE and 24-RQ in response to weight change were related to the amount of weight change, even after adjustment for body composition (partial r = 0.23 and -0.30, respectively; both P < 0.05). For a 15-kg weight gain, the increases in 24-EE (+244 Cal/day) and 24-h fat oxidation (+152 Cal/day) were 33 and 53 Cal/day greater than predicted from the cross-sectional relationship between both measures and body weight. Changes in 24-EE and 24-RQ varied substantially among individuals. Thus, on the average, spontaneous long term weight changes are accompanied by small metabolic adaptations in both energy expenditure and fat oxidation. The metabolic responses to weight changes are highly variable among individuals, however.

Adaptation, Physiological↗