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Biomedical subjects

E Ravussin

Publications and source records attributed to E Ravussin.

At least 91 records · Page 5Linked to original sources
PubMed1997

No effect of the Trp64Arg beta 3-adrenoceptor variant on in vivo lipolysis in subcutaneous adipose tissue.

A Trp64Arg variant in the human beta 3-adrenoceptor is associated with earlier onset of non-insulin-dependent diabetes mellitus and obesity in several populations. The present study investigated in vivo lipolysis in individuals homozygous for the 'variant' allele coding for arginine (Arg) in position 64 of the beta 3-adrenoceptor or homozygous for the 'wild type' tryptophan (Trp) allele. Subjects were 25 healthy, non-diabetic Pima Indians, 8 Arg (2 males, 6 females; aged 34 +/- 9 years, BMI 36.2 +/- 7.7 kg/m2, 43 +/- 11% body fat [mean +/- SD]), and 17 Trp (9 males, 8 females; aged 30 +/- 5 years, BMI 30.4 +/- 6.1 kg/m2, 39 +/- 9% body fat). After an overnight fast, a microdialysis probe was inserted in the subcutaneous adipose tissue and perfused with Ringer's solution. Dialysate was collected in 10-min fractions during a 30-min baseline and during 40 min with isoproterenol, a non-selective beta-adrenergic agonist, added to the perfusate (1 mumol/l). Changes in rate of lipolysis were assessed as changes in dialysate glycerol concentration. The relative changes in dialysate glycerol concentrations in response to isoproterenol, expressed as percent over baseline, were similar in the two groups (i.e. 63 +/- 30 and 74 +/- 28% in the Arg and Trp subjects, respectively). The results were also similar in the two groups after adjustment for sex and percentage of body fat. No differential effect of isoproterenol on blood flow was demonstrated between the two groups (assessed by the ethanol dilution technique). These results are consistent with in vitro studies showing no functional effect of the beta 3-adrenoceptor variant, and/or indicate that the beta 3-adrenoceptor is not very important for subcutaneous adipose tissue lipolysis.

Adipose Tissue↗
PubMed1997

Dietary fat and human obesity.

When energy is in excess, the human body processes nutrients according to an oxidative hierarchy. Excessive carbohydrate and protein intakes are disposed of by increased oxidation. In contrast, excess fat intake does not promote its own oxidation in the short- and mid-term. This leads, in the long-term, to an increase in fat stores. Although increased adiposity represents the common response to increased fat intake, there are interindividual differences in lipid oxidation (probably genetically determined) that may protect from or predispose to obesity.

Body Constitution↗
PubMed1997

Low levels of physical activity in 5-year-old children.

As the prevalence of obesity in Western societies has increased to disturbing levels, interest in the role of physical inactivity in promoting this trend has increased. We assessed physical activity energy expenditure (AEE) in 127 5-year-old children, 43 of whom were white children and 84 Pima Indian children; the latter group represents a population with an extremely high prevalence of obesity. Total energy expenditure (TEE) and resting metabolic rate (RMR) were measured by the doubly labeled water method and indirect calorimetry, respectively. From these measured values, different indexes of physical activity were calculated, including AEE = TEE-(RMR + 0.1 x TEE) and physical activity level (PAL = TEE/RMR). By the age of 5 years, Pima Indian children were significantly heavier (23.0 +/- 5.3 kg vs 19.1 +/- 2.6 kg) and fatter (30 +/- 7% vs 21 +/- 5% body fat) than white children (p < 0.0001), whereas TEE (5996 +/- 1005 kJ/day vs 5690 +/- 760 kJ/day) and RMR (4431 +/- 625 kJ/day vs 4236 +/- 534 kJ/day) were similar in the 2 groups in both absolute values and after adjustment for fat-free mass, fat mass, and sex. Both white and Pima Indian children had physical activity levels 20% to 30% lower (PAL = 1.35 +/- 0.13) than currently recommended by the World Health Organization (1.7 to 2.0). However, the different calculated indexes of physical activity were comparable in the two racial groups. Differences in TEE or AEE are unlikely to explain the obesity seen in Pima Indian children at a later age, suggesting that excess food intake is likely to play a major role in the cause of obesity in this obesity-prone population. However, both white and Pima Indian children have surprisingly low levels of physical activity, a condition that portends poorly for the prevention of obesity in adulthood.

Arizona↗
PubMed1997

Relatively low plasma leptin concentrations precede weight gain in Pima Indians.

Leptin, the product of the ob gene, is a hormone, produced by adipose cells, that inhibits food intake and increases energy expenditure in rodents. In humans, plasma leptin concentrations correlate closely with the size of the adipose tissue depot; however, there is considerable variation in plasma leptin concentrations at any given degree of fatness. To investigate whether individuals prone to weight gain are hypoleptinemic, we measured fasting plasma leptin concentrations in two groups of weight-matched nondiabetic Pima Indians followed for approximately 3 years, 19 of whom subsequently gained weight and 17 of whom maintained their weight. After we adjusted for initial percent body fat, mean plasma leptin concentration was lower in those who gained weight than in those whose weight was stable. These data indicate that relatively low plasma leptin concentrations may play a role in the development of obesity in Pima Indians, a population prone to obesity.

Adult↗
PubMed1997

Acute and prolonged administration of glucocorticoids (methylprednisolone) does not affect plasma leptin concentration in humans.

OBJECTIVE: To investigate the effect of glucocorticoid administration on leptin in humans. DESIGN: A 30 min i.v. infusion of methylprednisolone (METH, 125 mg) or placebo (PLAC) followed by 4 d of oral administration of METH (40 mg/d) or PLAC. Fasting plasma glucose, free-fatty acids (FFA), insulin and leptin concentrations were measured at baseline, 210 min after the beginning of the i.v. infusion and after 4 d of oral treatment. SUBJECTS: Twenty healthy non-diabetic male volunteers (27 +/- 5 y, 72 +/- 9 kg, 20 +/- 7% body fat; means +/- s.d.) fed a weight maintenance diet and randomly assigned to METH (n = 10) or PLAC (n = 10) treatment. RESULTS: At baseline, leptin was positively correlated with % body fat in the 20 subjects (r = 0.53; P < 0.02). Acute METH administration significantly increased fasting plasma glucose (P < 0.01), but had no effect on insulin, FFA or leptin concentrations as compared to PLAC. Prolonged METH administration significantly increased fasting plasma insulin P < 0.05), but had no effect on glucose, FFA or leptin concentrations as compared to PLAC. CONCLUSION: These data suggest that in relatively lean individuals, the administration of therapeutic doses of methylprednisolone does not change plasma leptin concentration.

Administration, Oral↗
PubMed1997

Adiposity, plasma leptin concentration and reproductive function in active and sedentary females.

OBJECTIVE: Circulating leptin has recently been proposed as the peripheral signal indicating the adequacy of nutritional status for reproductive function. To test whether low plasma leptin concentration for a given degree of adiposity is associated with menstrual dysfunction, we measured plasma leptin concentration and body composition in young premenopausal women with normal or abnormal reproductive function. DESIGN: Fasting plasma leptin concentration (ELISA), body composition (dual energy X-ray absorptiometry) and menstrual status (menstrual history and hormonal profile) were assessed in 34 premenopausal women characterized by different levels of physical activity. RESULTS: Body fat content and plasma leptin concentration were both reduced in women with impaired reproductive function (amenorrheic < anovulatory < eumenorrheic women). However, after adjusting plasma leptin concentration for percentage body fat, there was no independent association between leptin and menstrual function. CONCLUSION: Menstrual abnormalities in young premenopausal women seem to occur as a consequence of the linear decline in adiposity and plasma leptin concentration observed in response to inadequate nutritional status. Levels of adiposity below 15% and plasma leptin concentration below 3 ng/ml are more likely to be associated with impaired reproductive function.

Adipose Tissue↗
PubMed1997

Relationship of the white blood cell count to body fat: role of leptin.

The white blood cell (WBC) count is correlated to the amount of body fat in humans, but the mechanism for this association is unknown. Leptin, a 16 kD protein produced in adipocytes, circulates in humans in direct proportion to the amount and percentage of body fat. Recent evidence suggests that leptin and the leptin receptor are part of a novel pathway which stimulates haemopoiesis. This study was designed to test whether fasting plasma leptin concentrations contribute to the relationship between the WBC count and body fat. 117 Pima Indians with a wide range in body composition were studied. The WBC count was positively correlated with percentage of body fat (r = 0.44, P = 0.0001) and fasting plasma leptin concentration (r = 0.38, P = 0.0001). In multiple regression analyses, age, gender and percent body fat were significant independent determinants of the WBC count. After controlling for age and gender, percent body fat accounted for 23% of the variance in the WBC count (partial r = 0.48, P = 0.0001). In similar models which also included plasma leptin concentration, percent body fat remained significantly related to the WBC count. but only accounted for 7% of its variance (partial r = 0.27, P = 0.003). Based on these results, and the demonstration that leptin directly effects the stimulation of proliferation of haemopoietic stem cells in vitro, we hypothesize that the relation of the WBC count to percent body fat may be mediated, in part, through the effect of leptin.

Adipose Tissue↗
PubMed1997

Ad libitum food intake in humans after manipulation of glycogen stores.

It is controversial whether food intake in humans is under day-to-day regulation to maintain constant body glycogen stores. In eight white males with a mean (+/-SD) age of 30 +/- 4 y, body weight of 82 +/- 20 kg, and percentage body fat of 22 +/- 5%, exercise and diets were used to produce either high (HG) or low glycogen (LG) stores in a randomized crossover design. After each treatment a vastus lateralis muscle biopsy was obtained. Subsequent ad libitum food intake was measured with an automated food-selection system during 2 d in a respiratory chamber. Despite a 46 +/- 21% difference in muscle glycogen between the two treatments, ad libitum 2-d food intakes (energy, weight, or macronutrients) were similar between treatments (HG: 23.80 +/- 4.67 MJ/d; LG: 21.20 +/- 6.73 MJ/d). However, energy intake on the second day of ad libitum feeding was negatively correlated with carbohydrate balance on the first day, adjusted for the effect of total energy intake and treatment. Adjusted carbohydrate balance on day 1 only explained 9% of the variance in energy intake on day 2. The 24-h respiratory quotient on the first day after treatment was higher after the HG than after the LG treatment: 0.94 +/- 0.04 and 0.88 +/- 0.07 (P < 0.001). The findings suggest that 1) body glycogen stores play at most a minor role in short-term food intake regulation, and 2) in the short term, imbalances in glycogen stores are corrected by adjustments of macronutrient oxidation rates.

Adult↗
PubMed1997

Structure and sequence variation at the human leptin receptor gene in lean and obese Pima Indians.

The cloning of human and mouse cDNAs from brain that encode high affinity leptin receptors was recently reported. We have physically localized the human leptin receptor gene (LEPR) to a region at 1p31, between the anonymous microsatellite markers D1S515 and D1S198. The genomic structure of the human leptin receptor gene, corresponding to the published human brain cDNA sequence, spans over 70 kb and includes 20 exons. Since the leptin receptor gene is a candidate gene for obesity, and because of its proximity to D1S198, a marker previously linked to insulin secretion, the LEPR gene was sequenced in 20 non-diabetic Pima Indians chosen for extremes in percent body fat and in their acute insulin response to intravenous glucose. Seven polymorphic sites were identified. Two of these polymorphisms, Lys109Arg and Gln223Arg, are amino acid substitutions in the extracellular domain of the leptin receptor, one polymorphism is a silent substitution, and four occur in non-coding regions of the leptin receptor. Four of these sites are in linkage disequilibrium with one another. Nucleotides at three noncoding polymorphic sites were found exclusively in obese Pima Indians. This demonstrates an association between variation at the leptin receptor gene and obesity in humans.

Adipose Tissue↗
PubMed1997

Plasma leptin responses to fasting in Pima Indians.

Leptin is believed to play a role in the regulation of energy balance, but little is known about factors influencing plasma leptin concentrations. To determine the effect of short-term changes in energy balance, we measured plasma leptin concentrations as well as plasma glucose, insulin, triglyceride, nonesterified fatty acid concentrations, and metabolic rate in response to a standard test meal followed by a 24-h fast in 21 healthy Pima Indians. Plasma leptin concentrations decreased by 8% (P < 0.05) 2-4 h after the test meal. They returned to baseline 6-12 h after the subjects ate, then subsequently decreased, and, by the end of the fast, were an average of 37% below baseline (P < 0.0001). Changes in plasma leptin concentrations did not correlate with changes in plasma glucose, insulin, triglyceride, or nonesterified fatty acid concentrations or with changes in metabolic rate. The results of this study indicate that plasma leptin concentrations decrease in response to short-term energy restriction. These changes were not due to changes in glucose, insulin, triglycerides, or nonesterified fatty acids, nor did they relate to changes in metabolic rate. The decrease in plasma leptin concentrations with fasting may be an important homeostatic response to an energy deficit, stimulating food intake and thus restoring energy balance.

Adipose Tissue↗
PubMed1997

Fasting hyperinsulinemia is a predictor of increased body weight gain and obesity in Pima Indian children.

Hyperinsulinemia is commonly associated with obesity, but it has not been determined which defect comes first. Some have proposed that hyperinsulinemia may precede obesity in populations prone to NIDDM, such as Pima Indians or Pacific Islanders. In contrast, longitudinal studies in adults show that insulin sensitivity and low fasting insulin concentrations are associated with increased weight gain, whereas insulin resistance seems to protect against weight gain. The present study examined whether fasting plasma hyperinsulinemia is a risk factor for weight gain in prepubertal children in the Pima Indian population-a population that is prone to obesity. Fasting plasma insulin concentration was measured in 328 5- to 9-year-old Pima Indian children (147 boys and 181 girls) with normal glucose tolerance. Follow-up weight was obtained an average of 9.3 +/- 1.9 years (means +/- SD) later at age 15-19 years. Fasting plasma insulin concentration correlated with the rate of weight gain per year in both boys (r = 0.42; P < 0.0001) and girls (r = 0.20; P < 0.01) and was associated with the rate of weight gain, independent of known determinants of weight change, i.e., initial relative weight, change in height, age, and sex. Similar relationships were found between fasting plasma insulin concentration and the change in relative weight and in triceps skinfold thickness-two indicators of obesity. In conclusion, fasting hyperinsulinemia may be a risk factor for the development of obesity in young children.

Arizona↗
PubMed1997

Genomewide search for genes influencing percent body fat in Pima Indians: suggestive linkage at chromosome 11q21-q22. Pima Diabetes Gene Group.

On the basis of accumulating evidence that obesity has a substantial genetic component, a genomewide search for linkages of DNA markers to percent body fat is ongoing in Pima Indians, a population with a very high prevalence of obesity. An initial screen of the genome (>600 markers in 874 individuals) has been completed using highly polymorphic markers (mean heterozygosity = .67). Reported here are the sib-pair linkage results for percent body fat (277 siblings), the best available indicator of overall obesity. Single-marker linkages to percent body fat were evaluated by sib-pair analysis for quantitative traits. From these analyses, the best evidence of genes influencing body fat came from markers at chromosome 11q21-q22 and 3p24.2-p22 (P = .001; LOD = 2.0). Regions flanking these markers were further investigated by multipoint linkage. The evidence for linkage at 11q21-q22 increased to P = .0002 (LOD = 2.8), peaking between markers D11S2000 and D11S2366. Evidence for linkage at 3p24.2-p22 did not change. No association was detected for any marker in the region. Although several genes are known in the 11q21-q22 region, none have been implicated as candidate genes for obesity.

Adipose Tissue↗
PubMed1997

Familiality of physical and metabolic characteristics that predict the development of non-insulin-dependent diabetes mellitus in Pima Indians.

Susceptibility to non-insulin-dependent diabetes mellitus (NIDDM) is largely genetically determined. In Pima Indians, obesity, insulin resistance, and a low acute insulin response (AIR) to an intravenous glucose infusion are each predictors of the disease. To ascertain whether these phenotypes are genetically determined, we estimated their familiality in nondiabetic Pima Indians with a maximum-likelihood method. Percentage body fat (PFAT) was highly familial (h2 =.76), whereas waist/ thigh circumference ratio (W/T ratio) was not significantly familial after controlling for PFAT (h2 = .16). AIR was also highly familial (h2 = .80 at 10 min), even after controlling for PFAT and insulin action (h2 = .70). Insulin action at physiologic plasma insulin concentrations was familial (h2 = .61) but less so after controlling for PFAT and W/T ratio (h2 = .38). At maximally stimulating insulin concentrations, insulin action was familial (h2 = .45) and was less influenced by controlling for PFAT and W/T ratio (h2 = .49). We conclude that in Pima Indians (1) PFAT and AIR are highly familial traits, (2) central distribution of fat is not a familial trait when controlled for PFAT, (3) 38%-49% of the variance in insulin action, independent of the effect of obesity, is familial, and (4) PFAT, AIR, and insulin action are useful traits to study genetic susceptibility to NIDDM. Because genetic parameter estimates are applicable only to the populations from which they were estimated, it is important to determine whether these estimates of familialities in Pima Indians can be confirmed in other populations before the utility of these traits in searching for NIDDM susceptibility genes in those populations can be fully advocated.

Adipose Tissue↗
PubMed1996

Lack of relationship between muscle sympathetic nerve activity and skeletal muscle vasodilation in response to insulin infusion.

Increases in plasma insulin concentration result in vasodilation in skeletal muscle but also in an increase in muscle sympathetic nerve activity (MSNA) which is thought to cause vasoconstriction. The increase in MSNA could therefore be a response to vasodilation (baroreflex), or MSNA could cause vasodilation via putative sympathetic vasodilatory fibres. To examine the relationship between vasodilation, MSNA and insulin action we studied nine non-diabetic Pima Indian men (age 29 +/- 7 years, weight 91 +/- 19 kg, 29 +/- 6% body fat, mean +/- SD) during sequential euglycaemic clamps at low and high insulin doses (80 and 600 mU.m-2.min-1). Leg blood flow was measured by thermodilution, leg glucose uptake by the balance technique, arterial pressure by invasive monitoring and MSNA by microneurography of the peroneal nerve. Whole body glucose uptake (M) ranged from 6.7 to 48.3 during low dose and from 9.4 to 67.7 mumol kg fat free mass-1.min-1 during high dose insulin infusion. At both insulin doses, incremental leg blood flow correlated with M (r = 0.63 and 0.71, respectively). No correlation was found between incremental MSNA and leg blood flow, M or leg glucose uptake. Blood pressure was unchanged throughout the study. MSNA increased after 15-40 min of insulin infusion in all the subjects, whereas leg blood flow started to increase only after 45 min in the most insulin sensitive but not in the most insulin resistant subjects. Thus, insulin stimulates MSNA more rapidly than vasodilation. In conclusion, insulin-mediated MSNA: 1) is neither a response to nor a cause of the vasodilation observed in insulin sensitive men, 2) has no net pressor effect even in the most insulin resistant men in whom insulin-mediated vasodilation was impaired. We conclude that the effect of insulin to stimulate MSNA is dissociated from its acute haemodynamic action.

Adult↗
PubMed1996

Role of lipids in development of noninsulin-dependent diabetes mellitus: lessons learned from Pima Indians.

We studied the role of lipids in the pathogenesis of noninsulin-dependent diabetes mellitus (NIDDM) in Pima Indians. High plasma levels of nonesterified fatty acid (NEFA) predicted development of NIDDM, but this effect cannot entirely be explained by the glucose-fatty acid cycle. Dyslipidemia, although often associated with diabetes, did not seem to predict NIDDM and might rather be associated with, or the consequence of insulin resistance. In some individuals, a single amino acid substitution in the intestinal fatty acid binding protein could result in increased rates of intestinal absorption of dietary NEFA and thereby contribute to increased lipid-oxidation rates and insulin resistance.

Arizona↗
PubMed1996

Decreased ratio of fat to carbohydrate oxidation with increasing age in Pima Indians.

BACKGROUND: Some metabolic changes related to age may increase the prevalence of obesity. Previous studies have shown that a low relative metabolic rate and a low ratio of fat to carbohydrate utilization are predictors of body weight gain. However, a possible relationship between age and energy substrate utilization (respiratory quotient; RQ = VCO2/VO2) has not been reported. OBJECTIVE: To determine whether RQ increases and therefore fat oxidation decreases with age in Pima Indian men, independent of body fat and energy balance. METHODS: We analyzed longitudinal data collected in seven non-diabetic Pima Indian men (31 +/- 6 years, 167 +/- 8 cm, 111.0 +/- 23.7 kg and 41 +/- 9% fat at baseline) who had repeated measurements of 24-hour RQ 7 years apart. On both admissions, subjects were fed a weight maintenance diet (50% carbohydrate, 30% fat and 20% protein) for 3 days before spending 1 day within a respiratory chamber for measurements of 24-hour energy expenditure, basal metabolic rate, sleeping metabolic rate and 24-hour RQ. Paired t-test was used to determine differences between the first and last measurement of 24-hour RQ. Cross-sectional data in 131 Pima Indian men (28 +/- 9 years, 171 +/- 6 cm, 94.5 +/- 24.4 kg, and 32 +/- 9% fat) were also analyzed to determine the relationship between 24-hour RQ and age. Multiple regression analysis was used to adjust 24-hour RQ for differences in energy balance (intake/expenditure in %) and percent body fat and metabolic rate for differences in body size and composition. RESULTS: Over a 7-year period, mean unadjusted and adjusted 24-hour RQ increased (p < 0.01). Cross-sectional data analysis showed that both the unadjusted (r = 0.19, p < 0.03) and adjusted (r = 0.19, p < 0.03) 24-hour RQ correlated with increasing age while adjusted BMR (r = -0.21, p < 0.02) correlated inversely with age. CONCLUSIONS: Despite a higher body fat content, older individuals utilize less fat than their younger counterparts. Reduced fat utilization and decreased BMR with age may both contribute to increasing obesity in older individuals.

Adult↗