Comparison of body composition, adipocyte size, and glucose and insulin concentrations in Pima Indian and Caucasian children

Pima Indian adults with normal glucose tolerance have higher plasma glucose and insulin concentrations than Caucasian adults. To estimate the age of onset of these differences, and to assess their relationship to abdominal and gluteal adipocyte size, we measured adiposity, adipocyte size, and glucose and insulin concentrations during a glucose tolerance test in lean (less than 20% body fat), prepubertal children from each race. The Pima (n = 13) and Caucasian (n = 10) groups were of similar age, percent body fat, and weight. Pima Indian children had higher fasting glucose (101 +/- 2 v 94 +/- 2 mg/dL, P = .01) and insulin (22 +/- 2 v 15 +/- 2 microU/mL, P less than .01) concentrations and larger abdominal adipocytes (0.49 +/- 0.03 v 0.37 +/- 0.04 microgram lipid/cell, P less than .05) than the Caucasian children. Postprandial glucose and insulin concentrations and gluteal adipocyte size were similar in the two races. The higher plasma glucose and insulin concentrations found in Pima adults are present in lean Pima children, and are associated with increased abdominal adipocyte size. These increases may precede the development of obesity in this racial group.     

Exaggerated pancreatic polypeptide secretion in Pima Indians: can an increased parasympathetic drive to the pancreas contribute to hyperinsulinemia, obesity, and diabetes in humans?

Vagally-mediated hyperinsulinemia is a common abnormality in various rodent models of genetic and hypothalamic obesity that have a high propensity for type 2 diabetes. We hypothesized that Pima Indians, a population with a high prevalence of hyperinsulinemia, obesity, and type 2 diabetes also have an increased parasympathetic drive to the pancreas. To test this, we measured plasma concentrations of insulin and pancreatic polypeptide (PP), a surrogate marker of pancreatic vagal tone, in lean and obese Pima Indian and Caucasian children (n = 43, 26P/17C, 7 +/- 1 y) and adults (n = 92, 61P/31C, 31 +/- 5 y). Pima Indian children had approximately 2-fold higher fasting insulin and 57% higher fasting PP concentrations than age- and sex-matched Caucasian children (P < .05). Although there was no difference in fasting PP concentration between Pima Indian and Caucasian adults, in response to a mixed meal, Pima Indians had a 51% higher early (30 minutes) PP concentration and 2-fold higher early insulin concentration than Caucasians (P < .05). PP concentrations at 60 minutes and 120 minutes after the meal were also markedly higher in both lean and obese Pima Indians compared with lean and obese Caucasians. These results suggest that Pima Indians may have an increased parasympathetic drive to the pancreas, which could lead to a primary hypersecretion of insulin and contribute to their high propensity for obesity and diabetes, as is the case in various rodent models of obesity.     

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     

Low relative resting metabolic rate and body weight gain in adult Caucasian Italians

OBJECTIVE: To investigate the relationship between resting metabolic rate (RMR) and subsequent changes in body size and degree of fatness in a group of adult Caucasian Italians. DESIGN: Prospective, longitudinal, observational study. SUBJECTS: In total, 155 subjects (72 males and 83 females, age range: 18-55 y; BMI: 17.5-63.4 kg/m2) were evaluated. In total, 43 (26 m and 17 f; BMI: 28.9+/-1.1 kg/m2, mean+/-s.e.m.) of them were reassessed 10-12 y later. MEASUREMENTS: Anthropometric and body composition (bioimpedance analysis) parameters and RMR (indirect calorimetry) were taken at baseline and after 10-12 y. RESULTS: Subjects (15 m, 8 f) who gained body weight (arbitrarily defined as a change in body weight > or = 5 kg) had baseline BMI (29.9+/-1.8 vs 28.0+/-1.4; P = NS) and body composition in terms of fat mass (FM%) and fat-free mass (FFM kg) comparable to those of the subjects (11 m, 9 f) whose body weight remained stable. Baseline RMR was significantly lower in subjects who gained weight than in those who did not (108+/-2.1 vs 122+/-3.1 kJ/kg-FFM 24 h; P < 0.001), although it did not differ significantly between the two groups (119+/-2 vs 121+/-2 kJ/kg-FFM 24 h; P = NS) 10-12 y later. Baseline RMR was inversely correlated to both change in body weight (r = -0.57; P < 0.001) and FM (r = -0.50; P < 0.001). CONCLUSION: A low RMR normalized for FFM appears to be associated with body weight gain in the long run in adult Caucasian Italians.     

Resting metabolic rate in obese children before, during and after weight loss.

Resting metabolic rate (RMR) and body composition were measured by indirect calorimetry and body impedance analysis in 14 obese children before weight loss, during weight reduction for 3 weeks with a conventional hypocaloric diet (730 kcal/3050 kJ) and 12 months after weight loss. The initial weight reduction (5.8 +/- 1.2 kg) resulted in a decrease in RMR and fat free mass (FFM) of 17 +/- 10 per cent (P less than 0.001) and 3.1 +/- 2.3 kg (P less than 0.001), respectively. Prior to weight loss (r2 = 0.89, P less than 0.001) and after 12 months follow up (r2 = 0.88, P less than 0.001) RMR correlated positively with FFM. Changes in RMR after 3 weeks weight loss and throughout the follow-up were positively correlated with changes in FFM (r2 = 0.29, P less than 0.05 and r2 = 0.90, P less than 0.001). Our data indicate that RMR in obese children considerably decreased during a 3 weeks weight reduction, but no sustained depression of the metabolic rate after 12 months was found.     

Determinants of energy expenditure and fuel utilization in man: effects of body composition, age, sex, ethnicity and glucose tolerance in 916 subjects.

BACKGROUND: 24-h energy expenditure (24-EE) and 24-h respiratory quotient (24-RQ) are important measurements in obesity research, but their accurate assessment is limited to few specialized laboratories. OBJECTIVES: 1) To provide comprehensive prediction equations for 24-EE, sleeping metabolic rate (SMR) and 24-RQ, based on a large number of Caucasian and Pima Indian subjects, covering a wide range of body weight and composition, body fat distribution, and age and 2) to test whether Pima Indians have lower metabolic rate and/or higher 24-RQ than Caucasians. SUBJECTS AND METHODS: 916 non-diabetic subjects, aged 31.5 +/- 11.9 y, body weight 90.5 +/- 26.1 kg (mean +/- s.d.), (561 males, 355 females; 416 Caucasians, 500 Pima Indians; 720 with normal (NGT) and 196 with impaired (IGT) glucose tolerance) spent 24 h in a respiratory chamber for measurements of 24-EE, SMR and 24-RQ. Fat-free mass (FFM) and fat mass (FM) were assessed by either hydrodensitometry or DEXA. Waist circumference and waist-to-thigh ratio (WTR) were determined as measures of body fat distribution. RESULTS: In a stepwise multiple regression analysis, FFM, FM, sex, age, WTR, and ethnicity were significant independent determinants of 24-EE (2258 +/- 422 kcal/d), explaining 85% of its variability (24-EE (kcal/d)=696 + 18.9 FFM (kg) + 10.O FM (kg) + 180 male -1.9 age (y) + 7.1 WTR (per decimal) + 44 Pima Indian). SMR (1623 +/- 315kcal/d) was determined (78% of variability) by FFM, FM, sex, age, WTR, and glucose tolerance (SMR (kcal/d) = 443 +/- 14.6 FFM (kg) + 6.9 FM (kg) + 79 male - 1.0 age (y) + 5.8 WTR (per decimal) + 38 IGT), but not by ethnicity. Adjustment for the respective variables reduced the variance in 24-EE from 422 to 162 kcal/d and in SMR from 315 to 146kcal/d. 24-RQ (0.854 +/- 0.026) was determined by waist circumference and energy balance (24-RQ = 0.88429-0.00175 waist circumference (cm) + 0.00004 energy balance (%)), but not by sex, ethnicity or glucose tolerance. With this equation only 13% of the variability in 24-RQ could be explained (residual variance 0.024). Compared to Caucasians, Pima Indians had higher 24-EE, but similar SMR and 24-RQ. CONCLUSIONS: This analysis provides comprehensive prediction equations for 24-EE, SMR and 24-RQ from their major known determinants. It confirms the previous findings that, even after adjustment for body composition, age, sex, ethnicity, and glucose tolerance, there is still considerable variability in energy expenditure and substrate oxidation that may, in part, be genetically determined. In adult Pima Indians, we found no evidence for lower metabolic rate or impaired fat oxidation that could explain the propensity towards obesity in this ethnic group.     

Relationship between generalized and upper body obesity to insulin resistance in Asian Indian men.

It has been proposed that excessive insulin resistance in Asian Indians living in urban areas or migrated to western countries is responsible for the higher incidence of type 2 diabetes and coronary heart disease observed in this population. To evaluate whether Asian Indians are more insulin resistant than Caucasians and to define the role of generalized and truncal adiposity, we performed hydrodensitometry, skinfold measurements, and euglycemic-hyperinsulinemic clamps in 21 healthy Asian Indian men and 23 Caucasian men of similar age and body fat content. The glucose disposal rate (Rd) was significantly lower in the Asian Indians than in the Caucasians (3.7+/-1.3 vs. 5.3+/-2.0 mg/min x kg lean body mass, respectively; P = 0.003). Despite similar total body fat content, Asian Indians had higher truncal adiposity than Caucasians (sum of truncal skinfolds, 117+/-37 and 92.4+/-38 mm, respectively). In both Asian Indians and Caucasians, the insulin sensitivity index (Rd/plasma insulin concentrations) was inversely correlated with both total body fat (r = -0.49; P<0.03 and r = -0.67; P<0.001, respectively) and sum of truncal skinfold thickness (r = -0.55; P<0.001 and r = -0.61; P<0.002, respectively). After adjustment for total body fat and truncal skinfold thickness, Asian Indians still had a significantly lower glucose disposal rate (P = 0.04). These results show that Asian Indian men are more insulin resistant than Caucasian men independently of generalized or truncal adiposity. The excessive insulin resistance in Asian Indians is probably a primary metabolic defect and may account for the excessive morbidity and mortality from diabetes and coronary heart disease in this population.     

Resting metabolic rate and postprandial thermogenesis in polycystic ovarian syndrome

To determine whether the high frequency of obesity in women with polycystic ovary syndrome (PCO) is related to a defect in energy expenditure, resting metabolic rate (RMR) and the thermic response to a standard meal were compared in 10 obese PCO women, nine obese but otherwise normal women, and 11 lean women. All groups were matched with respect to age and fat-free mass and the two obese groups were matched for degree of obesity. RMR was measured by indirect calorimetry for 3 h on two days: (1) in the postabsorptive state; and (2) after a 720 kcal (3014 kJ) liquid mixed meal. The thermic effect of food, calculated as 3 h postprandial minus fasting RMR, was significantly greater for the lean [52.9 +/- 5.5 kcal/3 h (221 +/- 23 kJ/3 h)] than the obese [17.2 +/- 5.1 kcal/3 h (72 +/- 21 kJ/3 h)] and the PCO women [22.8 +/- 5.2 kcal/3 h (95 +/- 22 kJ/3)], P less than 0.001). The thermic effect of food was negatively related to percent body fat (r = -0.694, P less than 0.001). Resting metabolic rate did not differ significantly among the three groups, and was strongly related to fat-free mass (r = 0.687, P less than 0.001). These results confirm previous reports of blunted thermogenesis in obese individuals, but provide no evidence of altered resting metabolic rate or postprandial thermogenesis in women with PCO compared with normal women of similar degree of obesity.     

Body weight gain in free-living Pima Indians: effect of energy intake vs expenditure

BACKGROUND: Obesity results from a chronic imbalance between energy intake and energy expenditure. However, experimental evidence of the relative contribution of interindividual differences in energy intake and expenditure (resting or due to physical activity) to weight gain is limited. OBJECTIVE: To assess prospectively the association between baseline measurements of daily energy metabolism and weight changes by studying free-living adult Pima Indians, one of the most obese populations in the world. DESIGN: A study of the pathogenesis of obesity in the Pima Indians living in Southwestern Arizona. The participants were 92 nondiabetic Pima Indians (64M/28F, 35+/-12 y, 35+/-9% body fat; mean+/-s.d.). At baseline, free-living daily energy metabolism was assessed by doubly labeled water and resting metabolic rate (RMR) by indirect calorimetry. Data on changes in body weight (5.8+/-6.5 kg) over a follow-up period of 4+/-3 y were available in 74 (49M/25F) of the 92 subjects. RESULTS: The baseline calculated total energy intake (r=0.25, P=0.028) and RMR (r=-0.28, P=0.016) were significantly associated with changes in body weight. The baseline energy expenditure due to physical activity was not associated with changes in body weight. CONCLUSION: Using state-of-the-art methods to assess energy intake and expenditure in free-living conditions, we show for the first time that the baseline calculated total energy intake is a determinant of changes in body weight in Pima Indians. These data also confirm that a low RMR is a risk factor for weight gain in this population.     

Sex-specific effect of the Val1483Ile polymorphism in the fatty acid synthase gene (FAS) on body mass index and lipid profile in Caucasian children

OBJECTIVE: A Val1483Ile polymorphism in the human fatty acid sythase gene (FAS) has recently been shown to be associated with lower percentage of body fat and substrate oxidation rates in Pima Indians, but its role in other populations has not been described. Here, we investigate the effect of this variant on obesity in Caucasian children and adolescents. SUBJECTS AND METHODS: In total, 738 Caucasian children and adolescents aged 6-17 years of the Leipzig Schoolchildren cohort, which constitutes an unselected representative German population and 205 obese children (body mass index (BMI) 2.71+/-0.04 SDS) were genotyped for genotype-phenotype associations. RESULTS: The frequency of the Ile-allele was lower in German Caucasians compared with Pima Indians (0.03 compared to 0.10). Using generalized linear regression models, there was no effect of the polymorphism on BMI in the whole normal population. However, we identified a significant interaction effect between sex and genotype (P=0.004). Subsequent sex stratified analyses revealed a lower BMI SDS in boys with Ile/Val genotype compared to Val/Val (-0.36+/-0.29 vs 0.09+/-0.05, P<0.05), while an opposite effect was observed in girls (0.48+/-0.19 vs 0.09+/-0.05, P<0.05). In genotype-phenotype associations in obese children, the polymorphism did not affect parameters of insulin, glucose, or lipid metabolism in the whole population. Again, however, obese boys with Ile/Val genotype had significantly higher high-density lipoprotein (HDL) cholesterol levels (1.46+/-0.07 vs 1.23+/-0.03 mmol/l, P<0.05). CONCLUSION: In conclusion, our findings suggest a sex-specific protective effect of the Val1483Ile polymorphism in FAS for obesity in Caucasian boys. In addition, the polymorphism may be associated with a beneficial lipid profile in obese boys.     

Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia

Plasma concentrations of adiponectin, a novel adipose-specific protein with putative antiatherogenic and antiinflammatory effects, were found to be decreased in Japanese individuals with obesity, type 2 diabetes, and cardiovascular disease, conditions commonly associated with insulin resistance and hyperinsulinemia. To further characterize the relationship between adiponectinemia and adiposity, insulin sensitivity, insulinemia, and glucose tolerance, we measured plasma adiponectin concentrations, body composition (dual-energy x-ray absorptiometry), insulin sensitivity (M, hyperinsulinemic clamp), and glucose tolerance (75-g oral glucose tolerance test) in 23 Caucasians and 121 Pima Indians, a population with a high propensity for obesity and type 2 diabetes. Plasma adiponectin concentration was negatively correlated with percent body fat (r = -0.43), waist-to-thigh ratio (r = -0.46), fasting plasma insulin concentration (r = -0.63), and 2-h glucose concentration (r = -0.38), and positively correlated with M (r = 0.59) (all P < 0.001); all relations were evident in both ethnic groups. In a multivariate analysis, fasting plasma insulin concentration, M, and waist-to-thigh ratio, but not percent body fat or 2-h glucose concentration, were significant independent determinates of adiponectinemia, explaining 47% of the variance (r(2) = 0.47). Differences in adiponectinemia between Pima Indians and Caucasians (7.2 +/- 2.6 vs. 10.2 +/- 4.3 microg/ml, P < 0.0001) and between Pima Indians with normal, impaired, and diabetic glucose tolerance (7.5 +/- 2.7, 6.1 +/- 2.0, 5.5 +/- 1.6 microg/ml, P < 0.0001) remained significant after adjustment for adiposity, but not after additional adjustment for M or fasting insulin concentration. These results confirm that obesity and type 2 diabetes are associated with low plasma adiponectin concentrations in different ethnic groups and indicate that the degree of hypoadiponectinemia is more closely related to the degree of insulin resistance and hyperinsulinemia than to the degree of adiposity and glucose intolerance.     

Hypothalamic-pituitary-adrenal axis and sympathetic nervous system activities in Pima Indians and Caucasians

It has been proposed that both hypercortisolism and low sympathetic nervous system (SNS) activity contribute to obesity. Because glucocorticoids inhibit SNS activity, we hypothesized that hypercortisolism and low SNS activity may be found in association in Pima Indians, a population with a high prevalence of obesity. We therefore measured indices of hypothalamic-pituitary-adrenal (HPA) axis and SNS activities in 39 nondiabetic men, 20 Pimas (age, 30+/-5 years; weight, 94+/-26 kg; 35%+/-8% body fat [mean +/- SD]) and 19 Caucasians (33+/-9 years, 91+/-23 kg, 28%+/-11% body fat). HPA axis activity was assessed by measurements of morning fasting plasma corticotropin (ACTH) and cortisol concentrations and 24-hour urinary free cortisol (UFC) excretion. SNS activity was assessed as muscle sympathetic nerve activity (MSNA) by microneurography and by measurement of catecholamines (fasting plasma concentration and 24-hour urinary excretion). Plasma ACTH and cortisol and UFC were similar in Pimas and Caucasians. MSNA was positively correlated with percent body fat (r = .49, P = .002) and was lower in Pimas compared with Caucasians after adjustment for percent body fat (24+/-9 v 31+/-10 bursts/min, P = .04). We conclude that Pima Indians, a population with a high prevalence of obesity, have lower SNS activity but normal HPA axis activity compared with Caucasians.     

Energy need in childhood and adult-onset obese women before and after a nine-month nutrition education and walking program

The effect of a 9-month nutrition education and walking program on total calorie need, resting metabolic rate (RMR), thermic effect of food (TEF), body composition, and activity level was determined in seven women (28-41 years of age) with childhood-onset obesity (CO) and eight women (29-42 years of age) with adult-onset obesity (AO). A 3-week testing period was conducted before and after the 9-month program during which all subjects were fed a controlled, weight-maintaining metabolic diet which was used to determine daily calorie need. Body composition, RMR, and TEF were measured during the second and third weeks of both 3-week testing periods. Body weight decreased significantly for CO (mean -5.7 +/- 9.3 kg) and AO (mean -3.3 +/- 6.2 kg), but fat-free mass (FFM) was unchanged. When comparing pre to post data, mean total calorie need increased by 2.9 percent for CO and 3.1 percent for AO (P greater than 0.05), RMR decreased 3.6 percent for CO and 2.8 percent for AO (P less than 0.05), and TEF increased 11 percent for CO and 50 percent for AO (P less than 0.05). Time spent in light and moderate level activity increased significantly from pre to post. The increase in activity and TEF more than compensated for the slight decrease in RMR (mean -55 kcal/day), contributing to an overall increase in daily energy need (mean = 74 kcal/day) at the end of the program, even for the six women who lost greater than 5 kg body weight.     

The effect of propranolol on free fatty acid mobilization and resting metabolic rate

The role of the sympathetic nervous system in free fatty acid (FFA) mobilization was assessed in this study. FFA turnover rate using 1-14C-palmitic acid and metabolic rate by using indirect calorimetry were measured in ten white and 12 Pima Indian males after an overnight fast and during propranolol infusion (120 micrograms/kg fat-free mass [FFM] bolus and 1.2 micrograms/kg FFM/min). Baseline FFA turnovers were similar in both racial groups and decreased similarly following propranolol infusion (-16% +/- 4%; P less than .001, n = 22). This decrease was greater in more obese subjects (decrease in FFA turnover v % body fat, r = -.59, P less than .01, n = 22). Propranolol also induced an increase in lipid oxidation, which was more marked in the subjects with a high ratio of abdomen to thigh circumference (A/T ratio) (r = .63, P less than .01, n = 22). On average the resting metabolic rate (RMR) was unchanged during propranolol infusion, but individuals with lower A/T ratio had greater decreases in RMR than subjects with higher A/T ratio (r = .48, P less than .05). Assuming that the change in FFA turnover following beta-blockade is proportional to the role that the catecholamines (and therefore the sympathetic nervous system) play in mobilization of FFA, the greater fall in FFA turnover after propranolol infusion in more obese subjects suggests that they have a higher basal sympathetic activity. Furthermore, the lack of decrease in metabolic rate in response to beta-blockade in persons with a high A/T ratio could be the reflection of an even greater SNS activity in individuals with central obesity.     

Bone density and amenorrhea in ballet dancers are related to a decreased resting metabolic rate and lower leptin levels

Osteopenia, which is correlated with amenorrhea and poor nutritional habits, has been well documented in elite ballet dancers. Estrogen replacement therapy and recovery from amenorrhea have not been associated with normalization of bone density. Thus, the osteopenia may be related to changes brought about by chronic dieting or other factors, such as a hypometabolic state induced by poor nutrition. The purpose of this study was to investigate the relationship of chronic dieting and resting metabolic rate (RMR) to amenorrhea and bone density. RMR, bone density, eating disorder assessments, leptin levels, and complete menstrual and medical histories were determined in 21 elite ballet dancers and in 27 nondancers (age, 20-30 yr). No significant correlations were found between high EAT26 scores, a measure of disordered eating, and RMR, bone densities, body weight, body fat, or fat-free mass. However, when RMR was adjusted for fat-free mass (FFM), a significant positive correlation was found between RMR/FFM and bone density in both the arms (P < 0.001) and spine (P < 0.05) in ballet dancers, but not in the normal controls. The dancers also demonstrated significantly higher EAT scores (22.9 +/- 10.3 vs. 4.1 +/- 2.4; P < 0.001) and lower RMR/FFM ratios (30.0 +/- 2.2 vs. 32.05 +/- 2.8; P < 0.01). The only variable to predict lower RMR/FFM in the entire sample was ever having had amenorrhea; this group had significantly higher EAT scores (18.0 +/- 13.5 vs. 10.3 +/- 10.2; P < 0.05), lower leptin levels (4.03 +/- 0.625 vs. 7.10 +/- 4.052; P < 0.05), and lower bone mineral density in the spine (0.984 +/- 0.11 vs. 1.10 +/- 0.13; P < 0.05) and arm (0.773 +/- 0.99 vs. 0.818 +/- 0.01; P < 0.05). We hypothesize that the correlation between low RMR and lower leptin levels and bone density may be more strongly related to nutritional habits in ballet dancers, causing significant depression of RMR, particularly for those with a history of amenorrhea.     

Negative relationship between fasting plasma ghrelin concentrations and ad libitum food intake

Ghrelin is a novel GH secretagogue with orexigenic effects. We hypothesized that high fasting plasma ghrelin concentrations (FxGhr) might predict high ad libitum food intake. FxGhr were measured in 30 normoglycemic subjects: 15 Pima Indians (8 male/7 female; age, 32 +/- 7 yr; body weight, 87 +/- 21 kg; mean +/-sd) and 15 Caucasians (12 male/3 female, 36 +/- 8 yr, 94 +/- 26 kg) in energy balance for 3 d before testing. Subjects then self-selected their food ad libitum for the following 3 d. Mean daily energy intake (DEI) was calculated from the weight of foods consumed and expressed as a percent of weight maintenance energy needs. FxGhr were twice as high in Caucasians as in Pima Indians (103 +/- 53 vs. 52 +/- 18 fmol/ml, P < 0.001) and remained higher after adjustment for age, gender, and body weight (P < 0.0001). Neither DEI, nor percent of weight maintenance energy needs, nor percent of calories from fat differed between the races. In both groups, FxGhr were negatively correlated with DEI (r = -0.61, P = 0.01; r = -0.54, P = 0.04, respectively). These negative relationships were not explained by interindividual differences in age, gender, or body weight. This unexpected finding that low FxGhr predict ad libitum food intake suggests that the role of endogenous ghrelin in the regulation of energy homeostasis remains uncertain.     

Effect of weight loss on resting energy expenditure in obese prepubertal children.

To assess the effect of weight loss on resting metabolic rate (RMR), the energy expenditure of eight obese prepubertal children (age 9 +/- 1 years; weight 48.7 +/- 9.1 kg; BMI 25.3 +/- 3.9) and of 14 age-matched children of normal body weight (age 9 +/- 1 years; weight 28.8 +/- 5.6 kg; BMI 16.5 +/- 1.7) was measured by indirect calorimetry. The obese children were reinvestigated after a mean weight loss of 5.4 +/- 1.2 kg induced by a six-months mixed hypocaloric diet. Before slimming, the obese group showed a higher daily energy intake than the control group (10.40 +/- 3.45 MJ/day vs 7.97 +/- 2.02 MJ/day respectively; P less than 0.05) but a similar value was observed per unit fat-free mass (FFM) (0.315 +/- 0.032 MJ/kgFFM/day vs 0.329 +/- 0.041 MJ/kgFFM/day respectively). The average RMR of the obese children was greater than that of the control group (5217 +/- 531 kJ/day vs 4477 +/- 506 kJ/day) but similar after adjusting for FFM (4728 +/- 3102 kJ/day vs 4899 +/- 3102 kJ/day). Weight loss resulted in a reduction in RMR (5217 +/- 531 kJ/day vs 4874 +/- 820 kJ/day), each kg of weight loss being accompanied by a decrease of RMR of 64 kJ (15.3 kcal) per day. The changes in RMR induced by weight loss paralleled the changes in FFM. No difference was found in average RQ in obese children vs controls (0.85 +/- 0.03 vs 0.87 +/- 0.03 respectively) and in the obese children before and after weight loss (0.87 +/- 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)     

Visfatin concentration in Asian Indians is correlated with high density lipoprotein cholesterol and apolipoprotein A1

BACKGROUND: Visfatin is a recently described adipose tissue derived hormone whose role in humans remains largely unknown. OBJECTIVES: To determine visfatin's relationship to lipoproteins and body composition parameters in Asian Indians and Caucasians. DESIGN: A cross-sectional study. PATIENTS: Men and women living in Montreal, Canada between the ages of 20 and 60 years were recruited for participation in this study. Subjects were excluded if they had a history of CVD or were taking lipid lowering medication. Individuals identified themselves as Asian Indian or Caucasian. MEASUREMENTS: Anthropometric measurements were collected including weight, height, waist circumference, hip circumference and body fat percentage (BF%). Serum samples were analysed for total cholesterol, HDL-C, apoA1, apoB and visfatin. RESULTS: There was no difference in visfatin levels between Indian and Caucasian men (64.50 +/- 3.98 ng/ml vs 73.01 +/- 6.45 ng/ml, ns, respectively) and Indian and Caucasian women (59.03 +/- 5.71 ng/ml vs 77.70 +/- 7.63 ng/ml, ns, respectively), despite large differences in BF%, apoB and the apoB/apoA1 ratio. Visfatin correlated positively to HDL-C and apoA1 in the Indian men (R = 0.42, P = 0.004 and R = 0.48, P = 0.003) and Indian women (R = 0.46, P = 0.05 and R = 0.59, P = 0.01). CONCLUSION: Visfatin concentrations may be related to HDL metabolism in Asian Indian immigrants.     

Sleeping metabolic rate in relation to body mass index and body composition

OBJECTIVES: To determine whether patterns of sleeping metabolic rate (SMR) are altered in obesity. Specifically to determine the relationship between changes in SMR and body weight, body mass index (BMI, kg/m(2)), and fat-free mass (FFM); and to compare resting metabolic rate (RMR) with SMR during different periods of sleep. SUBJECTS: Eighteen healthy, pre-menopausal, obese (BMI >30, n=9) and non-obese (BMI <30, n=9), female subjects (six Caucasians and 12 African-Americans), with an average age of 36 y (range 22-45). MEASUREMENTS: Total energy expenditure (TEE or 24 h EE), metabolic rate (MR), SMR (minimum, average and maximum) and resting metabolic rate (RMR) or resting energy expenditure (REE) measured by human respiratory chamber, and external mechanical work measured by a force platform within the respiratory chamber. Physical activity index (PAL) was derived as TEE/REE. Body composition was determined by dual-energy X-ray absorptiometry (DXA). RESULTS: SMR decreased continuously during sleep and reached its lowest point just before the subject was awakened in the morning by the research staff. Although averages for RMR and SMR were similar, RMR was lower than SMR at the beginning of the sleeping period and higher than SMR in the morning hours. The rate of decrease in SMR was faster with increasing body weight (-0.829, P<0.0001), BMI (correlation factor -0.896, P<0.0001) and FFM (-0.798, P=0.001). The relationship between the slope of SMR decrease and BMI (y=-5 x 10(-6)x(2)+0.0002x-0.0028) is highly significant, with a P-value of <0.0001 and r(2) value of 0.9622. CONCLUSIONS: The rate of decline in metabolic rate during sleep is directly related to body weight, BMI and FFM. Average SMR tends to be lower than RMR in obese subjects and higher than RMR in non-obese subjects.     

Effect of cortisol on muscle sympathetic nerve activity in Pima Indians and Caucasians

The hypothalamo-pituitary-adrenal axis and sympathetic nervous system (SNS) interact to maintain cardiovascular and metabolic homeostasis, especially during stress. Pima Indians have a low SNS activity, which may contribute to both their increased risk of obesity and reduced risk of hypertension. Although glucocorticoids inhibit SNS activity, Pima Indians are not hypercortisolemic compared with Caucasians. This does not exclude the possibility that the SNS is more responsive to an inhibitory effect of cortisol in the former than in the latter group. We measured fasting plasma ACTH and cortisol and muscle SNS activity [muscle sympathetic nervous system activity (MSNA), microneurography] in 58 males [27 Pimas/31 Caucasians]. Seven Pimas and 12 Caucasians were randomized to a double-blind, placebo-controlled, cross-over study to examine the effect of overnight partial chemical adrenalectomy (metyrapone) followed by cortisol replacement (hydrocortisone) on plasma ACTH, cortisol, and MSNA. There were no ethnic differences in fasting plasma ACTH or cortisol, but MSNA adjusted for percent body fat was lower in Pimas than in Caucasians (P < 0.006). No correlation was found between fasting cortisol and basal MSNA. Administration of metyrapone did not lead to significant changes in MSNA. In response to a hydrocortisone infusion, MSNA decreased in Pima Indians (P = 0.03) but not in Caucasians (P = 0.7). Our data indicate that the low SNS activity that predisposes Pima Indians to obesity is not due to a tonic inhibitory effect of cortisol. However, an acute release of cortisol is likely to more effectively contain sympathoexcitation during stress in Pima Indians than in Caucasians, which may be an important mechanism of cardioprotection in this Native American population.