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Biomedical subjects

P Antonio Tataranni

Publications and source records attributed to P Antonio Tataranni.

At least 19 recordsLinked to original sources
PubMed2006

11beta-hydroxysteroid dehydrogenase type 1 in adipose tissue and prospective changes in body weight and insulin resistance.

OBJECTIVE: Increased mRNA and activity levels of 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1) in human adipose tissue (AT) are associated with obesity and insulin resistance. The aim of our study was to investigate whether 11betaHSD1 expression or activity in abdominal subcutaneous AT of non-diabetic subjects are associated with subsequent changes in body weight and insulin resistance [homeostasis model assessment of insulin resistance (HOMA-IR)]. RESEARCH METHODS AND PROCEDURES: Prospective analyses were performed in 20 subjects (two whites and 18 Pima Indians) who had baseline measurements of 11betaHSD1 mRNA and activity in whole AT (follow-up, 0.3 to 4.9 years) and in 47 Pima Indians who had baseline assessments of 11betaHSD1 mRNA in isolated adipocytes (follow-up, 0.8 to 5.3 years). RESULTS: In whole AT, although 11betaHSD1 mRNA levels showed positive associations with changes in weight and HOMA-IR, 11betaHSD1 activity was associated with changes in HOMA-IR but not in body weight. 11betaHSD1 mRNA levels in isolated adipocytes were not associated with follow-up changes in any of the anthropometric or metabolic variables. DISCUSSION: Our results indicate that increased expression of 11betaHSD1 in subcutaneous abdominal AT may contribute to risk of worsening obesity and insulin resistance. This prospective relationship does not seem to be mediated by increased 11betaHSD1 expression in adipocytes.

11-beta-Hydroxysteroid Dehydrogenase Type 1↗
PubMed2006

Physiological evidence for the involvement of peptide YY in the regulation of energy homeostasis in humans.

OBJECTIVE: To explore the potential role of the endogenous peptide YY (PYY) in the long-term regulation of body weight and energy homeostasis. RESEARCH METHODS AND PROCEDURES: Fasting and postprandial plasma PYY concentrations were measured after an overnight fast and 30 to 180 minutes after a standardized meal in 29 (21 men/8 women) non-diabetic subjects, 16 of whom had a follow-up visit 10.8 +/- 1.4 months later. Ratings of hunger and satiety were collected using visual analog scales. Resting metabolic rate (RMR) (15-hour RMR) and respiratory quotient (RQ) were assessed using a respiratory chamber. RESULTS: Fasting PYY concentrations were negatively correlated with various markers of adiposity and negatively associated with 15-hour RMR (r = -0.46, p = 0.01). Postprandial changes in PYY (area under the curve) were positively associated with postprandial changes in ratings of satiety (r = 0.47, p = 0.01). The maximal PYY concentrations achieved after the meal (peak PYY) were negatively associated with 24-hour RQ (r = -0.41, p = 0.03). Prospectively, the peak PYY concentrations were negatively associated with changes in body weight (r = -0.58, p = 0.01). DISCUSSION: Our data indicate that the endogenous PYY may be involved in the long-term regulation of body weight. It seems that this long-term effect was not exclusively driven by the modulation of food intake but also by the control of energy expenditure and lipid metabolism.

Adolescent↗
PubMed2006

Gestational glucose tolerance and risk of type 2 diabetes in young Pima Indian offspring.

The in utero environment is a powerful risk factor for type 2 diabetes in offspring, but little is known about the risk conveyed by nondiabetic gestational glucose levels. This issue was explored in 911 nondiabetic Pima Indian mothers and 1,436 of their children. Associations were assessed in multivariate models between maternal third trimester glucose tolerance and indexes of body composition and glycemic control in their children. At parturition, the mothers' ages ranged from 14 to 43 years. Offspring were studied at age 0-39 years. An SD (1.3 mmol/l) of maternal glucose was associated with 56 g higher birth weight (P = 0.0002). This effect persisted when only offspring of normal glucose tolerant mothers were examined (57 g, P < 0.0001). In Cox proportional hazards models, the adjusted hazard rate ratio for offspring risk of diabetes per SD maternal glucose was 1.6 (95% CI 1.3-2.0, P < 0.0001). When only offspring of normal glucose tolerant mothers were examined, the risk was reduced but remained significant (1.3 [1.04-1.71], P = 0.026). In conclusion, maternal glycemia during pregnancy is associated with increased birth weight and risk of diabetes in Pima Indian offspring, even when mothers are normal glucose tolerant during pregnancy. Thus, prevention of offspring type 2 diabetes may require strategies that focus on improving gestational glucose tolerance even within the normal range.

Adolescent↗
PubMed2005

In pursuit of neural risk factors for weight gain in humans.

Obesity is a multifactorial disease associated with an increased risk of type 2 diabetes, coronary artery disease, cancer, and consequently, with a reduced length of life. Metabolic phenotypes of reduced energy expenditure have been associated with weight gain, but their contribution has been estimated to be relatively small. On the other hand, excessive food intake is likely to be the major determinant of positive energy balances and it is underlied by both non-conscious (homeostatic) and conscious (perceptual, emotional, and cognitive) phenomena processed in the brain. Functional neuroimaging is a promising tool to investigate these neural substrates in humans, because it provides a measurement of state-dependent brain regional activity, bridging the gap between neural events and behavioral responses. Using this technology, a few studies have provided the first evidence of functional differences between obese and lean individuals in the brain's response to energy intake and investigated the presence of neural risk factors of weight gain.

Animals↗
PubMed2005

Intrauterine exposure to diabetes is a determinant of hemoglobin A(1)c and systolic blood pressure in pima Indian children.

CONTEXT/OBJECTIVE: Given the increasing rates of both childhood obesity and type 2 diabetes (T2DM), we investigated whether maternal diabetes status during pregnancy is a determinant of risk factors associated with T2DM or cardiovascular disease in offspring during childhood. DESIGN/PARTICIPANTS: Forty-two Pima Indians, aged 7-11 yr, were identified retrospectively from maternal oral glucose tolerance tests as offspring of a diabetic pregnancy (22 ODM, eight males, 14 females) or offspring born before the mother developed diabetes (20 PRE, 12 males, eight females). SETTING/MAIN OUTCOME MEASURES: Weight, height, body mass index, percent body fat, blood pressure, and fasting concentrations of glucose, insulin, hemoglobin A1c (HbA1c), total cholesterol, triglycerides, and high-density lipoprotein-cholesterol were measured while staying in an in-patient clinical research unit and compared in cross-sectional analyses. RESULTS: After adjustment for age and gender, ODM had significantly higher concentrations of HbA1c (ODM = 5.7 +/- 0.4, PRE = 5.0 +/- 0.4%, P = 0.002), higher systolic (SBP) blood pressure (ODM = 118 +/- 13, PRE = 107 +/- 10 mm Hg; P = 0.02), and lower concentrations of high-density lipoprotein (ODM = 41 +/- 9, PRE = 48 +/- 6 mg/dl, P = 0.03) than PRE. Maternal diabetes status during pregnancy persisted as a significant determinant of SBP (beta = 7.50, P = 0.03) and HbA1c (beta = 0.43, P = 0.002), independent of age, gender, and percent body fat. CONCLUSION: Intrauterine exposure to diabetes is a significant determinant of higher SBP and HbA1c during childhood, independent of adiposity and a genetic predisposition to T2DM. These data suggest that in utero exposure to diabetes confers an additional independent risk for the development of T2DM and/or cardiovascular disease later in life.

Arizona↗
PubMed2005

Sensory experience of food and obesity: a positron emission tomography study of the brain regions affected by tasting a liquid meal after a prolonged fast.

The sensory experience of food is a primary reinforcer of eating and overeating plays a major role in the development of human obesity. However, whether the sensory experience of a forthcoming meal and the associated physiological phenomena (cephalic phase response, expectation of reward), which prepare the organism for the ingestion of food play a role in the regulation of energy intake and contribute to the development of obesity remains largely unresolved. We used positron emission tomography (PET) and 15O-water to measure changes in regional cerebral blood flow (rCBF) and to assess the brain's response to the oral administration of 2 ml of a liquid meal (Ensure Plus, 1.5 kcal/ml) after a 36-h fast and shortly before consuming the same meal. Twenty-one obese (BMI > 35 kg/m2, 10M/11F, age 28 +/- 6 years, body fat 40 +/- 6%) and 20 lean individuals (BMI < 25 kg/m2, 10M/10F, age 33 +/- 9 years, body fat 21 +/- 7%) were studied. Compared to lean individuals, obese individuals had higher fasting plasma glucose (83.3 +/- 6.2 vs. 75.5 +/- 9.6 mg/dl; P = 0.0003) and insulin concentrations (6.1 +/- 3.5 vs. 2.5 +/- 1.7 microU/ml; P < 0.0001) and were characterized by a higher score of dietary disinhibition (i.e., the susceptibility of eating behavior to emotional factors and sensory cues, 5.7 +/- 3.6 vs. 3.5 +/- 2.7; P = 0.01) assessed by the Three Factor Eating Questionnaire. In response to the sensory experience of food, differences in rCBF were observed in several regions of the brain, including greater increases in the middle-dorsal insula and midbrain, and greater decreases in the posterior cingulate, temporal, and orbitofrontal cortices in obese compared to lean individuals (P < 0.05, after small volume correction). In a multiple regression model, percentage of body fat (P = 0.04), glycemia (P = 0.01), and disinhibition (P = 0.07) were independent correlates of the neural response to the sensory experience of the meal in the middle-dorsal insular cortex (R2 = 0.45). We conclude that obesity is associated with an abnormal brain response to the sensory aspects of a liquid meal after a prolonged fast especially in areas of the primary gustatory cortex. This is only partially explained by the elevated glycemia and high level of disinhibition which characterize individuals with increased adiposity. These results provide a new perspective on the understanding of the neuroanatomical correlates of abnormal eating behavior and their relationship with obesity in humans.

Adipose Tissue↗
PubMed2005

Lack of relationship between calcium intake and body size in an obesity-prone population.

OBJECTIVE: Dietary calcium intake, especially from dairy products, may have a protective effect against obesity. This study aimed to determine if calcium intake is associated with body weight and adiposity in Pima Indians, an obesity-prone population. RESEARCH METHODS AND PROCEDURES: Subjects were 65 Pima Indian adults (35 men/30 women, age 33+/-8 years [mean+/-standard deviation]) participating in a study of eating behavior and 78 Pima Indian children (36 boys/42 girls, age 10.4+/-0.3 years) participating in a study of childhood obesity. Height and weight were measured, and body composition was determined by dual-energy x-ray absorptiometry. Food intake in adults was assessed using the Block 1998 Food Questionnaire; food intake in children was assessed using a 24-hour recall with parental assistance. RESULTS: In adults, mean energy intake was 3,163+/-1,037 kcal/day, mean percentage of energy from fat was 41%+/-7%, and calcium intake was 914+/-333 mg/day. In children, mean energy intake was 1,988+/-733 kcal/day, mean percentage of energy from fat was 36%+/-9%, and calcium intake was 637+/-352 mg/day, half the recommended daily intake for this age group. There were no significant associations between calcium intake and body weight (r=0.05, P=.71; r=0.04, P=.73), body fat (r=0.16, P=.19; r=0.12, P=.42), or body mass index (r=0.01, P=.97; r=0.04, P=.77) in either adults or children, respectively. DISCUSSION: One explanation for the lack of association between reported calcium intake and body size in Pima Indians may be that the high-fat, high-energy diet consumed by the population overwhelmed the "anti-obesigenic" effect of calcium. CONCLUSIONS: We were unable to find an association between calcium intake and body size or adiposity in Pima Indian adults and children. Although the essentiality of calcium to bone health is well established, the role of calcium and dairy product intake in obesity and weight management remains uncertain.

Absorptiometry, Photon↗
PubMed2005

Habitual physical activity in children: the role of genes and the environment.

BACKGROUND: Understanding the factors that contribute to physical inactivity in children is important because sedentary behavior strongly relates to metabolic disorders such as obesity and diabetes. OBJECTIVE: We aimed to quantify the genetic and environmental influences on physical activity energy expenditure (PAEE) in 100 sex-concordant dizygotic (n = 38) and monozygotic (n = 62) twin pairs aged 4-10 y. DESIGN: Resting metabolic rate (RMR) was assessed by using respiratory gas exchange, total energy expenditure (TEE) by using doubly labeled water, and body composition by using dual-energy X-ray absorptiometry. Structural equation modeling was used to partition the phenotypic variance into additive genetic (a2) and common (c2) and unshared (e2) environmental components. RESULTS: Because PAEE [TEE - (RMR + 0.1 x TEE)] depends on body weight, which is highly heritable, we tested several models: 1) after adjustment for age, sex, ethnicity, study date, season, and weight, a2 explained none of the phenotypic variance in PAEE (95% CI: 0%, 38%), whereas c2 and e2 accounted for 69% (33%, 77%; P = 0.001) and 31% (23%, 39%; P < 0.001) of the variance, respectively; 2) after adjustment for the cofactors in model 1, a2 explained 19% of the phenotypic variance in TEE (0%, 60%; P = 0.13), whereas c2 and e2 accounted for 59% (16%, 79%; P = 0.007) and 23% (17%, 31%; P < 0.0001) of the variance, respectively; 3) in models adjusted as above (excluding weight), a2 explained no variance in physical activity level (TEE/RMR) (0%, 32%; P = 0.50), whereas c2 and e2 explained 65% (34%, 60%; P = 0.001) and 35% (28%, 45%; P < 0.0001) of the variance, respectively. CONCLUSIONS: Our data suggest that the familial resemblance in physical activity in these children is explained predominantly by shared environmental factors and not by genetic variability.

Absorptiometry, Photon↗
PubMed2005

Variations in peptide YY and Y2 receptor genes are associated with severe obesity in Pima Indian men.

Peptide YY (PYY) and Y2 receptor (Y2R) may be important in the central regulation of body weight and food intake. To determine whether genetic variation in PYY and/or Y2R may contribute to morbid obesity in humans, these genes were sequenced in 83 extremely obese Pima Indians (BMI > or = 50 kg/m2). Sequencing of PYY identified three single nucleotide polymorphisms (SNPs) in the untranslated region. Sequencing of the Y2R coding region identified one missense (Ala172Thr) substitution and two silent substitutions. Eight additional SNPs in the 5' untranslated region of Y2R were identified from public databases. These SNPs were genotyped in 489 full-heritage adult Pimas (362 severely obese and 127 nondiabetic, nonobese subjects), who are not first-degree relatives, for association analysis. The PYY variants were not associated with obesity, whereas four variants from two haplotype blocks in Y2R were marginally associated (P = 0.054-0.067) with obesity. However, if the analysis was restricted to men (n = 167, 100 obese and 67 lean), the PYY variants and two SNPs in Y2R that were in complete linkage disequilibrium were significantly associated with severe obesity (P = 0.001 and P = 0.002, respectively). Our data suggest that the PYY-Y2R pathway may influence body weight through a sex-specific mechanism, but this finding requires confirmation in other populations.

5' Untranslated Regions↗
PubMed2004

Interaction between an 11betaHSD1 gene variant and birth era modifies the risk of hypertension in Pima Indians.

11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1) is a candidate gene for hypertension, diabetes, and obesity through altered glucocorticoid production. This study explored the association of 11betaHSD1 gene variants with diabetes, hypertension, and obesity in a longitudinal population study of American Indians (N=918; exams=5508). In multivariate mixed models assuming an additive effect of genotype, a 5' upstream variant (rs846910) was associated with blood pressure (diastolic blood pressure beta=1.58 mm Hg per copy of the A allele, P=0.0008; systolic blood pressure beta=2.28 mm Hg per copy of the A allele, P=0.004; mean arterial blood pressure beta=1.83 mm Hg per copy of the A allele, P=0.0006) and hypertension (odds ratio=1.27 per copy of the A allele, P=0.02). However, birth date modified these associations (test for interaction: diastolic blood pressure P=0.16; systolic blood pressure P=0.007; mean arterial blood pressure P=0.01), such that the magnitude and direction of association between genotype and blood pressure changed with time. Finally, in models controlling for potential confounding by population stratification, we observed evidence of within-family effects for blood pressure (diastolic blood pressure beta=1.77 mm Hg per copy of the A allele, P=0.004; systolic blood pressure beta=2.04 mm Hg per copy of the A allele, P=0.07; mean arterial blood pressure beta=1.85 mm Hg per copy of the A allele, P=0.01) and for hypertension (odds ratio=1.26 per copy of the A allele; P=0.08). No association was observed for obesity. Associations with diabetes were similar in magnitude as reported previously but were not statistically significant. These data demonstrate association between genetic variability at 11betaHSD1 with hypertension, but these effects are modified by environmental factors.

11-beta-Hydroxysteroid Dehydrogenase Type 1↗
PubMed2004

Subcutaneous abdominal preadipocyte differentiation in vitro inversely correlates with central obesity.

Expansion of adipose tissue mass results from increased number and size of adipocyte cells. We hypothesized that subcutaneous abdominal preadipocytes in obese individuals might have an intrinsically higher propensity to differentiate into adipocytes. Thus we investigated the relationship between obesity and the level of in vitro preadipocyte differentiation in Pima Indians. Subcutaneous abdominal stromal vascular fractions containing preadipocytes were cultured from 58 nondiabetic subjects [31 M/27 F, 30 +/- 6 yr, body fat 34 +/- 8% by dual-energy X-ray absorptiometry (means +/- SD)]. The average percentage of preadipocyte differentiation (PDIFF; cell count by microscopy) was 11 +/- 11% (range 0.2-51%). PDIFF correlated negatively with percent body fat (r = -0.35, P = 0.006) and waist circumference (r = -0.45, P = 0.0004). Multiple regression analysis indicated that waist circumference (P = 0.01), sex (P = 0.01), and percent body fat (P = 0.05) were significant determinants of PDIFF. Molecular characterization of predifferentiated cultured cells was performed by real-time PCR measurements of glucocorticoid receptor-alpha (GRalpha), insulin-like growth factor I receptor (IGF-IR), peroxisome proliferator-activated receptor-gamma (PPARgamma), enhancer-binding protein GATA-3, CCAAT/enhancer-binding protein-alpha undifferentiated protein (CUP/AP-2alpha), and endothelial cell-specific marker 2 (ECSM2). The mRNA concentrations of GRalpha correlated with PDIFF (r = 0.29, P = 0.03), but the others did not (IGF-IR, r = 0.003, P = 1.0; PPARgamma, r = -0.1, P = 0.5; GATA-3, r = 0.02, P = 0.9; CUP/AP-2alpha, r = -0.2, P = 0.1; ECSM2, r = 0.04, P = 0.7). Contrary to our hypothesis, the results may indicate a blunted in vitro differentiation potential of preadipocytes in centrally obese individuals. The lower differentiation potential of preadipocytes in the obese subjects might be due, at least partly, to decreased glucocorticoid receptor expression.

Abdomen↗
PubMed2004

Endogenous glucose production, insulin sensitivity, and insulin secretion in normal glucose-tolerant Pima Indians with low birth weight.

Individuals with low birth weight (LBW) are at increased risk of developing type 2 diabetes in later life. Whether impairments in endogenous glucose production (EGP), insulin action, insulin secretion, or a combination thereof account for this association is unclear. We, therefore, examined these parameters in Pima Indians with normal glucose tolerance. Body composition, glucose and insulin responses during a 75-g oral glucose tolerance test (OGTT), EGP, insulin-stimulated glucose disposal during low- and high-dose insulin infusion (M-low and M-high, hyperinsulinemic glucose clamp), and acute insulin response (AIR) to a 25-g intravenous glucose challenge were measured in 230 Pima Indians (147 men and 83 women, aged 25 +/- 0.4 years [mean +/- SE; range, 18 to 44]) with normal glucose tolerance. A subgroup of 63 subjects additionally underwent biopsies of subcutaneous adipose tissue for determination of adipocyte cell size and lipolysis. Subjects in the lowest quartile of birth weight (birth weight: 2,891 +/- 33 g, LBW, n = 58) were compared to those whose birth weight was in the upper 3 quartiles (birth weight: 3,657 +/- 28 g, NBW, n = 172). Age- and sex-adjusted body mass index (BMI), percent body fat, and waist-to-thigh ratio (WTR) were similar in LBW and NBW subjects. Suppression of EGP during the clamp was less in LBW than in NBW subjects before (P = .002) and after adjustment for age, sex, percent body fat, and M-low (P = .02). M-low and M-high were less in LBW than in NBW subjects before (P = .05 and P = .01) and after adjustment for age, sex, percent body fat, and WTR (P = .04 and P = .05). AIR was not different in LBW compared to NBW subjects before adjustments (P = .06), but it was lower in LBW than in NBW subjects after adjustment for age, sex, percent body fat, and M-low (P = .02), suggesting that AIR did not increase appropriately for the decrease in insulin-stimulated glucose disposal (M). In addition, average adipocyte cell size (P = .08) and basal lipolysis (P = .02) were higher in the LBW than in the NBW group. These results show that Pima Indians with LBW manifest a variety of impairments in metabolism in adulthood. Among these, a lesser insulin-stimulated suppression of EGP and a lesser insulin secretory capacity are the predominant ones. We conclude that interaction of multiple defects may contribute to increased susceptibility to type 2 diabetes among individuals with LBW.

Adipocytes↗
PubMed2004

The intra- and inter-instrument reliability of DXA based on ex vivo soft tissue measurements.

OBJECTIVE: Comparison of ex-vivo soft tissue measurements using the GE/Lunar pencil (DPX-L; GE/Lunar Co., Madison, WI) and fan beam (Prodigy dual-energy X-ray absorptiometers (DXA) GE/Lunar Co.). RESEARCH METHODS AND PROCEDURES: Intra-instrument reliability was assessed by repeatedly scanning soft tissue phantoms for lean tissue (water) and fat tissue (methanol) using one DPX-L and two identical Prodigy DXAs at fast, medium, and slow scan modes. For each machine, 10 scans of each phantom were performed at each scan speed. The number of scans per instrument totaled 60. Data were analyzed using ANOVA to ascertain whether scan speed affected the intra-instrument reliability and to test whether soft tissue measurements differed among instruments. Percentage fat (phantom density) was the outcome variable. RESULTS: Intra-instrument reliability, expressed as coefficient of variation, ranged between 0.7% and 5.2% for the DPX-L and 0.4% and 4.5% for the Prodigy, with the lowest coefficients of variation observed when scanning the fat tissue phantom. Scan speed also affected the intra-instrument reliability (p < 0.01). Furthermore, differences in the measurement of percentage body fat for both the lean and fat tissue phantoms were observed among all three absorptiometers (all p < 0.01). After adjusting for scan speed, differences persisted for all three instruments. DISCUSSION: Intra- and inter-instrument reliability of DXA machines, even those from the same manufacturer, remains unpredictable. Thus, when measuring body composition using DXA, it is important to consider that even in the absence of measurement bias, the use of different DXA machines, particularly when using a variety of speed settings, will increase the residual error around the true value.

Absorptiometry, Photon↗
PubMed2004

Taste preferences and body weight changes in an obesity-prone population.

BACKGROUND: Taste preferences for highly palatable foods rich in sugar and fat may underlie the current epidemic of obesity. OBJECTIVE: This study aimed to determine whether the hedonic response to sweet and creamy solutions differs between whites and Pima Indians and whether a preference for these tastes predicts weight gain. DESIGN: One hundred twenty-three Pima Indian and 64 white volunteers taste tested solutions of nonfat milk (0.1% fat), whole milk (3.5% fat), half and half (11.3% fat), and cream (37.5% fat) containing 0%, 5%, 10%, or 20% sugar by weight. Solutions were rated for perceived sweetness, creaminess, and pleasantness (hedonic response) on a 100-mm visual analogue scale. Follow-up body weight was measured in 75 Pima Indians 5.5 +/- 3.0 y ( +/- SD) after baseline taste testing. RESULTS: The Pima Indians had a significantly (P = 0.006) lower hedonic response than did the whites (repeated-measures analysis of variance). Neither body size (P = 0.56) nor adiposity (P = 0.86) was a significant predictor of the hedonic response. There was a positive correlation (r = 0.28, P = 0.01) between the maximal hedonic response at baseline and subsequent weight gain in the Pima Indians. CONCLUSION: Although the Pima Indians liked sweet and creamy solutions less than the whites did, a heightened hedonic response for these solutions among the Pima Indians was associated with weight gain.

Adult↗
PubMed2004

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.

Adult↗
PubMed2004

Melanocortin 4 receptor gene variation is associated with severe obesity in Pima Indians.

Heterozygous coding mutations in the melanocortin 4 receptor gene (MC4R) are the most common genetic causes of severe human obesity identified to date. To determine whether MC4R has a role in causing severe obesity in Pima Indians, we sequenced the coding region of this gene in 426 full-heritage, non-first-degree related, adult Pima Indians (300 severely obese and 126 nondiabetic nonobese control subjects). Three coding variations were detected as heterozygotes only in severely obese subjects. One variation, detected in three obese subjects, was a novel single-base insertion (A) at nucleotide 100, and it predicted a frameshift and premature STOP at codon 37. The second variant, detected in 10 obese subjects, predicted a previously identified arginine-to-glutamine substitution at codon 165, and the third variant, detected in one obese subject, predicted a novel glycine-to-serine substitution at codon 231. Three polymorphisms were also identified in the 5' untranslated region, but these variants were detected in both obese and lean subjects and had similar allele frequencies. We conclude that variations in MC4R may account for a small portion of obesity in Pima Indians, but they do not explain the overall high prevalence of obesity in this Native American population.

Adult↗