学龄儿童β3-肾上腺素能受体基因变异的分布

目的 了解学龄儿童中β3-肾上腺索能受体（β3-AR)基因氧基酸序列第64位密码子上的色氨酸(Trp64Arg)变异型的分布特点及其与肥胖的关系，方法 用限制性片段基困长度多态性法对177名儿蛊进行了基因多态性检测，同时测量身高、体重。结果 变异型等位基因(C)在被调查对象中出现的频率为0．240，其中男童为0226，女童为0．267。肥胖女童中变异等位基因(C)、Trp64Arg变异基因型的出现频率明显高于正常体重者。有父母肥胖或有母亲肥胖的家庭中，女童出现Trp64Arg变异的频率分别为713．3％，71．4％。具有Trp64Arg变异儿童的体重、BM1明显较高，具有Trp64Arg变异的女童发生肥胖的危险性为4．5，结论 基因Trp64Arg变异在学龄儿童中有一定的分布，且以肥胖女童为多。     

Variability in energy expenditure and its components

PURPOSE OF REVIEW: To review factors contributing to variation in total daily energy expenditure and its primary components: (1) resting metabolic rate; (2) diet-induced thermogenesis; and (3) activity thermogenesis, including exercise energy expenditure and nonexercise activity. For each component, the expected magnitude of intra-individual variability is also considered. We also reviewed studies that quantified the variability in 24 h energy expenditure. RECENT FINDINGS: In humans, the coefficient of variation in the components of total daily energy expenditure is around 5-8% for resting metabolic rate, 1-2% for exercise energy expenditure, and around 20% for diet-induced thermogenesis. The coefficient of variance for 24 h energy expenditure measured using a room calorimeter for resting metabolic rate is around 5-10%. Thus, these measures are all rather reproducible. Total daily energy expenditure varies several-fold in humans, not due to variation in resting metabolic rate, diet-induced thermogenesis, or exercise thermogenesis, but rather, due to variations in nonexercise activity. A variety of factors impact nonexercise activity, including occupation, environment, education, genetics, age, gender, and body composition, but little is known about the magnitude of effect. SUMMARY: Resting metabolic rate, diet-induced thermogenesis, exercise energy expenditure, and 24 h energy expenditure are highly reproducible. Coefficient of variation is smallest for exercise energy expenditure, followed by resting metabolic rate, 24 h energy expenditure, and diet-induced thermogenesis. There is considerable variability in total daily energy expenditure, largely due to variations in nonexercise activity. Although the factors that impact upon nonexercise activity are understood, their contribution to variation in total daily energy expenditure is unclear.     

Meta-analysis of the association of the Trp64Arg polymorphism in the beta3 adrenergic receptor with insulin resistance

OBJECTIVE: To clarify the possible association between the Trp64Arg polymorphism and insulin resistance (IR). RESEARCH METHODS AND PROCEDURES: Articles evaluating the effect of the Trp64Arg polymorphism on IR were identified on the MEDLINE and PubMed databases from 1995 to February, 2004. After extraction of relevant data, main and subgroup meta-analyses were performed to assess the differences in IR indices between Trp/Trp and Trp/Arg genotypes. RESULTS: Forty eligible papers containing 56 subgroups were included in this meta-analysis. Among a total of 12,805 subjects, 21.9% had Trp64Arg mutation: 20.8%, heterozygotes and 1.1%, homozygotes. Significant associations were found between this mutation and some indices of IR. The weighted mean difference in fasting insulin, 120-minute insulin level after oral glucose tolerance test, and homeostasis model assessment between Arg64 and Trp64 was 0.23 [95% confidence interval (CI), 0.05 to 0.42] pM, 0.89 (95% CI, 0.30 to 1.48) pM, and 0.55 (95% CI, 0.14 to 0.96), respectively. Subgroup analysis further indicated that this significant association existed only in the Asian population (p < 0.01) and in the obese (p = 0.02) and diabetes subgroups (p = 0.03). DISCUSSION: Numerous studies have been conducted to examine the relationship between the beta3-adrenergic receptor Trp64Arg polymorphism and components of IR syndrome. However, the results have been inconsistent and have led to controversy about whether this polymorphism is associated with these clinical features. The current meta-analysis demonstrated the moderate effects of the Trp64Arg polymorphism on IR in the Asian population and in obese and diabetic subgroups.     

Increased risk of obesity resulting from the interaction between high energy intake and the Trp64Arg polymorphism of the beta3-adrenergic receptor gene in healthy Japanese men

BACKGROUND: Few studies have investigated the interaction between the Trp64Arg polymorphism of the beta3-adrenergic receptor gene (ADRB3) and environmental factors. This study aimed to investigate whether energy intake affects the relationship between this polymorphism and obesity. METHODS: Healthy Japanese men (n=295; age 46.1+/-11.5 years (mean +/-standard deviation); waist circumference 83.9+/-9.3 cm; body mass index (BMI) 23.3+/-3.3 kg/m2) recruited in a Japanese chemical industry firm were eligible for analysis. Daily energy intake, protein, fat, and carbohydrate (PFC) ratio and daily physical activity were assessed by self-reported questionnaires. Genotyping for the polymorphism was performed with written informed consent. RESULTS: When the subjects were classified into two groups according to presence of the polymorphism, the groups were not significantly different in waist circumference or BMI. Quartile classification of energy intake, however, demonstrated a significantly larger ratio of obese subjects to non-obese subjects in the group with the polymorphism in the highest 4th quartile alone. Multiple logistic regression analysis also revealed that the presence of the polymorphism increased the risk of obesity significantly in the 4th quartile alone (adjusted odds ratio=3.37, 95% confidence interval=1.12-10.2). CONCLUSION: Presence of the polymorphism alone does not significantly increase the risk of obesity. However, high energy intake interacts with the polymorphism and leads to a significant increase in risk of obesity. The Trp64Arg polymorphism of ADRB3 warrants consideration, along with other polymorphisms involved in the development of obesity, for tailor-made prevention of obesity.     

Resting energy expenditure, activity energy expenditure and total energy expenditure at age 91-96 years

There is a limited knowledge concerning energy requirements of the elderly, especially the oldest old (> 80 years). Energy requirements should be estimated from measurements of energy expenditure. For this purpose twenty-one free-living individuals (eight males, thirteen females) aged 91-96 years living in G?teborg, Sweden were studied. Total body water (TBW) measured by the doubly-labelled-water (DLW) technique was 29.5 (sd 5.4) kg in females and 35.6 (sd 4.3) kg in males. TBW measured using bioelectric impedance (BIA) was 31.6 (sd 6.4) kg in females and 42.0 (sd 7.4) kg in males. The mean difference between TBW measured by BIA and that measured by DLW was 3.54 (sd 3.6) kg (P = 0.0002). Resting metabolic rate (RMR) was measured using a ventilated-hood system and averaged 5.36 (sd 0.71) MJ/d in females (n 12) and 6.09 (sd 0.91) MJ/d in males (n 8). Difference between measured RMR and predicted BMR (n 20) was 0.015 (sd 0.86) MJ/d (NS). Total energy expenditure (TEE) measured by DLW averaged 6.3 (sd 0.81) MJ/d in females and 8.1 (sd 0.73) MJ/d in males. Activity energy expenditure (TEE - RMR), thus including diet-induced thermogenesis (DIT), averaged 0.95 (sd 0.95) MJ/d in females (n 12) and 2.02 (sd 1.13) MJ/d in males. Physical activity level (TEE/BMR) averaged 1.19 (sd 0. 19) in females and 1.36 (sd 0.21) (P = 0.08) in males. If DIT is assumed to be 10 % of the TEE, energy spent on physical activity will be very low in this population.     

Aging and energy expenditure

Whether sedentary energy expenditure is normal or lower in elderly people has not yet been clearly established. Twenty-four-hour energy expenditure (24EE) and its different components were measured by use of a respiratory chamber in elderly (17 male, 21 female; 71 +/- 6 y, mean +/- SD; 71.2 +/- 13.5 kg; 32 +/- 8% fat) and young (33 male, 31 female; 24 +/- 4 y; 84.5 +/- 23.1 kg; 25 +/- 13% fat) subjects. The elderly subjects had lower mean height (P less than 0.001), weight (P less than 0.01), and fat-free mass (P less than 0.001) but higher percent body fat (P less than 0.01) than did the young adults. Absolute 24EE, basal metabolic rate (BMR), and sleeping metabolic rate were significantly lower (P less than 0.01) in the elderly subjects than in the young subjects. However, after differences in fat-free mass, fat mass, and sex were adjusted for, only BMR was found to be lower in the elderly subjects (P less than 0.01). Despite a reduced adjusted BMR in older subjects, sedentary 24EE was decreased only in proportion to their reduced body size, suggesting that the lower energy intake reported in elderly people might be mainly related to lower physical activity in free-living conditions.     

Leptin and energy expenditure

PURPOSE OF REVIEW: A fundamental advance in our understanding of endocrine control of energy balance and body weight came with the discovery of the adipocyte-derived hormone leptin. The leptin pathway appeared to be the long-sought peripheral signal pathway from the adipose tissue to the brain involved in the regulation of feeding and energy balance. RECENT FINDINGS: Initially, leptin was considered to function as the long-sought antiobesity hormone. According to this hypothesis, rising concentrations of leptin with increasing adiposity would generate a signal to reduce food intake and increase energy expenditure in order to limit further weight gain. However, widespread resistance to the proposed antiobesity action of leptin is observed in humans, which might reflect the fact that the inability to store energy efficiently at times of abundance is evolutionarily disadvantageous. According to this alternative view, falling leptin concentrations observed during fasting act as a peripheral signal of starvation, which serves to conserve energy in the face of limited reserves. However, leptin administration failed to blunt the changes in energy expenditure during severe energy restrictions in several clinical studies. In addition, leptin therapy in several different human low-leptin states failed to affect energy expenditure in recent studies. SUMMARY: Increasing evidence from human studies suggests that leptin predominantly influences the human energy balance through appetite but appears not to be involved in regulating energy expenditure. None of the expected factors such as resting metabolic rate, total diurnal energy expenditure or dietary induced thermogenesis was related to blood leptin concentrations.     

Association of Gln223 Arg polymorphism of the leptin receptor gene with indicators of energy expenditure in obese children

ObjectiveGln223 Arg polymorphism of the leptin receptor (LEPR) gene is one of the most frequently examined polymorphisms of this gene and has been suggested to be associated with energy expenditure (EE). The aim of the present study was to investigate the association of this variant on indicators of EE—resting metabolic rate (RMR), postabsorptive and postprandial respiratory quotient (RQ), and food-induced thermogenesis (FIT)—in obese children.MethodsThe study included 486 genotyped children (obese, n = 355). RMR was measured by indirect calorimetry for 45 min. Subsequent to test-food consumption, FIT was measured in a subsample of obese children (n = 121, body mass index 31.9 kg/m² (mean ± SD 5.1).ResultsObese children with the Gln223 Gln genotype showed a significantly lower post-absorptive and postprandial RQ (P = 0.0055 versus P = 0.0002, adjusted for age, sex, and lean body mass) than did groups of children with Gln223 Arg and Arg223 Arg genotypes. No significant differences were observed in FIT and RMR among the carriers and non-carriers of the 223 Arg allele.ConclusionThe significantly lower post-absorptive and postprandial RQ in the group of Gln223 Gln genotype children indicates that the fat oxidation of these children maybe increased before and subsequent to food consumption, which can be important in the planning of diet of these children.     

The frequency of Trp64Arg polymorphism of the beta3-adrenergic receptor gene in healthy and obese Hungarian children and its association with cardiovascular risk factors

OBJECTIVE: To estimate the frequency of Arg64 allele of the beta(3)-adrenergic receptor (3-BAR) gene in healthy (H) and obese (O) Hungarian children, and to look for possible associations between this polymorphism and some clinical and metabolic characteristics of obese children. PATIENTS/METHODS: In all, 147 healthy (male: 68) and 295 obese (male: 168) children were examined. The average age of the children in the two groups was 12.4+/-1.7 vs 12.6+/-3.2, respectively. Exon 1 of 3-BAR was amplified by polymerase chain reaction and the fragments were digested with BstN1. In obese children, oral glucose tolerance test was carried out and blood pressure (BP) was checked. RESULTS: The frequency of Trp64Arg polymorphism in normal and obese Hungarian children was similar (H vs O: n=14/9.5% vs n=35/11.8%). Obese children carrying the Arg64 allele (n=35, male: 23) were compared to randomly chosen, obese children without the Arg64 allele (n=35, male: 20). A significant difference was found between the body weight (81.2+/-23.2 vs 75.6+/-17.7 kg; mean+/-s.d.; P<0.01), body fat (38.8+/-3.9 vs 36.5+/-2.3%; mean+/-s.d.; P<0.05), mean fasting insulin levels (31.4+/-16.7 vs 16.9+/-7.6 microIU/ml; P<0.001) and mean systolic BP values (125.2+/-10.1 vs 114.5+/-8.3 mmHg; P<0.001) of the two obese groups. CONCLUSIONS: The frequency of Trp64Arg polymorphism was similar in Hungary as compared to other European countries. Although the prevalence of this polymorphism was similar in H and O children, the presence of Arg64 allele seems to be associated with increased adiposity, elevated systolic BP and higher fasting insulin levels.     

Comparison of body fat distribution and blood lipid profiles according to Trp64Arg polymorphism for the beta 3-adrenergic receptor gene in Korean middle-aged women

The aim of this study was to determine whether there was an association between body fat distribution, blood lipid profiles, and beta 3-adrenergic receptor gene polymorphism in Korean middle-aged women. Subjects were grouped according to BMI as obese (> or = 5 BMI, n = 95) or non-obese (BMI<25, n = 93). The Trp64Arg mutation of the beta 3-adrenergic receptor gene was detected by PCR-RFLP. Skinfold thickness, body circumference, intra-abdominal fat area by CT, and blood lipid profiles were also measured. Data were compared using ANOVA, Bonferroni t-test, and Chi-square. Significance for statistical analyses were set at p<0.05. In the obese group, 63.16% were Trp64Trp homozygotes and 36.84% were Trp64Arg heterozygotes, compared to 80.65% who were Trp64Trp homozygotes and 19.35% who were Trp64Arg heterozygotes in the non-obese group. These results indicated a significant (chi-square = 4.943, p<0.05) difference between the two groups. Frequency of the Arg64 allele in the obese group (16.84%) showed a significant (chi-square = 4.185, p<0.05) difference as compared to the non-obese group (9.68%). Skinfold thickness and body circumference of the Trp64Arg heterozygote group showed a consistent increase as compared to the Trp64Trp homozygote group. Visceral fat area and VSR of Trp64Arg heterozygote group showed a higher tendency than Trp64Trp homozygotes in the obese group, but these differences were not statistically significant. In conclusion, the Trp64Arg polymorphism of the beta 3-adrenergic receptor gene is associated with obesity in middle-aged Korean women, but it is difficult to suggest the prominent association of the Trp64Arg polymorphism of the beta 3-adrenergic receptor gene with prevalence of abdominal obesity or dyslipidemia in Korean middle-aged women.     

DXA: potential for creating a metabolic map of organ-tissue resting energy expenditure components

OBJECTIVE: This study tested the hypothesis that tissue-organ components can be derived from DXA measurements, and in turn, resting energy expenditure (REE) can be calculated from the summed heat productions of DXA-estimated brain, skeletal muscle mass (SM), adipose tissue, bone, and residual mass (RM). RESEARCH METHODS AND PROCEDURES: Subjects were divided into five groups of adults <50 years of age. The specific metabolic rate of RM was developed in 13 Group I healthy subjects and a DXA-brain mass prediction formula in 52 Group II subjects. SM, adipose tissue, and bone models were developed based on earlier reports. The composite REE prediction model (REEp) was tested in 154 Group III subjects in whom REEp was compared with measured REE (REEm). Features of the developed model were determined in 94 normal-weight men and women (Group IV) and seven spinal cord injury patients and healthy matched controls (Group V). RESULTS: REEp and REEm in Group III were highly correlated (y = 0.85x + 233; r = 0.82, p < 0.001), and no bias was detected. Both REEm (mean +/- SD, 1,579 +/- 324 kcal/d) and REEp (1,585 +/- 316 kcal/d) were also highly correlated (r values = 0.85 to 0.98; p values < 0.001) and provided similar group values to REE estimated by the Harris-Benedict equations (1,597 +/- 279 kcal/d) and Wang's composite fat-free mass-based REE equation (1,547 +/- 248 kcal/d). New insights into the sources and distribution of REE were provided by analysis of the demonstration groups. DISCUSSION: This approach offers a new practical and educational opportunity to examine REE in subject groups using modeling strategies that reveal the magnitude and distribution of fundamental somatic heat-producing units.     

Estimation of total daily energy expenditure and its components by monitoring the heart rate of Japanese endurance athletes

The estimation of total daily energy expenditure (TEE) or the energy needs of athletes is important for maintaining a proper energy balance during training. This study was conducted to measure the TEE of Japanese middle- and long-distance runners using a heart-rate monitoring method (the HR method), and to ascertain the impact of three key energy expenditure (EE) components occurring within the day: sleep, exercise (training) and inactivity (other daily habitual activities). Additionally, energy balance was evaluated by comparing TEE with energy intake (EI). The mean TEE of six male athletes aged 19-21 y was 4,514+/-739 kcal/d and their mean EI was 3,784+/-91 kcal/d during the training period of 11 d. This negative energy balance led to a significant decline in body weight (p<0.01), indicating that proper care should be taken to balance energy during training. The mean daily EEs during sleep, inactivity, and exercise were 536+/-46 (12.0% of TEE), 1,722+/-145 (38.7%), and 2,255+/-658 (49.3%) kcal/d, respectively. There was a significant correlation between TEE and exercise EE (p<0.01) in the athletes. The TEE of the endurance athletes was higher than expected and significantly affected by exercise EE, indicating that the TEE of athletes, in general, must be carefully evaluated before incorporating nutritional support for them.     

The Trp64Arg polymorphism of the beta3-adrenergic receptor gene is not associated with training-induced changes in body composition: The HERITAGE Family Study

OBJECTIVE: To investigate the association between the Trp64Arg polymorphism of the beta3-adrenergic receptor gene and changes in body composition in response to endurance training. RESEARCH METHODS AND PROCEDURES: Adult sedentary white and black subjects participating in the HERITAGE Family Study were measured before and after 20 weeks on endurance training for the body mass index, fat mass, percentage of body fat, fat-free mass, sum of eight skinfolds, and subcutaneous, visceral, and total abdominal fat areas. The association between the Trp64Arg polymorphism and the response phenotypes, computed as the difference between pre- and post-training values, was tested by analysis of covariance separately in men and women. The gene by race interaction term was also tested. RESULTS: No race differences were observed for allelic and genotype frequencies. Training resulted in significant reduction of body fat in both men and women. No association of the Trp64Arg polymorphism was observed with training-induced changes for any of the body composition phenotypes in both men and women. DISCUSSION: These results suggest that the Trp64Arg polymorphism of the beta3-adrenergic receptor gene is not related to changes in body composition in response to exercise training.     

β3肾上腺素能受体基因Trp64Arg突变与胰岛素抵抗相关

目的采用聚合酶链式反应-限制性酶切片段长度多态性(PCR-RFLP)技术,探讨β3肾上腺素能受体(β3 adrenergic re-ceptor,β3AR)基因Trp64Arg突变与中国人胰岛素抵抗(IR)的相关性。方法用PCR-RFLP技术,检测2型糖尿病组(DM组)和正常对照组(N组)β3AR基因型,并测量血糖(FPG)、血浆胰岛素(FINS)等临床生化指标。以FPG×FINS/22.5计算胰岛素抵抗指数(HO-MA-IR),以BM I<25的健康人HOMA-IR的75分位值为界,将DM组分为胰岛素相对敏感组及相对抵抗组。结果与无突变者相比,β3AR Trp64Arg突变携带者BM I升高,2组间WHR、血脂、血压、心率、病程及发病年龄差异无统计学意义。胰岛素相对抵抗组68例,占DM组的56.7%,提示2型DM患者大部分存在IR。胰岛素相对抵抗组β3AR Trp/Arg基因型频率明显高于胰岛素相对敏感组,提示β3AR Trp64Arg基因突变参与IR的发生。结论β3AR Trp64Arg突变参与中国人体重的调节,可能是IR的危险因素之一。     

Total energy expenditure in the elderly

Chronic diseases and disabilities increase with age, affecting more than 60% of those over 75 y, and limiting activities in about half of them. Therefore, total energy expenditure (TEE) and its components are assessed separately in health and disease. An analysis of 568 doubly labelled water measurements in 'healthy' subjects (184 measurements in subjects over 65 years) suggests that there is a decrease of 0.69 and 0.43 MJ/day/decade respectively in men (standard weight 75 kg) and women (standard weight 67 kg). Physical activity (PA) accounted for 46% of the decrease in TEE, basal metabolic rate (BMR) for 44% of the decrease and thermogenesis (T) for the remaining 10%. TEE was found to be 10.79+/-2.09 and 8.62+/-1.49 MJ/day in 150 men and 100 women aged over 60 y, respectively. Of the total variance in TEE, measured with doubly labelled water over a 2 week period, 69% was considered to be due to differences between individuals, and 31% to differences within individuals. The variance due to PA plus T was threefold greater than that due to BMR. Physiological factors were far more important than methodological factors in influencing measurements of TEE, BMR and PA+T. An analysis of 136 measurements of TEE (doubly labelled water and bicarbonate-urea methods) in free-living elderly patients suffering from a variety of diseases suggests a frequent decrease in TEE, which may occur despite an increase in BMR. This is largely due to a reduction is PA (eg up to approximately 50% reduction), but in some cases it is also due to a reduction in BMR (loss of body weight). More comprehensive information is required about TEE and its components, partly because of a probable selection bias in recruitment of subjects participating in specific tracer studies, and partly because of the variable effects of different diseases and factors that operate at different times in the course of the same disease.     

Comprehensive assessment of the components of energy expenditure in infants using a new infant respiratory chamber.

BACKGROUND: Current methods for energy expenditure (EE) measurements in term infants do not include simultaneous measurements of basal and sleeping metabolic rates (BMR and SMR) or a measure of physical activity (PA). Furthermore, prediction equations for calculating EE are not appropriate for use in infants with metabolic disorders. OBJECTIVE: To develop and utilize a new infant respiratory chamber for simultaneous measurements of EE (kJ/d), preprandial BMR (kJ/d), SMR (kJ/d) and an index of PA (oscillations/min/kg body weight) in infants with a variety of metabolic disorders, for up to four hours in a hospital setting, while allowing parental interaction in a comfortable environment. METHODS: We obtained simultaneous measurements of EE, BMR, SMR and PA in 21 infants (66+/-73 days of age, 4.5+/-1.7 kg body weight, 55+/-8 cm in length and 16+/-7% body fat) using our new infant respiratory chamber. Six of these infants were healthy, seven had thyroid dysfunction, five were HIV-exposed, one had AIDS, one had intrauterine and postnatal growth retardation and one was a hypothermic preterm infant. Energy expenditure, BMR and SMR were extrapolated for 24 hours. Body composition was estimated by skin-fold thickness, using age-appropriate formulae. Basal metabolic rate obtained with the infant respiratory chamber was compared to BMR that was calculated using the appropriate World Health Organization (WHO) equations. RESULTS: In all infants both extrapolated 24-hour EE and BMR correlated with fat-free mass (r = 0.89, p<0.01 and r = 0.88, p<0.01 respectively). Twenty-four hour EE also correlated with PA (r = 0.52, p<0.05). The HIV-exposed infants had higher BMR (p<0.05) than that calculated by the appropriate WHO equation. We found that the caloric requirements for the infant with growth retardation were underestimated based on the infant's weight and age. CONCLUSIONS: The infant respiratory chamber can measure all of the main components of EE. Some of the results obtained differed significantly from those obtained by the WHO equations; therefore, the new infant respiratory chamber is necessary for estimating EE in infants with metabolic and growth disorders.     

The measurement of energy expenditure

This is a brief account of the development of energy expenditure measurements, from speculations by early philosophers on the nature of the "innate fire," through the beginnings of quantitative animal calorimetry and to the combined material and energy balances of Rubner and of Atwater and Benedict, which established the science of nutritional energy. The equivalence of oxidation rate and heat loss led to the simplification of indirect calorimetry, followed by the era of studies of basal metabolic rate. Current practices are reviewed for measuring energy expenditure by indirect calorimetry (respiration chambers, ventilated hoods, doubly labeled water) and direct calorimetry (rooms, suits). Because problems remain in the exact account of energy balance during weight change, growth, pregnancy and exercise, perhaps it may be time to combine once again carbon balance with energy balance, using modern methods.