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Background: The specific resting metabolic rates ([K.sub.i]; in kcal x [kg.sup.-1] x [d.sup.-1]) of major organs and tissues in adults were suggested by Elia (in Energy metabolism: tissue determinants and cellular corollaries. New York, NY: Raven Press, 1992) to be as follows: 200 for liver, 240 for brain, 440 for heart and kidneys, 13 for skeletal muscle, 4.5 for adipose tissue, and 12 for residual organs and tissues. However, Ella's [K.sub.i] values have never been fully evaluated. Objectives: The objectives of the present study were to evaluate the applicability of Elia's [K.sub.i] values across adulthood and to explore the potential influence of age on the [K.sub.i] values. Design: A new approach was developed to evaluate the [K.sub.i] values of major organs and tissues on the basis of a mechanistic model: REE = [summation]([K.sub.i] x [T.sub.i]), where REE is whole-body resting energy expenditure measured by indirect calorimetry, and [T.sub.i] is the mass of individual organs and tissues measured by magnetic resonance imaging. With measured REE and [T.sub.i], marginal 95% CIs for [K.sub.i] values were calculated by stepwise univariate regression analysis. An existing database of nonobese, healthy adults [n = 131; body mass index (in kg/[m.sup.2]) 50 y (n = 37). Results: Elia's [K.sub.i] values were within the range of 95% CIs in the young and middle-age groups. However, Ella's [K.sub.i] values were outside the fight boundaries of 95% CIs in the >50-y group, which indicated that Ella's study overestimated [K.sub.i] values by 3% in this group. Age-adjusted [K.sub.i] values for adults aged >50 y were 194 for liver, 233 for brain, 426 for heart and kidneys, 12.6 for skeletal muscle, 4.4 for adipose tissue, and 11.6 for residuals. Conclusion: The general applicability of Elia's [K.sub.i] values was validated across adulthood, although age adjustment is appropriate for specific applications. Am J Clin Nutr 2010;92:1369-77. doi: 10.3945/ajcn.2010.29885.

The increase in childhood obesity mainly reflects increased energy intake. However, it is not clear which food categories are responsible for this increase. Food availability data, which are calculated from annual food production, imports, beginning stocks, subtracting exports, ending stocks, and nonfood uses, provide clues about which categories are the primary contributors. Data from 1909 to 2007 show increases in per capita availability of several product classes: added oils increased from 16.1 to 39.4 kg/y, meat increased from 56.3 to 91.2 kg/y, cheese increased from 1.7 to 14.9 kg/y, and frozen dairy products increased from 0.7 to 11.5 kg/y. From 1970 to 2007, per capita availability of sweeteners increased from 54.1 to 62.0 kg/y. Carbonated beverage availability has increased, partly at the expense of fluid milk. Flour and cereal availability decreased from 1909 until the late 1960s but rebounded thereafter. Availability of fruit, fruit juices, and vegetables has increased. We conclude that the major contributors to increased energy intake over the last century are oils, shortening, meat, cheese, and frozen desserts, with more recent increases in added sweeteners, fruit, fruit juices, and vegetables. These changes may have influenced the prevalence of childhood obesity. doi: 10.3945/ajcn.2010.28701G.

The prevalence and severity of obesity have increased in recent years, likely the result of complex interactions between genes, dietary intake, physical activity, and the environment. The expression of genes favoring the storage of excess calories as fat, which have been selected for over many millennia and are relatively static, has become maladaptive in a rapidly changing environment that minimizes opportunities for energy expenditure and maximizes opportunities for energy intake. The consequences of childhood and adolescent obesity include earlier puberty and menarche in girls, type 2 diabetes and increased incidence of the metabolic syndrome in youth and adults, and obesity in adulthood. These changes are associated with cardiovascular disease as well as with several cancers in adults, likely through insulin resistance and production of inflammatory cytokines. Although concerns have arisen regarding environmental exposures, there have been no formal expert recommendations. Currently, the most important factors underlying the obesity epidemic are the current opportunities for energy intake coupled with limited energy expenditure. doi: 10.3945/ajcn.2010.28701B.

Background: When the resting energy expenditure (REE) of overweight and obese adolescents cannot be measured by indirect calorimetry, it has to be predicted with an equation. Objective: The aim of this study was to examine the validity of published equations for REE compared with indirect calorimetry in overweight and obese adolescents. Design: Predictive equations based on weight, height, sex, age, fat-free mass (FFM), and fat mass were compared with measured REE. REE was measured by indirect calorimetry, and body composition was measured by dual-energy X-ray absorptiometry. The accuracy of the REE equations was evaluated on the basis of the percentage of adolescents predicted within 10% of REE measured, the mean percentage difference between predicted and measured values (bias), and the root mean squared prediction error (RMSE). Results: Forty-three predictive equations (of which 12 were based on FFM) were included. Validation was based on 70 girls and 51 boys with a mean age of 14.5 y and a mean ([+ or -]SD) body mass index SD score of 2.93 [+ or -] 0.45. The percentage of adolescents with accurate predictions ranged from 74% to 12% depending on the equation used. The most accurate and precise equation for these adolescents was the Molnar equation (accurate predictions: 74%; bias: -1.2%; RMSE: 174 kcal/d). The often-used Schofield-weight equation for age 10-18 y was not accurate (accurate predictions: 50%; bias: +10.7%; RMSE: 276 kcal/d). Conclusions: Indirect calorimetry remains the method of choice for REE in overweight and obese adolescents. However, the sex-specific Molnar REE prediction equation appears to be the most accurate for overweight and obese adolescents aged 12-18 y. This trial was registered at www.trialregister.nl with the Netherlands Trial Register as ISRCTN27626398. doi: 10.3945/ajcn.2009.28330.

Background: Melanocortin-4-receptor (MC4R) haploinsufficiency is the most common form of monogenic obesity; however, the frequency of MC4R variants and their functional effects in general populations remain uncertain. Objective: The aim was to identify and characterize the effects of MC4R variants in Hispanic children. Design: MC4R was resequenced in 376 parents, and the identified single nucleotide polymorphisms (SNPs) were genotyped in 613 parents and 1016 children from the Viva 1a Familia cohort. Measured genotype analysis (MGA) tested associations between SNPs and phenotypes. Bayesian quantitative trait nucleotide (BQTN) analysis was used to infer the most likely functional polymorphisms influencing obesity-related traits. Results: Seven rare SNPs in coding and 18 SNPs in flanking regions of MC4R were identified. MGA showed suggestive associations between MC4R variants and body size, adiposity, glucose, insulin, leptin, ghrelin, energy expenditure, physical activity, and food intake. BQTN analysis identified SNP 1704 in a predicted micro-RNA target sequence in the downstream flanking region of MC4R as a strong, probable functional variant influencing total, sedentary, and moderate activities with posterior probabilities of 1.0. SNP 2132 was identified as a variant with a high probability (1.0) of exerting a functional effect on total energy expenditure and sleeping metabolic rate. SNP rs34114122 was selected as having likely functional effects on the appetite hormone ghrelin, with a posterior probability of 0.81. Conclusion: This comprehensive investigation provides strong evidence that MC4R genetic variants are likely to play a functional role in the regulation of weight, not only through energy intake but through energy expenditure. doi: 10.3945/ajcn.2009.28514.

Background: Few questionnaires that assess usual physical activity have been reported to be valid for all different subdimensions of physical activity. Objective: The objective was to assess the validity and reliability of the Recent Physical Activity Questionnaire (RPAQ), which assesses usual physical activity (PA) in 4 domains (work, travel, recreation, and domestic life). Design: Total energy expenditure (TEE) was measured for 14 d by using the doubly labeled water technique combined with a measure of resting metabolic rate to yield PA energy expenditure (PAEE) in 25 men and 25 women. Simultaneously, intensity of activity was measured by using combined heart rate and movement sensing for 11 d. Repeatability of the RPAQ was assessed in an independent sample of 71 women and 60 men aged 31-57 y. Results: Estimated TEE and PAEE were significantly associated with criterion measures (TEE: r = 0.67; PAEE: r = 0.39) with mean ([+ or -] SD) biases of -3452 [+ or -] 2025 kJ/d and -13 [+ or -] 24 kJ * [d.sup.-1] * [kg.sup.-1]. The correlation between self-reported and measured time spent was significant for vigorous PA (r = 0.70) and marginally insignificant for sedentary time (r = 0.27, P = 0.06). The mean biases were relatively small for sedentary time and vigorous PA: 0.7 [+ or -] 2.8 h/d and -12 [+ or -] 24 min/d, respectively. The intraclass correlation coefficient for repeatability of total PAEE (U/d) was 0.76 (P < 0.0001). Conclusion: The RPAQ is the first questionnaire with demonstrated validity for ranking individuals according to their time spent at vigorous-intensity activity and overall energy expenditure. doi: 10.3945/ajcn.2009.28432.

Background: Weight loss leads to reduced resting energy expenditure (REE) independent of fat-free mass (FFM) and fat mass (FM) loss, but the effect of changes in FFM composition is unclear. Objective: We hypothesized that a decrease in REE adjusted for FFM with weight loss would be partly explained by a disproportionate loss in the high metabolic activity component of FFM. Design: Forty-five overweight and obese women [body mass index (in kg/[m.sup.2]): 28.7-46.8] aged 22-46 y followed a low-calorie diet for 12.7 [+ or -] 2.2 wk. Body composition was measured by magnetic resonance imaging, dual-energy X-ray absorptiometry, and a 4-compartment model. REE measured by indirect calorimetry (REEm) was compared with REE calculated from detailed body-composition analysis (REEc) by using specific organ metabolic rates (ie, organ REE/mass). Results: Weight loss was 9.5 [+ or -] 3.4 kg (8.0 [+ or -] 2.9 kg FM and 1.5 [+ or -] 3.1 kg FFM). Decreases in REE (-8%), free triiodothyronine concentrations (-8%), muscle (-3%), heart (-5%), liver (-4%), and kidney mass (-6%) were observed (all P < 0.05). Relative loss in organ mass was significantly higher (P < 0.01) than was the change in low metabolically active FFM components (muscle, bone, and residual mass). After weight loss, REEm--REEc decreased from 0.24 [+ or -] 0.58 to 0.01 [+ or -] 0.44 MJ/d (P = 0.01) and correlated with the decrease in free triiodothyronine concentrations (r = 0.33, P < 0.05). Women with high adaptive thermogenesis (defined as REEm--REEc < -0.17 MJ/d) had less weight loss and conserved FFM, liver, and kidney mass. Conclusions: After weight loss, almost 50% of the decrease in REEm was explained by losses in FFM and FM. The variability in REEm explained by body composition increased to 60% by also considering the weight of individual organs.

Background: Homozygosity for 2 protein-altering polymorphisms in the melanocortin-3 receptor gene (MC3R) coding sequence, C17A and G241A, has been reported to be associated with an obesity phenotype in children, yet how these polymorphisms affect energy homeostasis is unknown. Association between adult body weight and +2138InsCAGACC. another variant in the 3' untranslated region of MC3R, has also been described. Objective: The objective of this study was to examine associations of C17A + G241A and +2138InsCAGACC MC3R variants with children's energy balance. Design: Children aged 6-19 y were genotyped for MC3R C17A, G241 A, and +21381nsCAGACC. Subjects underwent studies of energy intake from a 9835-kcal food array (n = 185), resting energy expenditure (REE) by using indirect calorimetry (n = 302). or total daily energy expenditure (TEE) by using doubly labeled water (n = 120). Linear regression was used to examine the associations between MC3R polymorphisms and the measures of energy balance. Results: Body mass index and fat mass were greater in those with double homozygosily for C17A + G241A (P = 0.001 ). After accounting for covariates (including body composition), the number of minor C17A + G241A alleles was associated with significantly greater energy intake ([beta] = + 0.15, P = 0.02) but not altered REE or TEE. No significant associations were observed between +2138InsCAGACC and measnres of either fat mass of energy balance. Conclusions: C17A + G241A polymorphisms may be associated with pediatric obesity because of greater energy intake rather than because of diminished energy expenditure. +2138InsCAGACC does not appear to be associated with obesity or measures of energy balance in children.

Background: In contrast to the general population, a higher body mass index is associated with better survival among hemodialysis patients. Theoretically, high energy supplementation in these patients ought to lead to weight gain over time, but the benefits of this strategy are unclear. Objective: The objective was to assess whether high energy supplementation in nondiabetic hemodialysis patients might adversely affect insulin resistance--a known risk factor for cardiovascular disease. Design: We first investigated the association between body fat mass and insulin resistance (homeostasis model assessment of insulin resistance; HOMA-IR) in nondiabetic hemodialysis patients in a cross-sectional analysis (study 1). Of the 106 individuals studied, 55 were randomly assigned to either high energy supplementation (an extra 475 kcal/d; n = 28) or not (n = 27) for 12 wk to assess prospective changes in body fat mass and insulin resistance (study 2). Results: In study 1, body fat mass (P < 0.05) and C-reactive protein (CRP) (P < 0.05) each contributed independently to HOMAIR. In study 2, 41 patients completed the study. The 20 patients who received high energy supplementation had a significantly greater increase in body fat mass (P < 0.05), CRP (P < 0.05), and HOMAIR (P < 0.001) than did the 21 controls. Conclusions: Body fat mass and CRP are primary determinants of insulin resistance in nondiabetic hemodialysis patients. High energy supplementation, because it increases adiposity and inflammation, exacerbates insulin resistance. A long-term study is needed to clarify the metabolic effects of high energy supplementation on cardiovascular disease outcomes in hemodialysis patients.

Background: No evidence-based recommendations exist concerning what dietary macronutrient composition optimizes weight loss during lactation while maintaining milk production. Objectives: The study was designed to test the following hypotheses: compared with a reduced-calorie, high-carbohydrate (H-CHO) diet, an isonitrogenous, isocaloric high-fat (H-F) diet will decrease milk production and carbohydrate oxidation, increase gluconeogenesis and hexoneogenesis, and not affect energy balance. Design: Seven healthy lactating mothers and their infants were studied on 2 occasions in random order for 8 d separated by 1-2 wk. On one occasion, the subjects received the H-F (30% of energy as carbohydrate and 55% as fat) diet and on the other occasion received the H-CHO (60% of energy as carbohydrate and 25% as fat) diet. Milk production, infant intakes, and substrate and hormone concentrations were measured. Glucose rates of appearance, production, gluconeogenesis, glycogenolysis, and hexoneogenesis were measured by using stable-isotope gas chromatography--mass spectrometric techniques, and energy expenditure and substrate oxidation were measured by using indirect calorimetry. Results: Milk volume, lactose, and protein concentrations were unaffected. Milk fat, energy, and infant intakes were higher (P < 0.05) during the H-F diet. Neither gluconeogenesis nor hexoneogenesis was different. During the H-F diet, energy expenditure and fat and protein oxidation rates were higher (P < 0.05), and the daily energy balance deficit was greater (P < 0.01). Conclusions: Milk fat, energy output, and energy expenditure were higher during the H-F diet, which resulted in a greater negative energy balance. The lactating mothers adapted to a low carbohydrate intake by decreasing carbohydrate oxidation. Additional studies are warranted to determine whether a hypocaloric H-F diet might promote weight loss to a greater extent than the H-CHO diet while maintaining milk production.

Background: The presence of fat in the small intestine modulates gastrointestinal motility, stimulates plasma cholecystokinin and peptide YY release, and suppresses appetite and energy intake. These effects are dependent on the lipolysis of fat. Objective: Our aim was to evaluate the hypothesis that increasing the droplet size of a fat emulsion would attenuate these effects. Design: Ten healthy, lean males were studied on 4 separate occasions in single-blind randomized order. Antropyloroduodenal pressures, plasma triglycerides, cholecystokinin, peptide YY, and appetite were measured during 120-min intraduodenal infusions of fat emulsions comprising 3 different droplet sizes: 1) 0.26 [micro]m (LE-0.26), 2) 30 [micro]m (LE-30), and 3) 170 [micro]m (LE-170) in addition to saline (control). Energy intake at a buffet lunch was quantified immediately after the infusions. Results: Increasing the droplet size of the lipid emulsion was associated with diminished suppression of antral (r = 0.75, P < 0.01) and duodenal (r = 0.80, P < 0.01) pressure waves and with stimulation of isolated (r = -0.72, P < 0.01) and basal (r = -0.83, P < 0.01) pyloric pressures. Increasing the droplet size was also associated with attenuation of the stimulation of plasma triglycerides (r = -0.73, P < 0.001), cholecystokinin (r = -0.73, P < 0.001), and peptide YY (r = -0.83, P < 0.001) as well as with reductions in the suppression of hunger (r = 0.75, P < 0.01) and energy intake (r = 0.66, P < 0.001). Conclusions: The acute effects of intraduodenal fat emulsions on gastrointestinal function and appetite are dependent on fat droplet size. These observations have implications for the design of functional foods to maximize effects on those gut functions that are involved in the suppression of appetite.

Background: The daily energy imbalance gap associated with the current population weight gain in the obesity epidemic is relatively small. However, the substantially higher body weights of populations that have accumulated over several years are associated with a substantially higher total energy expenditure (TEE) and total energy intake (TEI), or energy flux (EnFlux = TEE = TEI). Objective: The objective was to develop an equation relating EnFlux to body weight in adults for estimating the rise in EnFlux associated with the obesity epidemic. Design: Multicenter, cross-sectional data for TEE from doubly labeled water studies in 1399 adults aged 5.9 [+ or -] 18.8 y (mean [+ or -] SD) were analyzed in linear regression models with natural log (In) weight as the dependent variable and In EnFlux as the independent variable, adjusted for height, age, and sex. These equations were compared with those for children and applied to population trends in weight gain. Results: In EnFlux was positively related to In weight ([beta] = 0.71; 95% CI: 0.66, 0.76; [R.sup.2] = 0.52), adjusted for height, age, and sex. This slope was significantly steeper than that previously described for children ([beta] = 0.45; 95% CI: 0.38, 0.51). Conclusions: This relation suggests that substantial increases in TEI have driven the increases in body weight over the past 3 decades. Adults have a higher proportional weight gain than children for the same proportional increase in energy intake, mostly because of a higher fat content of the weight being gained. The obesity epidemic will not be reversed without large reductions in energy intake, increases in physical activity, or both.

Background: Capsinoids from the Capsicum genus of plants are nonpungent capsaicin-related substances with effects on metabolism and body weight in animals. Objectives: Our objectives were to explore the safety and efficacy of capsinoids taken orally (6 mg/d) for weight loss, fat loss, and change in metabolism and to examine whether candidate genes are predictors of capsinoid response. Design: This was a 12-wk, placebo-controlled, double-blind, randomized study. Eligibility criteria included a body mass index (BMI; in kg/[m.sup.2]) of 25-35. Body weight was measured, and dual-energy X-ray absorptiometry, indirect calorimetry (men only), and genotyping were conducted. Results: Forty women and 40 men with a mean ([+ or -] SD) age of 42 [+ or -] 8 y and BMI of 30.4 [+ or -] 2.4 were randomly assigned to a capsinoid or placebo group. Capsinoids were well tolerated. Mean ([+ or -] SD) weight change was 0.9 [+ or -] 3.1 and 0.5 [+ or -] 2.4 kg in the capsinoid and placebo groups, respectively (P = 0.86). There was no significant group difference in total change in adiposity, but abdominal adiposity decreased more (P = 0.049) in the capsinoid group (-1.11 [+ or -] 1.83%) than in the placebo group (-0.18 [+ or -] 1.94%), and this change correlated with the change in body weight (r = 0.46, P < 0.0001). Changes in resting energy expenditure did not differ significantly between groups, but fat oxidation was higher at the end of the study in the capsinoid group (least-squares mean difference: 21.0 mg/min; P = 0.06). Of 13 genetic variants tested, TRPV1 Va1585Ile and UCP2 -866 G/A correlated significantly with change in abdominal adiposity. Conclusions: Treatment with 6 mg/d capsinoids orally appeared to be safe and was associated with abdominal fat loss. Capsinoid ingestion was associated with an increase in fat oxidation that was nearly significant. We identified 2 common genetic variants that may be predictors of therapeutic response.

Background: Twenty-four-hour dietary recalls have been used in large surveys of infant and toddler energy intake, but the accuracy of the method for young children is not well documented. Objective: We aimed to determine the accuracy of infant and toddler energy intakes by a single, telephone-administered, multiple-pass 24-h recall as compared with 3-d weighed food records. Design: A within-subjects design was used in which a 24-h recall and 3-d weighed food records were completed within 2 wk by 157 mothers (56 non-Hispanic white, 51 non-Hispanic black, and 50 Hispanic) of 7-11-mo-old infants or 12-24-mo-old toddlers. Child and caregiver anthropometrics, child eating patterns, and caregiver demographics and social desirability were evaluated as correlates of reporting bias. Results: Intakes based on 3-d weighed food records were within 5% of estimated energy requirements. Compared with the 3-d weighed food records, the 24-h recall overestimated energy intake by 13% among infants (740 [+ or -] 154 and 833 [+ or -] 255 kcal, respectively) and by 29% among toddlers (885 [+ or -] 197 and 1140 [+ or -] 299 kcal, respectively). Eating patterns (ie, frequency and location) did not differ appreciably between methods. Macronutrient and micronutrient intakes were higher by 24-h recall than by 3-d weighed food record. Dairy and grains contributed the most energy to the diet and accounted for 74% and 54% of the overestimation seen in infants and toddlers, respectively. Greater overestimation was associated with a greater number of food items reported by the caregiver and lower child weight-for-length z scores. Conclusions: The use of a single, telephone-administered, multiple-pass 24-h recall may significantly overestimate infant or toddler energy and nutrient intakes because of portion size estimation errors.

Background: Seasonality has been recognized as a key determinant of human energy balance, especially in low-income countries. Objective: The objective was to test the hypothesis that, in rural Bangladesh, different age and sex groups adapt similarly to seasonal changes in energy intake (EI). Design: A prospective study was carried out in 2 rural Bangladeshi villages in the lean and peak seasons. Data on anthropometric measures (weight, height, and midupper arm circumference) and dietary food intake (collected with the use of a 24-h food weighing method) were obtained from all subjects from 304 households. Results: The average EI increased from a least-squares mean ([+ or -] SE) of 7.87 [+ or -] 0.10 MJ * [person.sup.-1] * [d.sup.-1] in the lean season to 9.47 [+ or -] 0.13 MJ * [person.sup.-1] * [d.sup.-1] in the peak season. In children and adolescents aged < 18 y of age, the prevalence of underweight (weight-for-age) was not significantly different (56%) in the 2 seasons. Among adults, a significantly higher prevalence of chronic energy deficiency [body mass index (in kg/[m.sup.2] < 18.5] was observed in the peak season (67%) than in the lean season (61%), despite a higher EI in the peak season. Other determinants of seasonal nutritional status are presented. Conclusions: Seasonal fluctuations in EI were substantial in all age and sex groups. Children and adolescents showed no significant seasonal changes in the prevalence of underweight, which indicated that they adapted to changes in EI. In adults, the season in which EI was high coincided with average weight loss, which indicated that adults did not adapt fully to seasonal fluctuations in EI and that seasonal energy expenditure is probably a major determinant of nutritional status. KEY WORDS Seasonality, anthropometry, underweight, chronic energy deficiency, Bangladesh, children, adolescents, adults, physical activity level

Background: Children have a high resting energy expenditure (REE) relative to their body weight. The decline in REE during growth may be due to changes in body composition or to changes in the metabolic rate of individual organs and tissues. Objectives: The goals were to quantify body-composition components in children at the organ-tissue level in vivo and to determine whether the observed masses 1) account for the elevated REE in children and 2) account, when combined with specific organ-tissue metabolic constants, for children's REE. Design: This was a cross-sectional evaluation of 15 children (aged 9.3 [+ or -] 1.7 y) and 13 young adults (aged 26.0 [+ or -] 1.8 y) with body mass indexes (in kg/[m.sup.2]) < 30. Magnetic resonance imaging-derived in vivo measures of brain, liver, kidney, heart, skeletal muscle, and adipose tissue were acquired. REE was measured by indirect calorimetry ([REE.sub.m]). Previously published organ-tissue metabolic rate constants were used to calculate whole-body REE ([REE.sub.c]). Results: The proportion of adipose-tissue-free mass as liver (3.7 [+ or -]0.5% compared with 3.1 [+ or -] 0.5%; P < 0.01) and brain (6.2 [+ or -] 1.2% compared with 3.3 [+ or -] 0.9%; P < 0.001) was significantly greater in children than in young adults. The addition of brain and liver mass significantly improved the model but did not eliminate the role of age. [REE.sub.c] with published metabolic coefficients underestimated [REE.sub.m] ([REE.sub.c] = 3869 [+ or -] 615 kJ/d; [REE.sub.m] = 5119 + 769 kJ/d; P < 0.001) in children. Conclusion: The decline in REE during growth is likely due to both a decrease in the proportion of some of the more metabolically active organs and tissues and changes in the metabolic rate of individual organs and tissues. KEY WORDS Organ mass, fat-free mass, resting energy expenditure, magnetic resonance imaging, growth, children

Background: Nicotine replacement therapy limits weight gain after smoking cessation. This finding is partly attributable to the thermogenic effect of nicotine, which may be enhanced by caffeine. Objective: We assessed the acute thermogenic effects of chewing gum containing different doses of nicotine and caffeine. Design: This randomized, double-blind, placebo-controlled, crossover study included 12 healthy, normal-weight men (aged 18-45 y). Energy expenditure was measured with indirect calorimetry before and 2.5 h after subjects chewed each of 7 different types of gum containing the following doses of nicotine/caffeine: 0/0, 1/0, 2/0, 1/50, 2/50, 1/100, and 2/100 mg/mg. Results: The thermogenic responses (increases over the response to placebo) were 3.7%, 4.9%, 7.9%, 6.3%, 8.5%, and 9.8%, respectively, for the gums containing 1/0, 2/0, 1/50, 2/50, 1/100, and 2/100 mg nicotine/mg caffeine (P < 0.05 for all). Adding caffeine to 1 and 2 mg nicotine significantly enhanced the thermogenic response, but changing the caffeine dose (from 50 to 100 mg) did not change the thermogenic effect. None of the combinations changed the respiratory quotient compared with placebo, which indicates that glucose and fat oxidation rates were increased to a similar extent. Side effects occurred only with 2 mg nicotine. Conclusions: One milligram of nicotine has a pronounced thermogenic effect, which can be increased by [approximately equal to] 100% by adding 100 mg caffeine. Increasing the nicotine dose to 2 mg does not increase the thermogenic effect but produces side effects in most subjects. Caffeine may be useful in preventing weight gain after smoking cessation if its thermogenic effect can be used to enhance nicotine's effect on long-term energy balance. KEY WORDS Nicotine, caffeine, fatty acid oxidation, carbohydrate oxidation, energy expenditure, respiratory quotient, smoking cessation, weight management, weight control, cigarette smoking

Background: Little is known about the effect of weight change on regional lean body mass (LBM) distribution or on racial differences in resting metabolic rate (RMR). Objective: The study compared total and regional LBM patterns in white and black women after weight loss and regain and assessed the influence of regional LBM on variances in RMR. Design: Eighteen white and 22 black women who did not differ in age, weight, and height were studied 3 times: in the overweight state, after weight reduction to the normal-weight state, and after 1 y without intervention. Total and regional lean and fat masses were assessed by dual-energy X-ray absorptiometry. Results: White and black women did not differ significantly in mean ([+ or -] SD) weight loss (13.4 [+ or -] 3.6 and 12.7 [+ or -] 3.2 kg, respectively) and regain (6.1 [+ or -] 5.5 and 6.4 [+ or -] 5.4 kg, respectively). Black subjects had significantly less trunk LBM and significantly more limb LBM at each time point (P < 0.05). In both races, weight regain was associated with significant increases in limb LBM (P < 0.05) but not in trunk LBM (P = 0.21). RMR, adjusted for total LBM and fat mass, was significantly higher in white women after weight loss (P < 0.01) and regain (P < 0.01). However, no racial difference was found when RMR was adjusted for LBM distribution. Conclusions: In both races, trunk LBM decreased with weight loss and remained lower, despite significant weight regain, which potentially reflected decreased organ mass. Regional LBM distribution explained the racial difference in RMR. KEY WORDS Overweight, obesity, weight loss, body composition, resting metabolic rate, lean body mass, fat mass, regional distribution, African American women

Background: The energy requirements of women have been based on total energy expenditure (TEE) derived from the factorial approach or as multiples of basal metabolic rate (BMR). Objective: This study was designed to reevaluate the energy requirements of healthy, moderately active underweight, normal-weight, and overweight women of reproductive age. Design: The energy requirements of 116 women [n = 13 with a low body mass index (BMI), n = 70 with a normal BMI, and n = 33 with a high BMI] were estimated from TEE measured by the doubly labeled water method. Twenty-four-hour EE and BMR were measured by room respiration calorimetry, activity EE was estimated from nonbasal EE as TEE - BMR, and physical activity level was calculated as TEE/BMR. Body composition was derived from a multicomponent model. Fitness, strength, and physical activity level were assessed, and fasting serum indexes were measured. Results: Energy requirements differed among the low-BMI (8.9 [+ or -] 0.9 MJ/d), normal-BMI (10.1 [+ or -] 1.4 MJ/d), and high-BMI (11.5 [+ or -] 1.9 MJ/d) groups (P = 0.02-0.001, all pairwise comparisons). Major predictors of BMR, 24-h EE, and TEE were weight, height, and body composition; minor predictors were fasting metabolic profile and fitness. Fat-free mass and fat mass accounted for the differences in EE seen between the BMI groups. The mean physical activity level of 1.86 suggested that the multiples of BMR used to estimate energy requirements have been underestimated. Conclusion: Recommended energy intakes for healthy, moderately active women of reproductive age living in industrialized societies should be revised on the basis of TEE. KEY WORDS Energy requirements, total energy expenditure, basal metabolic rate, activity, body composition, doubly labeled water method, women

Background: Estimating energy requirements is a frequent task in clinical studies. Objective: We examined weight patterns of participants enrolled in a clinical trial and evaluated factors that may affect weight stabilization. The Harris-Benedict equation and the FAO/WHO equation, used in conjunction with physical activity levels estimated with the 7-d Physical Activity Recall, were compared for estimating energy expenditure. Design: This was a multicenter, randomized controlled feeding trial with participants of the Dietary Approaches to Stop Hypertension Trial. For 11 wk, the amount of food participants received was adjusted to maintain their body weights as close to their initial weights as possible. Change-point regression techniques were used to identify weight-stable periods. Factors related to achieving weight stabilization were examined with logistic regression. Results: A stable weight was achieved by 86% of the 448 participants during the run-in period and by 78% during the intervention period. Energy intake averaged 11 [+ or -] 2.4 MJ/d (2628 [+ or -] 578 kcal/d), with most participants (n = 270) requiring 9-13 MJ/d (2100-3100 kcal/d). The difference between predicted and observed intakes was highest at high estimated energy intakes, mainly because of high and probably incorrect estimates of the activity factor. Participants with lower energy intakes tended to need less adjustment of their energy intakes to maintain a stable weight than did participants with higher energy intakes. Conclusions: Weight stabilization is not affected by diet composition, sex, race, age, or baseline weight. Either the Harris-Benedict equation or the FAO/WHO equation can be used to estimate energy needs. Activity factors > 1.7 often lead to overestimation of energy needs. KEY WORDS Harris-Benedict equation, FAO/WHO energy equation, stable weight, activity factor, controlled feeding study, clinical trial, clinical study

Background: Little is known about the relation between body composition and energy metabolism in paraplegia. Objective: We investigated the relation between body composition and energy metabolism in healthy paraplegics as compared with able-bodied control subjects. We hypothesized that paraplegics would have lower fat-free mass (FFM), body cell mass (BCM), resting metabolic rate (RMR), and thermic effect of feeding (TEF). Design: This cross-sectional study included 34 control subjects and 28 paraplegics (mean age: 29.1 [+ or -] 7.6 and 33.9 [+ or -] 9.2 y, respectively) with body mass indexes (in kg/[m.sup.2]) of 23.5 [+ or -] 1.8 and 24.3 [+ or -] 6.0, respectively. We measured RMR and TEF with indirect calorimetry, total body water with deuterium dilution, and extracellular water with corrected bromide space. We calculated FFM (total body water/0.732) and BCM [(total body water--extracellular water)/0.732)]. Results: FFM was higher in control subjects than in paraplegics (77.2 [+ or -] 7.2% and 69.2 [+ or -] 8.7%, respectively; P = 0.0002), as were BCM (47.4 [+ or -] 6.7% and 35.9 [+ or -] 8.1%, respectively; P < 0.0001) and RMR (7016 [+ or -] 935 and 6159 [+ or -] 954 kJ/d, respectively; P = 0.0007). FFM was the single best predictor of RMR in both groups ([r.sup.2] = 0.83 for control subjects and 0.70 for paraplegics, P < 0.0001 for both). RMR adjusted for FFM did not differ significantly between control subjects and paraplegics (6670 [+ or -] 504 and 6588 [+ or -] 501 kJ/d, respectively). TEF also did not differ significantly between control subjects and paraplegics (6.25 [+ or -] 2.2% and 5.53 [+ or -] 1.8% of energy intake, respectively). Conclusions: FFM, BCM, and RMR, but not obligatory TEF, are lower in paraplegics than in control subjects. RMR does not differ between control and paraplegic subjects after adjustment for FFM, indicating similar metabolic activity in the fat-free compartment of the body. KEY WORDS Paraplegia, disability, spinal cord injury, body composition, fat-free mass, resting metabolic rate, thermic effect of feeding

Background: On the basis of observations in rodents, leptin is thought to play a key role in the regulation of energy expenditure and food intake, but less is known of its influence on ingestive behavior and energy balance in humans. Objective: We examined the effect in women of a chronic energy deficit on plasma leptin concentrations and self-reported appetite and explored possible relations between leptin and appetite sensations. Design: Twelve healthy women (body mass index, in kg/[m.sup.2]: 23-37) participated in a metabolic ward study in which 3 wk of neutral energy balance was followed by 12 wk of energy deficit (energy intake reduced by 2 MJ/d and energy expenditure increased by 0.8 MJ/d). Body weight and composition were monitored, fasting leptin concentrations were measured 4 times, and feelings of hunger, fullness, desire to eat, and prospective consumption were monitored hourly throughout the day on 7 selected days. Results: Adiposity-adjusted leptin decreased by 54% after 1 wk of a moderate energy deficit and remained low after 6 and 12 wk. Leptin was associated with self-reported hunger, desire to eat, and prospective consumption (range of r: -0.6 to -0.7, P [is less than] 0.01). The greatest hunger increase coincided with the largest percentage drop in circulating leptin and the lowest final leptin concentration. The relation between leptin and hunger was not influenced by amount of weight or body fat loss. Conclusions: These findings support the idea that leptin is a physiologic regulator of hunger during energy deficits in humans; the role of leptin in the long-term regulation of food intake warrants further study. Am J Clin Nutr 1998;68:794-801.

The effect of overfeeding on energy expenditure was investigated in 23 young men subjected to a 353-MJ energy intake surplus over 100 d. The major part of this excess (222 MJ) was stored as body energy. The increase in energy cost of weight maintenance amounted to 52 MJ and was proportional to body weight gain. When it was added to the obligatory cost of fat and fat-free mass gains, the overall increase in energy expenditure amounted to a mean of 100 MJ. Four months after overfeeding, subjects had lost 82%, 74%, and 100% of the overfeeding gain in body weight, fat mass, and fat-free mass, respectively. We conclude that 1) in response to overfeeding, two-thirds of the excess energy intake is stored as body energy; 2) overfeeding induces an increase in energy cost of weight maintenance proportional to body weight gain, and 3) preoverfeeding energy balance tends to be restored when nonobese individuals return to their normal daily-life habits. Am J Clin Nutr 1992;56:857-62.

Dietary responses to dilution or supplementation of the energy value and macronutrient content of foods are poorly characterized in humans. After a 1-wk baseline, 16 free-living, normal-weight adults were provided midday meals systematically varying in energy, fat, and carbohydrate contents for 5-d periods. Their compensatory free-feeding intake was monitored through diet records. In response to energy dilution by carbohydrate or fat, mean daily energy intake was 88% and 97% of baseline, respectively. Responses to the energy surfeit led to intakes 104% and 116% of baseline, respectively. However, the absolute magnitude of the carbohydrate supplement challenge was small. Adjustments of macronutrient-specific intake during the high-carbohydrate, low-carbohydrate, high-fat, and low-fat meal periods were 134%, 91%, 165%, and 95% of baseline, respectively. Although these group findings indicate that defense against covert dilution of the energy, fat, or carbohydrate contents of a meal is stronger than that to supplementation, individual responses were highly variable. Am J Clin Nutr 1992; 56:36-43.

In people who maintain a stable weight, the amount of calories in the food they eat is equal to the energy they expend. Generally, one would assume that when people eat more food than normal, their weight would rise in proportion to the extent of hyperphagia (overeating). However, observations since 1881 have found that the rate of weight gain per degree of overeating decreases as the duration of hyperphagia increases. The excessive ingested calories which do not end up as weight gain apparently are dissipated as heat, and the various types of heat dissipation are referred to as facultative (noncompulsory) thermogenesis. A method of analysis of the body's energy handling is described in this article. Energy is considered to be stored in only two compartments, the fat store and the fat-free mass (FFM), which consists of the body cell mass, extracellular water, and extracellular fat-free solids. In addition, the storage and usage of energy is not static, but rather changes in response to environment, food usage, and time, and so a dynamic analysis of energy balance is used. Finally, the analysis only concerns itself with obligatory, compulsory, energy uses, including resting metabolic rate (RMR), thermic effect of food (TEF), and thermic effect of exercise (TEE). The analysis shows that for either semi-starvation or overeating, RMR is related to FFM and to a factor related to the imbalance between food intake and energy need. During overeating, most of the excess energy goes into the fat store, but with increasing duration of overeating, greater amounts are diverted to FFM. The weight gain per excess caloric intake decreases over time, as both FFM and the fat store cannot grow infinitely, but rather are ultimately limited. This means that facultative thermogenesis becomes increasingly important in taking care of excess calories as the two compartments approach their limits. Further research on long-term hyperphagia and facultative thermogenic processes, especially for periods over 42 days, is needed. (Consumer Summary produced by Reliance Medical Information, Inc.)

Both physical activity and diet stimulate processes that, over time, alter the morphologic composition and biochemical function of the body. Physical activity provides stimuli that promote very specific and varied adaptations according to the type, intensity, and duration of exercise performed. There is further interest in the extent to which diet or supplementation can enhance the positive stimuli. Prolonged walking at low intensity presents little metabolic, hormonal, or cardiovascular stress, and the greatest perturbation from rest appears to be from increased fat oxidation and plasma free fatty acid mobilization resulting from a combination of increased lipolysis and decreased reesterification. More intense jogging or running largely stimulates increased oxidation of glycogen and triacylglycerol, both of which are stored directly within the muscle fibers. Furthermore, these intramuscular stores of carbohydrate and fat appear to be the primary substrates for the enhanced oxidative and performance ability derived from endurance training-induced increases in muscle mitochondrial density. Weight-lifting that produces fatigue in brief periods (ie, in 15-90 s and after 15 repetitive contractions) elicits a high degree of motor unit recruitment and muscle fiber stimulation. This is a remarkably potent stimulus for altering protein synthesis in muscle and increasing neuromuscular function. The metabolic stress of physical activity can be measured by substrate turnover and depletion, cardiovascular response, hormonal perturbation, accumulation of metabolites, or even the extent to which the synthesis and degradation of specific proteins are altered, either acutely or by chronic exercise training. Am J Clin Nutr 2000;72(suppl):512S-20S. KEY WORDS Exercise, physical activity, exertion, nutrition, carbohydrate, triacylglycerol, protein synthesis, hormone, muscle