Cognitive dietary restraint, disinhibition, and hunger are associated with 24-h energy expenditure.

BACKGROUND: Higher energy expenditure (EE) is associated with greater food intake, possibly because the human body senses EE and modifies eating behaviors to regulate food intake and ultimately achieve energy balance. As eating behaviors are also influenced by social and cultural factors, any association between EE and eating behavior may differ between ethnicities and sexes. OBJECTIVE: To assess relationships between EE and eating behavior constructs of the Three-Factor Eating Questionnaire (TFEQ). SUBJECTS/METHODS: In all, 307 healthy adults (201 M/106 F, 160 Native Americans) completed the TFEQ and had measures of 24-h EE in a whole-room calorimeter during energy balance. Body composition was assessed by DXA. RESULTS: On average, adjusted 24-h EE was lower (ß = -229 kcal/day, CI: -309 to -148, p < 0.001) but cognitive restraint (Δ = + 1.5; CI: 0.5 to 2.5, p = 0.003) and disinhibition (Δ = + 2.1, CI: 1.3 to 2.8, p < 0.001) scores were higher in women compared with men. In Native Americans, adjusted 24-h EE (ß = + 94 kcal/day, CI: 48 to 139, p < 0.001) and disinhibition scores (Δ = + 1.0, CI: 0.1 to 2.0, p = 0.003) were higher compared with other ethnicities. Higher 24-h EE associated with lower cognitive restraint in women (ρ = -0.20, p = 0.04), but not men (p = 0.71; interaction term p = 0.01) with no ethnic differences. Greater 24-h EE associated with higher disinhibition (ρ = 0.20, p = 0.001) and hunger cues (ρ = 0.16, p = 0.004) with no gender differences. These associations were primarily present in non-Native Americans (ρ = 0.23, p = 0.006 and ρ = 0.25, p = 0.003) but not observed in Native Americans (both p > 0.40). CONCLUSIONS: Higher EE is associated with psychological constructs of eating behaviors that favors overeating including lower cognitive restraint, higher dietary disinhibition, and greater susceptibility to hungers cues, supporting the existence of energy-sensing mechanisms influencing human eating behavior. These associations were observed in ethnicities other than Native Americans, possibly explaining the contradictory relationships reported between EE and weight change in different ethnic groups. We propose that increased EE may alter eating behaviors, potentially leading to uncontrolled overeating and weight gain.

Early results of a surgeon-led, perioperative surgical home.

BACKGROUND: The Perioperative Surgical Home is a novel care model designed to provide patient-centered, high-quality surgical care. In 2013, we implemented POSH, a pilot Peri-Operative Surgical Home at Phoenix Indian Medical Center (PIMC), an Indian Health Service hospital, as a quality improvement project. After 2 y, we sought to quantify the impact of POSH on the quality of surgical care at PIMC. MATERIALS AND METHODS: We conducted a retrospective review of 33 surgical patients who underwent surgery at PIMC through the POSH process between 2013 and 2015 matched to 64 historical controls with similar operations. Study patients underwent surgery via the POSH treatment process. Primary outcomes were composite measures of (1) care standards and (2) care goals. Success was defined as meeting seven of nine care standards and six of eight care goals. RESULTS AND DISCUSSION: The mean number of care standards met was 8.1 ± 1.0 versus 4.2 ± 1.4 (P < 0.001) and the mean number of care goals met was 6.7 ± 0.8 versus 6.1 ± 1.1 (P = 0.005) for POSH patients and historical controls, respectively. Patients participating in the POSH model were 8.6 (95% confidence interval: 3.5-22.3) and 1.5 (95% confidence interval: 1.2-1.9) times more likely to meet the minimum number of care standards and goals, respectively. Fourteen of the study patients (42%) would not have been offered surgery at PIMC before POSH due to elevated surgical risk. CONCLUSIONS: POSH may have improved quality of surgical care at PIMC while expanding services to more complex patients. POSH may present an opportunity for improved surgical quality in resource-constrained environments.

T-cell receptor repertoire variation may be associated with type 2 diabetes mellitus in humans.

BACKGROUND: Recent work in Pima Indians, a population with high rates of obesity and type 2 diabetes mellitus (T2DM), demonstrated that human leukocyte antigen haplotype DRB1*02 carriers have an increased acute insulin response and decreased risk for the development of T2DM, implicating loss of self-tolerance in the pathogenesis of T2DM. Advances in genomic sequencing have made T-cell receptor repertoire analysis a practical mode of investigation. METHODS: High-throughput sequencing of T-cell receptor complementarity-determining region 3 was carried out in male Pima Indians with normal glucose regulation (n = 11; age = 31 ± 8 years; %fat = 30.2 ± 8.7%) and the protective DRB1*02 haplotype versus those with T2DM without DRB1*02 (n = 7; age = 34 ± 8 years; %fat = 31.2 ± 4.7%). Findings were partially replicated in another cohort by assessing the predictive ability of T-cell receptor variation on risk of T2DM in Pima Indian men (n = 27; age = 28.9 ± 7.1 years; %fat = 28.8 ± 7.1%) and women (n = 20; age = 29 ± 7.0 years; %fat = 37.1 ± 6.8%) with baseline normal glucose regulation but without the protective haplotype who were invited to follow-up examinations as frequently as every 2 years where diabetes status was assessed by a 75-g oral glucose tolerance test. Of these subjects, 13 developed diabetes. RESULTS: T-cell receptor complementarity-determining region 3 length was shorter in those with T2DM, and a one-nucleotide decrease in complementarity-determining region 3 length was associated with a nearly threefold increase in risk for future diabetes. The frequency of one variable gene, TRBV7-8, was higher in those with T2DM. A 1% increase in TRBV7-8 frequency was associated with a greater than threefold increase in diabetes risk. CONCLUSIONS: These results indicate that T-cell autoimmunity may be an important component in progression to T2DM in Pima Indians.

Increased 24-hour ad libitum food intake is associated with lower plasma irisin concentrations the following morning in adult humans.

BACKGROUND: The relationship between food intake and irisin concentrations in humans is unclear. OBJECTIVES: To determine whether the previous day's intake impacts fasting plasma irisin concentrations, or whether fasting irisin concentrations associate with subsequent ad libitum food intake. METHODS: Sixty-six nondiabetic adults (42 men) were admitted for a study of the determinants of energy intake. After 6 days of a weight maintaining diet, ad libitum energy intake over 3 days was assessed using a vending machine paradigm. Fasting plasma irisin concentrations were measured on the morning of the second day of the vending period. RESULTS: There were no correlations between irisin and demographic or anthropometric parameters. On day 1, subjects consumed 144 ± 52% of weight maintaining energy needs. Every additional 500 kcal consumed on day 1 associated with a 3.4% lower irisin concentration the following morning (95% CI -6.2, -0.4%, p = 0.01; adjusted for age, sex and race). If energy intake was expressed as a percentage of weight maintaining energy needs, every 10% increase associated with a 1.9% lower irisin concentration (95% CI -3.7, -0.1%; adjusted p = 0.02). A 100 kcal increase in carbohydrate or fat consumption associated with a 1.3% (95% CI -2.5, -0.1%, p = 0.01) and a 0.6% (95% CI -1.1, -0.0%, p = 0.02) lower irisin concentration, respectively. There was no association between fasting irisin concentrations and subsequent energy intake on day 2 (r = 0.19, p = 0.1). CONCLUSIONS: Higher ad libitum 24 h energy intake was associated with lower fasting irisin concentrations the following morning, but fasting irisin concentrations did not predict subsequent energy intake. The decrease in irisin concentrations with increased energy intake is consistent with the detrimental metabolic effects of overeating.

Common genetic variation in the glucokinase gene (GCK) is associated with type 2 diabetes and rates of carbohydrate oxidation and energy expenditure.

AIMS/HYPOTHESIS: Glucokinase (GCK) plays a role in glucose metabolism and glucose-stimulated insulin secretion. Rare mutations in GCK cause MODY. We investigated whether common variation (minor allele frequency ≥0.01) in GCK is associated with metabolic traits and type 2 diabetes. METHODS: Four exonic single-nucleotide polymorphisms (SNPs) and three SNPs predicted to cause loss of promoter function were identified in whole-genome sequence data from 234 Pima Indians. These seven tag SNPs and rs4607517, a type 2 diabetes variant established in other studies, were analysed in 415 full-heritage non-diabetic Pima Indians characterised for metabolic traits, and 7,667 American Indians who had data on type 2 diabetes and BMI. RESULTS: A novel 3' untranslated region (3'UTR) SNP, chr7:44184184-G/A, was associated with the rate of carbohydrate oxidation post-absorptively (ß = 0.22 mg [kg estimated metabolic body size (EMBS)](-1) min(-1), p = 0.005) and during a hyperinsulinaemic-euglycaemic clamp (ß = 0.24 mg [kg EMBS](-1) min(-1), p = 0.0002), the rate of carbohydrate oxidation in a respiratory chamber (ß = 311 kJ/day, p = 0.03) and 24 h energy expenditure, which was attributable to the thermic effect of food (ß = 520 kJ/day, p = 3.39 × 10(-6)). This 3'UTR SNP was also associated with diabetes (OR 1.36, 95% CI 1.11, 1.65, p = 0.002), where the A allele (allele frequency 0.05) was associated with a lower rate of carbohydrate oxidation, lower 24 h energy expenditure and higher risk for diabetes. In a Cox proportional hazards model, a rate of insulin-stimulated carbohydrate oxidation lower than the mean rate at baseline predicted a higher risk for developing diabetes than for those above the mean (hazard rate ratio 2.2, 95% CI 1.3, 3.6, p = 0.002). CONCLUSIONS/INTERPRETATION: Common variation in GCK influences the rate of carbohydrate oxidation, 24 h energy expenditure and diabetes risk in Pima Indians.

Common genetic variation in and near the melanocortin 4 receptor gene (MC4R) is associated with body mass index in American Indian adults and children.

Six rare functional coding mutations were previously identified in melanocortin 4 receptor (MC4R) in 6,760 American Indians. Individuals heterozygous for one of these mutations become obese while young. We now investigate whether common non-coding variation near MC4R also contributes to obesity. Fifty-six tag single-nucleotide polymorphisms (SNPs) were genotyped in 3,229 full-heritage Pima Indians, and nine of these SNPs which showed evidence for association were genotyped in additional 3,852 mixed-heritage American Indians. Associations of SNPs with maximum body mass index (BMI) in adulthood (n = 5,918), BMI z score in childhood (n = 5,350), percent body fat (n = 864), energy expenditure (n = 358) and ad libitum food intake (n = 178) were assessed. Conditional analyses demonstrated that SNPs, rs74861148 and rs483125, were independently associated with BMI in adulthood (ß = 0.68 kg/m(2) per risk allele, p = 5 × 10(-5); ß = 0.58 kg/m(2), p = 0.002, respectively) and BMI z score in childhood (ß = 0.05, p = 0.02; ß = 0.07, p = 0.01, respectively). One haplotype (frequency = 0.35) of the G allele at rs74861148 and the A allele at rs483125 provided the strongest evidence for association with adult BMI (ß = 0.89 kg/m(2), p = 5.5 × 10(-7)), and was also associated with childhood BMI z score (ß = 0.08, p = 0.001). In addition, a promoter SNP rs11872992 was nominally associated with adult BMI (ß = 0.61 kg/m(2), p = 0.05) and childhood BMI z score (ß = 0.11, p = 0.01), where the risk allele also modestly decreased transcription in vitro by 12 % (p = 0.005). This risk allele was further associated with increased percent body fat (ß = 2.2 %, p = 0.002), increased food intake (ß = 676 kcal/day, p = 0.007) and decreased energy expenditure (ß = -53.4 kcal/day, p = 0.054). Common and rare variation in MC4R contributes to obesity in American Indians.

Perseveration augments the effects of cognitive restraint on ad libitum food intake in adults seeking weight loss.

As executive function may influence eating behaviors, our aim was to determine whether measures of executive function predict ad libitum food intake in subjects seeking weight loss. 78 obese, healthy individuals (40 female/38 male; age 36 ± 10 y; BMI 37.8 ± 7.2 kg/m(2)) completed the Iowa Gambling Task to evaluate decision making, the Stroop Word Color Task to assess attention, the Wisconsin Card Sorting Task to measure perseveration, and the Three Factor Eating Questionnaire to measure disinhibition and cognitive restraint. Ad libitum energy intake over 3-days was then collected using a validated vending paradigm. When expressed as a percentage of an individual's weight maintaining energy needs (%WMEN), intake correlated positively with perseveration (r=0.24, p=0.03) and negatively with restraint (r=-0.51, p<0.0001). In a regression model of %WMEN (r(2)=0.59, p<0.0001), an interaction between perseveration and restraint was observed (p=0.05). Increased perseveration intensified the effect of restraint such that subjects with both high restraint and perseveration ate the least (median (IQR)=70 (62, 94) %WMEN), while those with low restraint and high perseveration ate the most (130 (102, 153) %WMEN). Subjects with low perseveration and high versus low restraint ate a median of 84 (70, 86) and 112 (98, 133) %WMEN, respectively. The effects of perseveration on food intake are conditional on restraint, and may contribute to extremes of dietary intake in some individuals.

Temozolomide (Temodar®) and capecitabine (Xeloda®) treatment of an aggressive corticotroph pituitary tumor.

Only rarely do corticotroph pituitary tumors become invasive leading to symptoms caused by compression of cranial nerves and other local structures. When aggressive pituitary neuroendocrine tumors do develop, conventional treatment options are of limited success. A 50-year-old man developed a giant invasive corticotroph pituitary tumor 2 years after initial presentation. His tumor and symptoms failed to respond to maximal surgical, radio-surgical, radiation and medical therapy and a bilateral adrenalectomy was done. He subsequently developed rapid growth of his tumor leading to multiple cranial nerve deficits. He was administered salvage chemotherapy with capecitabine and temozolomide (CAPTEM), a novel oral chemotherapy regimen developed at our institution for treatment of neuroendocrine tumors. After two cycles of CAPTEM, his tumor markedly decreased in size and ACTH levels fell by almost 90%. Despite further decreases in ACTH levels, his tumor recurred after 5 months with increased avidity on PET scan suggesting a transformation to a more aggressive phenotype. Temozolomide had been reported to be effective against other pituitary tumors and this case adds to this literature demonstrating its use along with capecitabine (CAPTEM) against a corticotroph tumor. Further evaluation of the CAPTEM regimen in patients with pituitary neuroendocrine tumors which fail to respond to classic treatments is warranted.

Core body temperature, energy expenditure, and epinephrine during fasting, eucaloric feeding, and overfeeding in healthy adult men: evidence for a ceiling effect for human thermogenic response to diet.

BACKGROUND: In homeothermic animals, approximately 50% of daily energy expenditure (EE) is spent to maintain a consistent core body temperature (CBT). In humans, little is known about CBT responses to feeding and overfeeding and their relationship to diet-related changes in EE. OBJECTIVE: To study the effects of feeding and overfeeding on CBT and its association with diet-induced thermogenesis (DIT). DESIGN: Fifty-three healthy men with normal glucose regulation and a wide range of body composition (mean ±â€¯SD, body fat: 25 ±â€¯8%, range: 7-43%) had 24-h EE assessed during fasting in a whole-room indirect calorimeter with concomitant CBT measurement by ingestible capsules and 24-h urinary collection for catecholamine measurements. Changes in 24-h EE (DIT) and CBT compared to fasting were assessed during three normal-protein (20%) diets using a cross-over design: one eucaloric diet (EBL, 50% carbohydrate, n = 37) and two overfeeding diets with 200% energy requirements: a high-fat (FNP, 60% fat, n = 25) and a high-carbohydrate (CNP; 75% carbohydrate, n = 24) diet. RESULTS: The average 24-h CBT (avgCBT) during fasting was 36.81 ±â€¯0.14 °C (inter-individual CV = 0.4%) and positively correlated with 24-h urinary epinephrine (r = 0.61, p < 0.001), but not with body composition measures (p > 0.05). AvgCBT increased during EBL (Δ = 0.06 ±â€¯0.11 °C, p = 0.002), FNP (Δ = 0.13 ±â€¯0.14 °C, p < 0.001), and CNP (Δ = 0.19 ±â€¯0.13 °C, p < 0.001) and associated with increased DIT during EBL (r = 0.43, p = 0.01, ß = 31 kcal/day/0.1 °C) and FNP (r = 0.60, p = 0.002, ß = 43 kcal/day/0.1 °C), but not CNP (p = 0.47). A ceiling effect for the increase in CBT, but not in DIT, was observed during feeding and, particularly, overfeeding. CONCLUSIONS: CBT increases with feeding and is moderately associated with DIT to a different degree depending on the macronutrient composition of the overfeeding diet. There is a ceiling effect such that individuals with a higher CBT during fasting have limited capacity to increase CBT with feeding. Because of body thermoregulatory mechanisms that maintain a constant CBT, these results indicate that CBT has a limited role in the inter-individual variability in DIT.

Cycling Efficiency During Incremental Cycle Ergometry After 24 Hours of Overfeeding or Fasting.

OBJECTIVE: The objective of this study was to determine whether net cycling efficiency (NET) is altered by 24-hour fasting or overfeeding and whether it correlates with dietary-related energy expenditure (EE) and future weight change. METHODS: In a crossover design, healthy subjects fasted or were overfed for 24 hours while in a whole-room calorimeter using five diets with doubled energy needs: standard, high-carbohydrate (75%), high-fat (60%), high-protein (30%), and low-protein (3%) diets. Graded cycling exercise at low power outputs (10-25-50 W) was performed the day before and after each dietary intervention. RESULTS: NET did not change following any dietary intervention (all P > 0.05 vs. 0). Individual changes in NET did not correlate with EE responses to dietary interventions. However, the change in NET after low-protein overfeeding was inversely correlated with baseline body fat (r = -0.60, P = 0.01); that is, NET increased in lean but decreased in overweight subjects (Δ = 0.010 ± 0.010 vs. -0.013 ± 0.009, P = 0.0003). Increased NET following the low-protein diet was associated with weight gain after 6 months (r = 0.60, P = 0.05). CONCLUSIONS: Despite no substantial effect of acute overfeeding or fasting on NET, the change in NET following low-protein overfeeding depends on adiposity and may influence weight change, suggesting that increased efficiency in a setting of protein scarcity is an adaptive response that may ultimately lead to weight gain.

Exenatide has a pronounced effect on energy intake but not energy expenditure in non-diabetic subjects with obesity: A randomized, double-blind, placebo-controlled trial.

AIMS: Exenatide is a glucagon-like peptide 1 (GLP-1) mimetic which induces weight loss predominantly, it is presumed, via decreased food intake. However, circulating GLP-1 is also a determinant of energy expenditure. We sought to quantify the effect of exenatide on energy expenditure (EE) and energy intake. MATERIALS AND METHODS: In this single-center, randomized double-blind placebo controlled trial, we randomized 80 healthy, non-diabetic volunteers with obesity (46 women, age: 34.4 ±â€¯8.7 y, body fat by DXA: 44.2 ±â€¯7.8%) to subcutaneous exenatide 10 µg twice daily or placebo. Subjects were admitted to our clinical research unit for measurement of 24 h-EE in a whole-room indirect calorimeter and ad libitum food intake using an automated vending machine paradigm before and after randomization. Furthermore, energy expenditure and ad libitum food intake measures were repeated at 24-week after readmission for 7-day inpatient stay. Body weight was obtained weekly for up to 5 weeks and was recorded at each monthly follow up visit up to 24 weeks. RESULTS: Prior to randomization, participants over ate during the 3-day vending machine period in the whole study group (114.6 ±â€¯35.2%), expressed as percentage of weight maintaining energy needs (WMEN) with those who were eventually randomized to exenatide overeating more (121.6 ±â€¯37.7%) compared to placebo group (107.6 ±â€¯31.5%). In the exenatide group, ad libitum absolute energy intake decreased by 1016.1 ±â€¯724.5 kcal/day (95% CI: -1250.9 to -781.2) versus a 245.1 ±â€¯710.5 kcal/day (95% CI: -475.4 to -14.7) decrease in placebo (Δ = -624.8 Kcal/day, p < 0.0001) whereas the reduction in ad libitum caloric intake relative to WMEN was a more modest 366.8 ±â€¯752.1 kcal/day (95% CI: -614.0 to -119.6) decrease compared to 8.0 ±â€¯860.1 kcal/day (95% CI: -286.8 to 270.8) reduction in placebo (Δ = -382.3 Kcal/day, p = 0.03). The decrease was uniform across all macronutrients groups. No differences in 24hEE or substrate oxidation rates were found. In the exenatide group, body weight decreased more over the 5 weeks (ß = -0.039 kg/week, p = 0.02) and was lower compared to placebo at the end of fifth week (-1.48 ±â€¯0.77 kg; 95% CI: -3.02 to 0.05, p = 0.06). At the 24-week follow up, there was no difference in energy intake between exenatide group and placebo group and the treatment group decreased 24-h EE more compared to placebo (ß = -160.6 Kcal/day, 95% CI: -307.6 to 13.6, p = 0.03) compared to their pre-randomization measurement. However, this reduction was not present after adjustment for changes in FM and FFM (ß = -87 kcal/day, p = 0.14). No difference was observed in body weight (Δ = -1.72 kg, 95% CI: -5.77 to 2.30, p = 0.39) in exenatide versus placebo over 24 weeks. CONCLUSION: Compared with placebo, exenatide decreased early ad libitum energy intake but did not change 24 h-EE. However, the reduction was more modest in relative versus absolute terms (i.e. below that needed for WMEN). Thus, although rate of weight change was greater in the exenatide treated subjects at 5 weeks, the absolute difference in weight was not significant. These findings indicate that although exenatide reduces food intake, it may be more beneficial in blunting overeating and thus may serve to more prevent weight regain following initial weight loss.

Energy Expenditure and Hormone Responses in Humans After Overeating High-Fructose Corn Syrup Versus Whole-Wheat Foods.

OBJECTIVE: This study sought to understand how the dietary source of carbohydrates, either high-fructose corn syrup (HFCS) or complex carbohydrates, affects energy expenditure (EE) measures, appetitive sensations, and hormones during 24 hours of overfeeding. METHODS: Seventeen healthy participants with normal glucose regulation had 24-hour EE measures and fasting blood and 24-hour urine collection during four different 1-day diets, including an energy-balanced diet, fasting, and two 75% carbohydrate diets (5% fat) given at 200% of energy requirements with either HFCS or whole-wheat foods as the carbohydrate source. In eight volunteers, hunger was assessed with visual analog scales the morning after the diets. RESULTS: Compared with energy balance, 24-hour EE increased 12.8% ± 6.9% with carbohydrate overfeeding (P < 0.0001). No differences in 24-hour EE or macronutrient utilization were observed between the two high-carbohydrate diets; however, sleeping metabolic rate was higher after the HFCS diet (Δ = 35 ± 48 kcal [146 ± 200 kJ]; P = 0.01). Insulin, ghrelin, and triglycerides increased the morning after both overfeeding diets. Urinary cortisol concentrations (82.8 ± 35.9 vs. 107.6 ± 46.9 nmol/24 h; P = 0.01) and morning-after hunger scores (Δ = 2.4 ± 2.0 cm; P = 0.01) were higher with HFCS overfeeding. CONCLUSIONS: The dietary carbohydrate source while overeating did not affect 24-hour EE, but HFCS overconsumption may predispose individuals to further overeating due to increased glucocorticoid release and increased hunger the following morning.

Norepinephrine and T4 Are Predictors of Fat Mass Gain in Humans With Cold-Induced Brown Adipose Tissue Activation.

Context: In healthy adults with detectable cold-induced brown adipose tissue activation (CIBA), the relationships between sympathetic nervous system (SNS) or thyroid activity during energy balance (EBL) with CIBA and body composition change are undetermined. Objective: To investigate the relationships between CIBA and thermoneutral catecholamines and thyroid hormones measured during EBL and to determine if CIBA, catecholamines, or thyroid hormones predict body composition changes. Design, Setting, Participants, and Interventions: Twelve healthy volunteers (seven male and five female) with positive CIBA [>2 standardized uptake value (g/mL)] had 24-hour energy expenditure (24hEE) assessed during EBL via whole-room indirect calorimetry while residing on a clinical research unit. Positron emission tomography/computed tomography scans were performed after exposure to 16°C for 2 hours to quantify CIBA. Main Outcome Measures: CIBA, 24hEE during EBL, and thermoneutrality with concomitant measurement of urinary catecholamines and plasma free T3 and free T4. Body composition at baseline and 6 months by dual-energy X-ray absorptiometry. Results: Lower urinary norepinephrine and free T4 were associated with higher CIBA (r = -0.65, P = 0.03; and r = -0.75, P < 0.01, respectively), but CIBA was not associated with 24hEE at thermoneutrality (P = 0.77). Lower CIBA (ß = -3.5 kg/standardized uptake value; P < 0.01) predicted fat mass gain, whereas higher urinary norepinephrine and free T4 predicted future fat mass gain at 6 months (ß = 3.0 kg per twofold difference in norepinephrine, P = 0.03; and ß = 1.2 kg per 0.1-ng/dL difference in free T4, P = 0.03, respectively). Conclusion: Lower SNS and free thyroid measurements at baseline indicate a greater capacity for CIBA, which may be predictive against fat mass gain.

The Consistency in Macronutrient Oxidation and the Role for Epinephrine in the Response to Fasting and Overfeeding.

Context: In humans, dietary vs intraindividual determinants of macronutrient oxidation preference and the role of the sympathetic nervous system (SNS) during short-term overfeeding and fasting are unclear. Objective: To understand the influence on metabolic changes of diet and SNS during 24 hours of overfeeding. Design, Setting, Participants, and Interventions: While residing on a clinical research unit, 64 participants with normal glucose regulation were assessed during energy balance, fasting, and four 24-hour overfeeding diets, given in random order. The overfeeding diets contained 200% of energy requirements and varied macronutrient proportions: (1) standard (50% carbohydrate, 20% protein, and 30% fat); (2) 75% carbohydrate; (3) 60% fat; and (4) 3% protein. Main Outcome Measures: Twenty-four-hour energy expenditure (EE) and macronutrient oxidation rates were measured in an indirect calorimeter during the dietary interventions, with concomitant measurement of urinary catecholamines and free cortisol. Results: EE decreased with fasting (-7.7% ± 4.8%; P < 0.0001) and increased with overfeeding. The smallest increase occurred during consumption of the diet with 3% protein (2.7% ± 4.5%; P = 0.001) and the greatest during the diet with 75% carbohydrate (13.8 ± 5.7%; P < 0.0001). Approximately 60% of macronutrient oxidation was determined by diet and 20% by intrinsic factors (P < 0.0001). Only urinary epinephrine differed between fasting and overfeeding diets (Δ = 2.25 ± 2.9 µg/24h; P < 0.0001). During fasting, higher urinary epinephrine concentrations correlated with smaller reductions in EE (ρ = 0.34; P = 0.01). Conclusions: Independent from dietary macronutrient proportions, there is a strong individual contribution to fuel preference that remains consistent across diets. Higher urinary epinephrine levels may reflect the importance of epinephrine in maintaining EE during fasting.

Perceived stress and anhedonia predict short-and long-term weight change, respectively, in healthy adults.

OBJECTIVE: Perceived stress; emotional eating; anhedonia; depression and dietary restraint, hunger, and disinhibition have been studied as risk factors for obesity. However, the majority of studies have been cross-sectional and the directionality of these relationships remains unclear. In this longitudinal study, we assess their impact on future weight change. METHODS: Psychological predictors of weight change in short- (6month) and long-term (>1year) periods were studied in 65 lean and obese individuals in two cohorts. Subjects participated in studies of food intake and metabolism that did not include any type of medication or weight loss interventions. They completed psychological questionnaires at baseline and weight change was monitored at follow-up visits. RESULTS: At six months, perceived stress predicted weight gain (r(2)=0.23, P=0.02). There was a significant interaction (r(2)=.38, P=0.009) between perceived stress and positive emotional eating, such that higher scores in both predicted greater weight gain, while those with low stress but high emotional eating scores lost weight. For long-term, higher anhedonia scores predicted weight gain (r(2)=0.24, P=0.04). Depression moderated these effects such that higher scores in both predicted weight gain but higher depression and lower anhedonia scores predicted weight loss. CONCLUSION: There are different behavioral determinants for short- and long-term weight change. Targeting perceived stress may help with short-term weight loss while depression and anhedonia may be better targets for long-term weight regulation.

Non-hematopoietic effects of endogenous erythropoietin on lean mass and body weight regulation.

OBJECTIVE: To investigate the concurrent relationships between human plasma erythropoietin concentrations and energy expenditure (EE), body composition, plasma leptin concentrations, and associations with weight change. METHODS: Plasma to measure erythropoietin and leptin; data for body composition; 24-h EE measured in a whole-room calorimeter; and 75 g oral glucose tolerance testing were available from 109 full-heritage Pima Indians (55% male) from a larger study designed to understand the causes of obesity. Seventy-nine subjects had data for weight at a later visit (mean follow-up = 4.3 ± 1.9 years) to calculate percent weight change per year. RESULTS: Erythropoietin, adjusted for covariates, correlated with 24-h EE (r = 0.26, P = 0.007), sleeping EE (r = 0.29, P = 0.003), fat-free mass (r = 0.19, P = 0.05), and fat mass (r = 0.27, P = 0.005), but not insulin or glucose measures. The association of erythropoietin with 24-h EE was fully mediated by fat-free mass. Erythropoietin associated with leptin in women (ρ = 0.36, P = 0.01), but not in men (P = 0.9), independently from fat mass. The association of erythropoietin with percent weight change per year was in opposing directions (interaction: P = 0.002) in males (r = -0.35, P = 0.02) versus females (r = 0.37, P = 0.02). CONCLUSIONS: Non-hematopoietic endogenous erythropoietin action may be involved in body weight regulation in opposing directions in men and women, i.e., weight loss in men and weight gain in women.

Higher Daily Energy Expenditure and Respiratory Quotient, Rather Than Fat-Free Mass, Independently Determine Greater ad Libitum Overeating.

CONTEXT: Body fat-free mass (FFM), energy expenditure (EE), and respiratory quotient (RQ) are known predictors of daily food intake. Because FFM largely determines EE, it is unclear whether body composition per se or the underlying metabolism drives dietary intake. OBJECTIVE: The objective of the study was to test whether 24-hour measures of EE and RQ and their components influence ad libitum food intake independently of FFM. DESIGN AND PARTICIPANTS: One hundred seven healthy individuals (62 males/45 females, 84 Native Americans/23 whites; age 33 ± 8 y; body mass index 33 ± 8 kg/m(2); body fat 31% ± 8%) had 24-hour measures of EE in a whole-room indirect calorimeter during energy balance, followed by 3 days of ad libitum food intake using computerized vending machine systems. Body composition was estimated by dual-energy x-ray absorptiometry. MAIN OUTCOME MEASURES: FFM, 24-hour EE, RQ, spontaneous physical activity, sleeping EE (sleeping metabolic rate), awake and fed thermogenesis, and ad libitum food intake (INTAKE) were measured. RESULTS: Higher 24-hour RQ (P < .001, partial R(2) = 16%) and EE (P = .01, partial R(2) = 7%), but not FFM (P = .65), were independent predictors of INTAKE. Mediation analysis demonstrated that 24-hour EE is responsible for 80% of the FFM effect on INTAKE (44.5 ± 16.9 kcal ingested per kilogram of FFM, P= .01), whereas the unique effect due to solely FFM was negligible (10.6 ± 23.2, P = .65). Spontaneous physical activity (r = 0.33, P = .001), but not sleeping metabolic rate (P = .71), positively predicted INTAKE, whereas higher awake and fed thermogenesis determined greater INTAKE only in subjects with a body mass index of 29 kg/m(2) or less (r = 0.44, P = .01). CONCLUSIONS: EE and RQ, rather than FFM, independently determine INTAKE, suggesting that competitive energy-sensing mechanisms driven by the preferential macronutrient oxidation and total energy demands may regulate food intake.

Fasting hyperglycemia predicts lower rates of weight gain by increased energy expenditure and fat oxidation rate.

CONTEXT: Increased adiposity and insulin resistance are associated with hyperglycemia and previous studies have reported that higher glucoses are associated with lower rates of weight gain. One possible mechanism is via increased energy expenditure (EE). OBJECTIVE: To assess the relationships between changes in EE during spontaneous weight gain and concomitant changes in glucose levels. DESIGN AND PARTICIPANTS: Body composition, metabolic, and glycemic data were available from nondiabetic Native Americans who underwent two measurements of 24-h EE during eucaloric feeding in a metabolic chamber (N = 144; time between measurements: 5.0 ± 3.3 years) or resting EE by ventilated hood system during the euglycemic-hyperinsulinemic clamp (N = 261; 4.5 ± 3.2 years). Long-term follow-up data (8.3 ± 4.3 years) for weight and body composition were available in 131 and 122 subjects, respectively. MAIN OUTCOME MEASURES: Twenty four hour EE and respiratory quotient (RQ), resting (RMR), and sleeping (SMR) metabolic rates, glucose, and insulin levels, basal glucose output (BGO). RESULTS: Weight gain-associated increase in fasting plasma glucose (FPG) levels was accompanied with decreased 24-h RQ (partial R = -0.24, P = .002) and increased 24-h EE, RMR, SMR, and fat oxidation after accounting for changes in body composition (partial R: 0.12 to 0.19, all P ≤ .05). Upon weight gain, BGO tended to increase (P = .07), while insulin infusion induced a decrease in EE (P = .04). Higher baseline FPG predicted lower rates of future weight gain (partial R = -0.18, P = .04). CONCLUSIONS: Higher FPG after weight gain was associated with greater-than-expected increase in EE. The rise in BGO and the insulin-induced EE suppression at follow-up indicate that increased hepatic gluconeogenesis may be an important mediator of EE changes associated with weight gain.

Energy Expenditure Responses to Fasting and Overfeeding Identify Phenotypes Associated With Weight Change.

Because it is unknown whether 24-h energy expenditure (EE) responses to dietary extremes will identify phenotypes associated with weight regulation, the aim of this study was to determine whether such responses to fasting or overfeeding are associated with future weight change. The 24-h EE during energy balance, fasting, and four different overfeeding diets with 200% energy requirements was measured in a metabolic chamber in 37 subjects with normal glucose regulation while they resided on our clinical research unit. Diets were given for 24 h each and included the following: (1) low protein (3%), (2) standard (50% carbohydrate, 20% protein), (3) high fat (60%), and (4) high carbohydrate (75%). Participants returned for follow-up 6 months after the initial measures. The decrease in 24-h EE during fasting and the increase with overfeeding were correlated. A larger reduction in EE during fasting, a smaller EE response to low-protein overfeeding, and a larger response to high-carbohydrate overfeeding all correlated with weight gain. The association of the fasting EE response with weight change was not independent from that of low protein in a multivariate model. We identified the following two independent propensities associated with weight gain: a predilection for conserving energy during caloric and protein deprivation and a profligate response to large amounts of carbohydrates.

The effect of differing patterns of childhood body mass index gain on adult physiology in American Indians.

OBJECTIVE: Identifying groups of individuals with similar patterns of body mass index (BMI) change during childhood may increase understanding of the relationship between childhood BMI and adult health. METHODS: Discrete classes of BMI z-score change were determined in 1,920 American Indian children with at least four non diabetic health examinations between the ages of 2 and 18 years using latent class trajectory analysis. In subsets of subjects, data were available for melanocortin-4 receptor (MC4R) sequencing; in utero exposure to type 2 diabetes (T2D); or, as adults, oral glucose tolerance tests, onset of T2D, or body composition. RESULTS: Six separate groups were identified. Individuals with a more modern birth year, an MC4R mutation, or in utero exposure to T2D were clustered in the two groups with high increasing and chronic overweight z-scores (P < 0.0001). The z-score classes predicted adult percent fat (P < 0.0001, partial r(2) = 0.18 adjusted for covariates). There was a greater risk for T2D, independent from adult BMI, in three classes (lean increasing to overweight, high increasing, and chronic overweight z-scores) compared to the two leanest groups (respectively: HRR= 3.2, P = 0.01; 6.0, P = 0.0003; 11.6, P < 0.0001). CONCLUSIONS: Distinct patterns of childhood BMI z-score change associate with adult adiposity and may impact risk of T2D.