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Objective: The existence of seasonal changes in energy metabolism is uncertain. We investigated the relationship between the seasons and spontaneous physical activity (SPA), energy expenditure (EE), and other components measured in a respiratory chamber. Methods: Between 1985–2005, 671 healthy adults (aged 28.8 ± 7.1 years; 403 men) in Phoenix, Arizona had a 24-hour stay in the respiratory chamber equipped with radar sensors; SPA (expressed as a percentage over the time interval), the energy cost of SPA, EE, and respiratory exchange ratio (RER) were measured. Results: In models adjusted for known covariates, SPA (%) was lower during summer (7.2 ± 2.9, p = 0.0002), spring (7.5 ± 2.9, p = 0.025), and fall (7.6 ± 3, p = 0.038) compared to winter (8.3 ± 3.5, reference). Conversely, energy cost of SPA (kcal/h/%) was higher during summer (2.18 ± 0.83, p = 0.0008), spring (2.186 ± 0.83, p = 0.017), and fall (2.146 ± 0.75, p = 0.038) compared to winter (2.006 ± 0.76). Protein (292 ± 117 kcal/day, β = −21.2, p = 0.08) oxidation rates was lower in the summer compared to winter. Carbohydrate and lipid oxidation rates (kcal/day) did not differ across seasons. RER and 24-h EE did not differ by season. Conclusion: SPA, representing fidgeting-like behavior in the chamber, demonstrated a winter peak and summer nadir in humans living in a desert climate. These findings indicate that the physiological propensity for movement may be affected by seasonal factors. Clinical trial registration: ClinicalTrials.gov identifiers: NCT00340132, NCT00342732 [ABSTRACT FROM AUTHOR]

Background Naturally occurring carbon and nitrogen stable isotope ratios [13C/12C (CIR) and 15N/14N (NIR)] are promising dietary biomarkers. As these candidate biomarkers have long tissue residence times, long-term feeding studies are needed for their evaluation. Objective Our aim was to evaluate plasma, RBCs, and hair CIR and NIR as biomarkers of fish, meat, and sugar-sweetened beverage (SSB) intake in a 12-wk dietary intervention. Methods Thirty-two men (aged 46.2 ± 10.5 y; BMI: 27.2 ± 4.0 kg/m2) underwent a 12-wk inpatient dietary intervention at the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) in Phoenix, Arizona. The effects of fish, meat, and SSB intake on CIR and NIR were evaluated using a balanced factorial design, with each intake factor at 2 levels (present/absent) in a common, background diet (50% carbohydrate, 30% fat, 20% protein). Fasting blood samples were taken biweekly from baseline, and hair samples were collected at baseline and postintervention. Data were analyzed using multivariable regression. Results The postintervention CIR of plasma was elevated when diets included meat (β = 0.89, 95% CI: 0.73,1.05) and SSBs (β = 0.48, 95% CI: 0.32, 0.64). The postintervention NIR of plasma was elevated when diets included fish (β = 0.85, 95% CI: 0.64, 1.05) and meat (β = 0.61, 95% CI: 0.42, 0.8). Results were similar for RBCs and hair. Postintervention RBC CIR and NIR had strong associations with baseline, suggesting that turnover to the intervention diets was incomplete after 12 wk. Estimates of isotopic turnover rate further confirmed incomplete turnover of RBCs. Conclusions CIR was associated with meat and SSBs, and more strongly with meat. NIR was associated with fish and meat, and more strongly with fish. Overall, CIR and NIR discriminated between dietary fish and meat, and to a lesser extent SSBs, indicating their potential utility as biomarkers of intake in US diets. Approaches to make these biomarkers more specific are needed. This trial was registered at clinicaltrials.gov as NCT01237093. [ABSTRACT FROM AUTHOR]

Pima Indians living in Arizona have a high prevalence of obesity, and we have previously shown that a relatively lower energy expenditure (EE) predicts weight and fat mass gain in this population. EE is a familial trait (heritability = 0.52); therefore, in the current study, we aimed to identify genetic variants that affect EE and thereby influence BMI and body fatness in Pima Indians. Genotypic data from 491,265 variants were analyzed for association with resting metabolic rate (RMR) and 24-h EE assessed in a whole-room calorimeter in 507 and 419 Pima Indians, respectively. Variants associated with both measures of EE were analyzed for association with maximum BMI and percent body fat (PFAT) in 5,870 and 912 Pima Indians, respectively. rs11014566 nominally associated with both measures of EE and both measures of adiposity in Pima Indians, where the G allele (frequency: Pima Indians = 0.60, Europeans <0.01) associated with lower 24-h EE (β = -33 kcal/day per copy), lower RMR (β = -31 kcal/day), higher BMI (β = +0.6 kg/m2), and higher PFAT (β = +0.9%). However, the association of rs11014566 with BMI did not directionally replicate when assessed in other ethnic groups. rs11014566 tags rs144895904, which affected promoter function in an in vitro luciferase assay. These variants map to GPR158, which is highly expressed in the brain and interacts with two other genes (RGS7 and CACNA1B) known to affect obesity in knockout mice. Our results suggest that common ethnic-specific variation in GPR158 may influence EE; however, its role in weight gain remains controversial, as it either had no association with BMI or associated with BMI but in the opposite direction in other ethnic groups. [ABSTRACT FROM AUTHOR]

Missense variants in KCNJ11 and ABCC8, which encode the KIR6.2 and SUR1 subunits of the β-cell KATP channel, have previously been implicated in type 2 diabetes, neonatal diabetes, and hyperinsulinemic hypoglycemia of infancy (HHI). To determine whether variation in these genes affects risk for type 2 diabetes or increased birth weight as a consequence of fetal hyperinsulinemia in Pima Indians, missense and common noncoding variants were analyzed in individuals living in the Gila River Indian Community. A R1420H variant in SUR1 (ABCC8) was identified in 3.3% of the population (N = 7,710). R1420H carriers had higher mean birth weights and a twofold increased risk for type 2 diabetes with a 7-year earlier onset age despite being leaner than noncarriers. One individual homozygous for R1420H was identified; retrospective review of his medical records was consistent with HHI and a diagnosis of diabetes at age 3.5 years. In vitro studies showed that the R1420H substitution decreases KATP channel activity. Identification of this loss-of-function variant in ABCC8 with a carrier frequency of 3.3% affects clinical care as homozygous inheritance and potential HHI will occur in 1/3,600 births in this American Indian population. [ABSTRACT FROM AUTHOR]

Background: Isocaloric manipulation of carbohydrate or fat intake could alter subsequent ad libitum food intake. Methods: In a controlled inpatient study, we investigated whether isocaloric manipulation of carbohydrate or fat would alter subsequent ad libitum energy intake. Eighteen non-diabetic subjects (age range 19-53 years.; 15 M/3F; % body fat 38.5 ± 9.1 (mean ± SD)) were fed for 3 days an isocaloric high-carbohydrate diet (HC; 60% carbohydrate, 20% fat, 20% protein) and a high-fat diet (HF; 50% fat, 30% carbohydrate, 20% protein) in random order each followed by 3 days of ad libitum food intake. Results: There were no differences in mean daily energy intake (EI) following each diet (HC vs. HF: 4,811 ± 1,190 vs. 4,823 ± 1,238 kcal/d; P = 0.7) or in the percent of weight maintenance energy needs (%EN-WM; 173 ± 41 vs. 173 ± 46%, P = 0.5). However, the individual difference in EI between the HF versus HC diet (ΔEI) both on day one and over the 3 days of each ad libitum period was negatively associated with % body fat (%BF) and waist circumference (day 1: ΔEI vs. %BF, r = −0.49, P = 0.04; mean day 1-3 kcal ΔEI vs. %BF, r = −0.66, P = 0.003, and ΔEI vs. waist, r = −0.65, P = 0.004). Conclusions: A short-term isocaloric HC diet did not result in overall lower EI compared with a HF diet in the same individuals. However, we did find that increasing body fat was associated with less decline in EI following the HC versus HF diet indicating that increasing adiposity is associated with altered regulation of EI in response to macronutrient changes. [ABSTRACT FROM AUTHOR]

OBJECTIVE--In severely obese individuals and patients with diabetes, accumulation and activation of macrophages in adipose tissue has been implicated in the development of obesity-associated complications, including insulin resistance. We sought to determine whether in a healthy population, adiposity, sex, age, or insulin action is associated with adipose tissue macrophage content (ATMc) and/or markers of macrophage activation. RESEARCH DESIGN AND METHODS--Subcutaneous ATMc from young adult Pima Indians with a wide range of adiposity (13-46% body fat, by whole-body dual-energy X-ray absorptiometry) and insulin action (glucose disposal rate 1.6-9 mg/kg estimated metabolic body size/min, by glucose clamp) were measured. We also measured expression in adipose, tissue of factors implicated in macrophage recruitment and activation to determine any association with ATMc and insulin action. RESULTS--ATMc, as assessed by immunohistochemistry (Mphi) and by macrophage-specific gene expression (CD68, CD11b, and CSF1R), were correlated with percent body fat, age, and female sex. Gene expression of CD68, CD11b, and CSF1R but not Mphi was correlated negatively with glucose disposal rate but not after adjustment for percent body fat, age, and sex. However, adipose tissue expression of plasminogen activator inhibitor type-1 (PAI-1) and CD11 antigen-like family member C (CD11c), markers produced by macrophages, were negatively correlated with adjusted glucose disposal rate (r = -0.28, P = 0.05 and r = -0.31, P = 0.03). CONCLUSIONS--ATMc is correlated with age and adiposity but not with insulin action independent of adiposity in healthy human subjects. However, PAI-1 and CD11c expression are independent predictors of insulin action, indicating a possible role for adipose tissue macrophage activation. Diabetes 58: 385-393, 2009 [ABSTRACT FROM AUTHOR]

Background Accurate prediction of 24-hour energy expenditure (24EE) relies on knowing body composition, in particular fat-free mass (FFM), the largest determinant of 24EE. FFM is closely correlated with hematologic volumes: blood volume (BV), red cell mass (RCM), and plasma volume (PV). However, it is unknown whether predicted hematologic volumes, based on easily collected variables, can improve 24EE prediction. Objective The aim was to develop and validate equations to predict 24EE based on predicted BV, RCM, and PV and to compare the accuracy and agreement with models developed from FFM and with the Mifflin-St Jeor equation, which is recommended for clinical use by the Academy of Nutrition and Dietetics. Design Participants had body composition measured by underwater weighing and 24EE by respiratory chamber. BV, RCM, and PV were calculated from five published equations. Participants/setting Native American and white men and women were studied (n=351). Participants were healthy adults aged 18 to 49 years from the Phoenix, AZ, metropolitan area. Main outcome measure Accuracy to within ±10% of measured 24EE and agreement by Bland-Altman analysis. Statistical analysis Regression models to predict 24EE from hematologic and body composition variables were developed in half the dataset and validated in the other half. Results Hematologic volumes were all strongly correlated with FFM in both men and women ( r ≥0.94). Whereas the accuracy of FFM alone was 69%, four hematologic volumes were individually more accurate (75% to 78%) in predicting 24EE. Equations based on hematologic volumes plus demographics had mean prediction errors comparable to those based on body composition plus demographics; although the Mifflin-St Jeor had modestly better mean prediction error, body composition, hematologic, and Mifflin-St Jeor models all had similar accuracy (approximately 80%). Conclusions Prediction equations based on hematologic volumes were developed, validated, and found to be comparable to Mifflin-St Jeor and body composition models in this population of healthy adults. [ABSTRACT FROM AUTHOR]