Search

Abstract: Introduction: Obesity is a major risk factor for the development of endometrial cancer (EC). An improved understanding of biologic mechanisms associated with weight loss, including alteration in inflammation, hormonal balance, and cancer antigens expression may lead to the development of effective cancer prevention strategies. The goal of this study was to explore longitudinal biomarker changes in obese women who underwent weight loss intervention, testing the hypothesis biomarker levels can be altered through intentional weight loss. Methods: Serum samples from 89 participants with Class II and Class III obesity and 43 non morbidly obese comparisons were obtained in Re-Energize with Nutrition, Exercise and Weight Loss (RENEW) study as previously reported. Twenty-one bead-based xMAP immunoassays were utilized, including cancer-associated antigens, cytokines, chemokines, and hormones. One-way repeated measures ANOVA was used to examine the association between changes in biomarker expression levels over time (baseline, 6months and 12months). Linear mixed effects models were used to examine longitudinal relationships between biomarker expression levels. Results: Mean levels of VEGF, soluble E-selectin, GH, adiponectin, IL-6, IL-7, CA-125, and IGFBP-1 significantly differed between time periods. In adjusted mixed linear models, decreasing BMI was significantly associated with lower levels of soluble E-selectin and IL-6 and increases in GH, adiponectin, and IGFBP-1. Conclusions: This is one of the first efforts to explore changes in cancer-associated biomarkers in a cohort of weight loss research participants at high risk for EC development. Our findings demonstrate that changes in the expression of markers can be achieved with weight loss intervention. [Copyright &y& Elsevier]

Background: Functional dependence and the risks of disability increase with age. The loss of independence is thought to be partially due to a decrease in physical activity. However, in populations, accurate measurement of physical activity is challenging and may not provide information on functional impairment.Methods: This study therefore assessed physical functionality and physical activity level in a group of nonagenarians (11 men/11 women; 93+/-1 years, 66.6+/-2.4 kg, body mass index [BMI]=24+/-1 kg/m2) and a group of participants aged 60-74 years (17 men/15 women; 70+/-1 years, 83.3+/-3.0 kg, BMI=29+/-1 kg/m2) from the Louisiana Healthy Aging Study. Physical activity level was calculated from total energy expenditure (TEE) and resting metabolic rate (RMR). Physical functionality was assessed using the Reduced Continuous Scale Physical Functional Performance Test (CS-PFP10).Results: Nonagenarians had lower absolute (p<.001) and adjusted (p<.007) TEE compared to participants aged 60-74 years which was attributed to a reduction in both RMR and physical activity level. Nonagenarians also had reduced functional performance (p<.001) which was correlated with activity level (r=0.68, p<.001).Conclusions: When compared to individuals aged 60-74 years, 73% of the reduction in TEE in nonagenarians can be attributed to a reduction in physical activity level, the remaining being accounted for by a reduction in RMR. The reduced physical activity in nonagenarians is associated with less physical functionality. This study provides the first objective comparison of physical functionality and actual levels of physical activity in older individuals. [ABSTRACT FROM AUTHOR]

Context: Prolonged calorie restriction increases life span in rodents. Whether prolonged calorie restriction affects biomarkers of longevity or markers of oxidative stress, or reduces metabolic rate beyond that expected from reduced metabolic mass, has not been investigated in humans.Objective: To examine the effects of 6 months of calorie restriction, with or without exercise, in overweight, nonobese (body mass index, 25 to <30) men and women.Design, Setting, and Participants: Randomized controlled trial of healthy, sedentary men and women (N = 48) conducted between March 2002 and August 2004 at a research center in Baton Rouge, La.Intervention: Participants were randomized to 1 of 4 groups for 6 months: control (weight maintenance diet); calorie restriction (25% calorie restriction of baseline energy requirements); calorie restriction with exercise (12.5% calorie restriction plus 12.5% increase in energy expenditure by structured exercise); very low-calorie diet (890 kcal/d until 15% weight reduction, followed by a weight maintenance diet).Main Outcome Measures: Body composition; dehydroepiandrosterone sulfate (DHEAS), glucose, and insulin levels; protein carbonyls; DNA damage; 24-hour energy expenditure; and core body temperature.Results: Mean (SEM) weight change at 6 months in the 4 groups was as follows: controls, -1.0% (1.1%); calorie restriction, -10.4% (0.9%); calorie restriction with exercise, -10.0% (0.8%); and very low-calorie diet, -13.9% (0.7%). At 6 months, fasting insulin levels were significantly reduced from baseline in the intervention groups (all P<.01), whereas DHEAS and glucose levels were unchanged. Core body temperature was reduced in the calorie restriction and calorie restriction with exercise groups (both P<.05). After adjustment for changes in body composition, sedentary 24-hour energy expenditure was unchanged in controls, but decreased in the calorie restriction (-135 kcal/d [42 kcal/d]), calorie restriction with exercise (-117 kcal/d [52 kcal/d]), and very low-calorie diet (-125 kcal/d [35 kcal/d]) groups (all P<.008). These "metabolic adaptations" (~ 6% more than expected based on loss of metabolic mass) were statistically different from controls (P<.05). Protein carbonyl concentrations were not changed from baseline to month 6 in any group, whereas DNA damage was also reduced from baseline in all intervention groups (P <.005).Conclusions: Our findings suggest that 2 biomarkers of longevity (fasting insulin level and body temperature) are decreased by prolonged calorie restriction in humans and support the theory that metabolic rate is reduced beyond the level expected from reduced metabolic body mass. Studies of longer duration are required to determine if calorie restriction attenuates the aging process in humans.Trial Registration: ClinicalTrials.gov Identifier: NCT00099151. [ABSTRACT FROM AUTHOR]

Abstract: Energy requirements of military personnel (Soldiers, Sailors, Airmen, and Marines) have been measured in garrison and in field training under a variety of climatic conditions. Group mean total energy expenditures for 424 male military personnel from various units engaged in diverse missions ranged from 13.0 to 29.8MJ (3109–7131kcal) per day. The overall mean was 19.3±2.7MJ (mean±SD) (4610±650kcal) per day measured over an average of 12.2 days (range 2.25–69 days). For the 77 female military personnel studied, mean total energy expenditures for individual experimental groups ranged from 9.8 to 23.4MJ (2332–5597kcal) per day, with an overall mean of 11.9±2.6MJ (2850±620kcal) per day, measured over an average of 8.8 days (range 2.25–14 days). Women, presumably due to their lower lean body mass, resting metabolic rate, and absolute work rates, had lower total energy expenditures. Combat training produced higher energy requirements than non-combat training or support activities. Compared to temperate conditions, total energy expenditures did not appear to be influenced by hot weather, but tended to be higher in the cold or high altitude conditions. [Copyright &y& Elsevier]

Background Underreporting of food intake has been commonly observed. We hypothesized that experience with recording dietary information might increase the accuracy of the records. To test this hypothesis, we compared energy intake and energy expenditure in dietitians—who are experienced in recording food intake—with those of non-dietitians, whose only exposure to training to record food was in the context of this trial.Subjects/setting Subjects for this study were 10 female registered dietitians and 10 women of comparable age and weight who were not dietitians.Design This study compared the energy intake obtained from 7-day food records with energy expenditure measured over the corresponding 7-day period using doubly labeled water.Statistical analysis Data were compared by an analysis of variance.Methods All subjects were trained to provide a 7-day weighed food intake record. Energy expenditure was measured with doubly labeled water over the 7 days when the weighed food intake record was obtained. A total of 10 dietitians and a control of group of 10 women of similar age and weight were recruited for this study. Participants were told that the goal was to record food intake as accurately as possible, because it would be compared with the simultaneous measurement of energy expenditure determined by doubly labeled water.Results: The energy expenditure of the dietitians and controls were not different (2,154±105 [mean±standard error of the mean] kcal/day for dietitians and 2,315±90 kcal/ day for controls). The dietitians underreported their energy intake obtained from the food records by an average of 223±116 kcal/day, which was not different from their energy expenditure. Participants in the control group, as hypothesized, significantly underreported their energy intake (429±142 kcal/day, P<.05).Conclusion Dietitians estimated their energy intake more accurately than non-dietitians, suggesting that familiarity with and interest in keeping food records may lead to more reliable estimates of energy intake. J Am Diet Assoc. 2002; 102:1428-1432. [Copyright &y& Elsevier]

Dietary fat and its relation to obesity has been a controversial issue for several years. In this review, several kinds of data relating to this issue are presented. There are epidemiological cross-country data and data within countries showing an effect. However, in the United States, the intake of fat appears to be declining, whereas the prevalence of obesity rises-the American Paradox. Clinical studies show that trans fatty acids can increase insulin resistance and that exercise can enhance the rate of adaptation to a high fat diet by increasing the rate of fat oxidation. The differences in response of inflammatory signals and of insulin resistance to different fatty acids indicate that not all fatty acids are the same. There are also experimental data showing that most, but not all, animals consuming a high fat diet will become obese. A number of mechanisms have been postulated for this difference, including differential sensitivities to neurotransmitters, to the intestinal peptide, enterostatin, and to individual fatty acids. One important conclusion from this review is that both total fat and individual fatty acids have to be considered when reaching conclusions about dietary fat and obesity. [ABSTRACT FROM AUTHOR]

Study Design: Cross-sectional validation study., Objectives: To develop a raw acceleration signal-based random forest (RF) model for predicting total energy expenditure (TEE) in manual wheelchair users (MWUs) and evaluate the preliminary field validity of this new model, along with four existing models published in prior literature, using the Doubly Labeled Water (DLW) method., Setting: General community and research institution in Pittsburgh, USA., Methods: A total of 78 participants' data from two previous studies were used to develop the new RF model. A seven-day cross-sectional study was conducted to collect participants' free-living physical activity and TEE data, resting metabolic rate, demographics, and anthropometrics. Ten MWUs with spinal cord injury (SCI) completed the study, with seven participants having valid data for evaluating the preliminary field validity of the five models., Results: The RF model achieved a mean absolute error (MAE) of 0.59 ± 0.60 kcal/min and a mean absolute percentage error (MAPE) of 23.6% ± 24.3% on the validation set. For preliminary field validation, the five assessed models yielded MAE from 136 kcal/day to 1141 kcal/day and MAPE from 6.1% to 50.2%. The model developed by Nightingale et al. in 2015 achieved the best performance (MAE: 136 ± 96 kcal/day, MAPE: 6.1% ± 4.7%), while the RF model achieved comparable performance (MAE: 167 ± 99 kcal/day, MAPE: 7.4% ± 5.1%)., Conclusions: Two existing models and our newly developed RF model showed good preliminary field validity for assessing TEE in MWUs with SCI and the potential to detect lifestyle change in this population. Future large-scale field validation studies and model iteration are recommended., (© 2024. The Author(s), under exclusive licence to International Spinal Cord Society.)

Objectives: Non-Hispanic black women (BW) have a greater risk of type 2 diabetes (T2D) and insulin resistance (IR) compared to non-Hispanic white women (WW). The mechanisms leading to these differences are not understood, and it is unclear whether synergistic effects of race and obesity impact disease risk. To understand the interaction of race and weight, hepatic and peripheral IR were compared in WW and BW with and without obesity., Methods: Hepatic and peripheral IR was measured by a labeled, hyperinsulinemic-euglycemic clamp in BW (n=32) and WW (n=32) with and without obesity. Measurements of body composition, cardiorespiratory fitness, and skeletal muscle (SM) respiration were completed. Data were analyzed by mixed model ANOVA., Results: Subjects with obesity had greater hepatic and peripheral IR and lower SM respiration (P<0.001). Despite 14% greater insulin (P=0.066), BW tended to have lower peripheral glucose disposal (Rd; P=0.062), which was driven by women without obesity (P=0.002). BW had significantly lower glucose production (P=0.005), hepatic IR (P=0.024), and maximal coupled and uncoupled respiration (P<0.001) than WW. Maximal coupled and uncoupled SM mitochondrial respiration was strongly correlated with peripheral and hepatic IR (P<0.01)., Conclusion: While BW without obesity had lower Rd than WW, race and obesity did not synergistically impact peripheral IR. Paradoxically, WW with obesity had greater hepatic IR compared to BW. Relationships between SM respiration and IR persisted across a range of body weight. These data provide support for therapies in BW, like exercise, that improve SM mitochondrial respiration to reduce IR and T2D risk., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.)

Understanding the factors that contribute to exercise response variation is the first step in achieving the goal of developing personalized exercise prescriptions. This review discusses the key molecular and other mechanistic factors, both extrinsic and intrinsic, that influence exercise responses and health outcomes. Extrinsic characteristics include the timing and dose of exercise, circadian rhythms, sleep habits, dietary interactions, and medication use, whereas intrinsic factors such as sex, age, hormonal status, race/ethnicity, and genetics are also integral. The molecular transducers of exercise (i.e., genomic/epigenomic, proteomic/post-translational, transcriptomic, metabolic/metabolomic, and lipidomic elements) are considered with respect to variability in physiological and health outcomes. Finally, this review highlights the current challenges that impede our ability to develop effective personalized exercise prescriptions. The Molecular Transducers of Physical Activity Consortium (MoTrPAC) aims to fill significant gaps in the understanding of exercise response variability, yet further investigations are needed to address additional health outcomes across all populations., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: The prevalence of type 2 diabetes in African American women (AAW) is nearly twice that of White women. Lower insulin sensitivity and decreased mitochondrial function may be contributing factors. The purpose of this study was to compare fat oxidation in AAW and White women., Methods: Participants were 22 AAW and 22 White women, matched for age (18.7-38.3 years) and BMI (< 28 kg/m 2 ). Participants completed two submaximal (50% VO 2 max) exercise tests with indirect calorimetry and stable isotope tracers to assess total, plasma, and intramyocellular triglyceride fat oxidation., Results: The respiratory quotient during the exercise test was nearly identical in AAW and White women (0.813 ± 0.008 vs. 0.810 ± 0.008, p = 0.83). Although absolute total and plasma fat oxidation was lower in AAW, adjusting for the lower workload in AAW eliminated these racial differences. There was no racial difference in plasma and intramyocellular triglyceride source of fat for oxidation. No racial differences were observed in rates of ex vivo fat oxidation. Exercise efficiency was lower in AAW when adjusted to leg fat free mass., Conclusions: The data suggest that fat oxidation is not lower in AAW compared with White women, but additional studies are needed across exercise intensity, body weight, and age to confirm these results., (© 2023 The Obesity Society.)

Metabolic routing of nicotinamide (NAM) to NAD + or 1-methylnicotinamide (MeNAM) has impacts on human health and aging. NAM is imported by cells or liberated from NAD + . The fate of 2 H 4 -NAM in cultured cells, mice, and humans was determined by stable isotope tracing. 2 H 4 -NAM is an NAD + precursor via the salvage pathway in cultured A549 cells and human PBMCs and in A549 cell xenografts and PBMCs from 2 H 4 -NAM-dosed mice and humans, respectively. 2 H 4 -NAM is a MeNAM precursor in A549 cell cultures and xenografts, but not isolated PBMCs. NAM released from NAD + is a poor MeNAM precursor. Additional A549 cell tracer studies yielded further mechanistic insight. NAMPT activators promote NAD + synthesis and consumption. Surprisingly, NAM liberated from NAD + in NAMPT activator-treated A549 cells is also routed toward MeNAM production. Metabolic fate mapping of the dual NAM sources across the translational spectrum (cells, mice, humans) illuminates a key regulatory node governing NAD + and MeNAM synthesis., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

The basis of medical nutrition therapy for patients with LC-FAODs is to provide adequate energy to maintain anabolism and prevent catabolism. In practice, energy needs are estimated based on formulas derived from normal populations but it is unknown if energy expenditure among patients with LC-FAODs is similar to the normal population. We measured resting energy expenditure (REE), total energy expenditure (TEE) and body composition in 31 subjects with LC-FAODs ranging in age from 7 to 64 years. Measured REE was lower than estimated REE by various prediction equations and measured TEE was lower than estimated TEE. It is possible that the lower energy expenditure based on prediction formulas from the normal population is due to differences in body composition; we compared body composition to normal data from the 2017-18 National Health and Nutrition Examination Survey (NHANES). Fat free mass and fat mass was similar between subjects with an LC-FAOD and NHANES normal data suggesting no difference in body composition. We then compared measured REE and TEE to normal published data from the Dietary Reference Intakes (DRI). Measured REE and TEE were significantly lower among subjects with LC-FAODs compared to normal published energy expenditure data. Our results suggests patients with a LC-FAOD exhibit a lower REE and therefore actually have a slightly lower TEE than estimated. Current prediction equations may overestimate energy expenditure of patients with a LC-FAOD., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: The aim of this study was to understand whether the paradoxical association of missense variant rs373863828 in CREB3 regulatory factor (CREBRF) with higher BMI but lower odds of diabetes is explained by either metabolically favorable body fat distribution or greater fat-free mass., Methods: This study explored the association of the minor allele with dual-energy x-ray absorptiometry-derived body composition in n = 421 Samoans and used path analysis to examine the mediating role of fat and fat-free mass on the relationship between rs373863828 and fasting glucose., Results: Among females, the rs373863828 minor A allele was associated with greater BMI. There was no association of genotype with percent body fat, visceral adiposity, or fat distribution in either sex. In both females and males, lean mass was greater with each A allele: 2.16 kg/copy (p = 0.0001) and 1.73 kg/copy (p = 0.02), respectively. Path analysis showed a direct negative effect of rs373863828 genotype on fasting glucose (p = 0.004) consistent with previous findings, but also an indirect positive effect on fasting glucose operating through fat-free mass (p = 0.027)., Conclusions: The protective effect of rs373863828 in CREBRF, common among Pacific Islanders, on type 2 diabetes does not operate through body composition. Rather, the variant's effects on body size/composition and fasting glucose likely operate via different, tissue-specific mechanisms., (© 2022 The Obesity Society.)

Background and Aims: The primary goals of this study were to clarify 1) the effect of weight loss by lifestyle intervention on circulating total angiopoietin-like protein 8 (ANGPTL8), and 2) the role of physical activity on serum total ANGPTL8 in northern Americans with obesity but without diabetes., Methods and Results: A total of 130 subjects with body mass index (BMI) ≧ 35 kg/m 2 but without diabetes were recruited, and 121 subjects completed a weight loss program for data analysis. Abdominal adipose tissue was determined by non-contrast computed tomography (CT). Serum total ANGPTL8 was higher in the group with obesity than in the lean control group. Serum total ANGPTL8 was positively correlated with waist circumference (WC), BMI, fasting insulin, HOMA-IR, HOMA-B, QUICKI, hs-CRP, IL-6, and leptin. Serum total ANGPTL8 did not significantly differ between the two intervention groups at baseline, and it was significantly lower after weight loss, with comparable changes with diet only and diet plus physical activity., Conclusion: Among northern Americans with obesity but without diabetes, a lifestyle modification resulted in significant reduction of circulating total ANGPTL8 concentrations in a 6-month weight-loss period. Although addition of physical activity resulted in greater total and liver fat loss, it did not promote further significant decline of serum total ANGPTL8 beyond diet alone., Competing Interests: Declaration of competing interest All authors disclose no conflict of interest., (Copyright © 2022 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background: Samoa is a Pacific Island country facing one of the highest burdens of non-communicable disease globally., Methods: In this study, we apply a cascade-of-care approach to understand gaps in the awareness, treatment, and control cascade of diabetes and hypertension in a cross-sectional, convenience sample of 703 young, high-risk Samoan adults (29.5-50.9 years)., Findings: Non-communicable diseases were prevalent in the study sample: 19.5% (95% CI: 16.6%-22.7%) of participants had diabetes; 47.6% (95% CI: 43.7%-51.4%) presented with pre-diabetes or diabetes; 31.0% (95% CI: 27.5%-34.6%) had hypertension; and nearly 90% (95% CI: 86.7%-91.5%) had overweight or obesity. Among those with diabetes and hypertension, only 20.5% (95% CI: 13.9%-28.4%) and 11.8% (95% CI: 7.8%-16.9%) of participants were aware of their condition, respectively. Only 0.8% (95% CI: 0.0%-4.2%) of all participants with diabetes had achieved glycemic control; only 2.8% (95% CI: 1.1%-6.1%) of those with hypertension achieved control., Interpretation: We found a significant burden of diabetes and hypertension in Samoa, exceeding the recent prevalence estimates of other low- to middle-income countries by nearly two-fold. A severe unmet need in both detection and subsequent control and monitoring of these chronic conditions exists. Our results suggest that the initial diagnosis and surveillance stage in the cascade of care for chronic conditions should be a major focus of primary care efforts; national screening campaigns and programs that leverage village and district nurses to deliver community-based primary care may significantly impact gap closure in the NCD cascade., Funding: This study was supported by the U.S. National Institutes of Health R01HL140570 (PIs: McGarvey and DeLany); AR was supported by NIH FIC D43TW010540; HK and AR-C were supported by the Minority Health and Health Disparities International Research Training (MHIRT) Program at Brown University, NIH Grant # 5T37MD008655., Competing Interests: The authors have no conflicts of interest to disclose., (© 2021 The Authors.)

The nitrate-nitrite-NO pathway regulates NO synthase-independent vasodilation and NO signaling. Ingestion of inorganic nitrite has vasodilatory and blood pressure-lowering effects. Preclinical studies in rodent models suggest there may be a benefit of nitrite in lowering serum triglyceride levels and improving the metabolic syndrome. In a phase 2 study, we evaluated the safety and efficacy of chronic oral nitrite therapy in patients with hypertension and the metabolic syndrome. Twenty adult subjects with stage 1 or 2 hypertension and the metabolic syndrome were enrolled in an open-label safety and efficacy study. The primary efficacy end point was blood pressure reduction; secondary end points included insulin-dependent glucose disposal and endothelial function measured by flow-mediated dilation of the brachial artery and intima-media diameter of the carotid artery. Chronic oral nitrite therapy (40 mg/3× daily) was well tolerated. Oral nitrite significantly lowered systolic, diastolic, and mean arterial pressures, but tolerance was observed after 10 to 12 weeks of therapy. There was significant improvement in the intima-media thickness of the carotid artery and trends toward improvements in flow-mediated dilation of the brachial artery and insulin sensitivity. Chronic oral nitrite therapy is safe in patients with hypertension and the metabolic syndrome. Despite an apparent lack of enzymatic tolerance to nitrite, we observed tolerance after 10 weeks of chronic therapy, which requires additional mechanistic studies and possible therapeutic dose titration in clinical trials. Nitrite may be a safe therapy to concominantly improve multiple features of the metabolic syndrome including hypertension, insulin resistance, and endothelial dysfunction. Registration- URL: https://www.clinicaltrials.gov; Unique identifier: NCT01681810.

Background: Alaska Native (AN) people have the world's highest recorded incidence of sporadic colorectal cancer (CRC) (∼91:100,000), whereas rural African (RA) people have the lowest risk (<5:100,000). Previous data supported the hypothesis that diet affected CRC risk through its effects on the colonic microbiota that produce tumor-suppressive or -promoting metabolites., Objectives: We investigated whether differences in these metabolites may contribute to the high risk of CRC in AN people., Methods: A cross-sectional observational study assessed dietary intake from 32 AN and 21 RA healthy middle-aged volunteers before screening colonoscopy. Analysis of fecal microbiota composition by 16S ribosomal RNA gene sequencing and fecal/urinary metabolites by 1H-NMR spectroscopy was complemented with targeted quantification of fecal SCFAs, bile acids, and functional microbial genes., Results: Adenomatous polyps were detected in 16 of 32 AN participants, but not found in RA participants. The AN diet contained higher proportions of fat and animal protein and less fiber. AN fecal microbiota showed a compositional predominance of Blautia and Lachnoclostridium, higher microbial capacity for bile acid conversion, and low abundance of some species involved in saccharolytic fermentation (e.g., Prevotellaceae, Ruminococcaceae), but no significant lack of butyrogenic bacteria. Significantly lower concentrations of tumor-suppressive butyrate (22.5 ± 3.1 compared with 47.2 ± 7.3 SEM µmol/g) coincided with significantly higher concentrations of tumor-promoting deoxycholic acid (26.7 ± 4.2 compared with 11 ± 1.9 µmol/g) in AN fecal samples. AN participants had lower quantities of fecal/urinary metabolites than RA participants and metabolite profiles correlated with the abundance of distinct microbial genera in feces. The main microbial and metabolic CRC-associated markers were not significantly altered in AN participants with adenomatous polyps., Conclusions: The low-fiber, high-fat diet of AN people and exposure to carcinogens derived from diet or environment are associated with a tumor-promoting colonic milieu as reflected by the high rates of adenomatous polyps in AN participants., (Copyright © The Author(s) 2019.)

Introduction: Bariatric surgery-induced weight loss may reduce resting energy expenditure (REE) and fat-free mass (FFM) disproportionately thereby predisposing patients to weight regain and sarcopenia., Methods: We compared REE and body composition of African-American and Caucasian Roux-en-Y gastric bypass (RYGB) patients after surgery with a group of non-operated controls (CON). REE by indirect calorimetry; skeletal muscle (SM), trunk organs, and brain volumes by MRI; and FFM by DXA were measured at post-surgery visits and compared with CON (N = 84) using linear regression models that adjusted for relevant covariates. Ns in RYGB were 50, 42, and 30 for anthropometry and 39, 27, 17 for MRI body composition at years 1, 2, and 5 after surgery, respectively., Results: Regression models adjusted for age, weight, height, ethnicity, and sex showed REE differences (RYGB minus CON; mean ± s.e.): year 1 (43.2 ± 34 kcal/day, p = 0.20); year 2 (- 27.9 ± 37.3 kcal/day, p = 0.46); year 5 (114.6 ± 42.3 kcal/day, p = 0.008). Analysis of FFM components showed that RYGB had greater trunk organ mass (~ 0.4 kg) and less SM (~ 1.34 kg) than CON at each visit. REE models adjusted for FFM, SM, trunk organs, and brain mass showed no between-group differences in REE (- 15.9 ± 54.8 kcal/day, p = 0.8; - 46.9 ± 64.9 kcal/day, p = 0.47; 47.7 ± 83.0 kcal/day, p = 0.57, at years 1, 2, and 5, respectively)., Conclusions: Post bariatric surgery patients maintain a larger mass of high-metabolic rate trunk organs than non-operated controls of similar anthropometrics. Interpreting REE changes after weight loss requires an accurate understanding of fat-free mass composition at both the organ and tissue levels., Clinical Trial Registration: Long-term Effects of Bariatric Surgery (LABS-2) NCT00465829.

Background: Observational reports suggest that supplementation that increases citric acid cycle intermediates via anaplerosis may have therapeutic advantages over traditional medium-chain triglyceride (MCT) treatment of long-chain fatty acid oxidation disorders (LC-FAODs) but controlled trials have not been reported. The goal of our study was to compare the effects of triheptanoin (C7), an anaplerotic seven-carbon fatty acid triglyceride, to trioctanoin (C8), an eight-carbon fatty acid triglyceride, in patients with LC-FAODs., Methods: A double blinded, randomized controlled trial of 32 subjects with LC-FAODs (carnitine palmitoyltransferase-2, very long-chain acylCoA dehydrogenase, trifunctional protein or long-chain 3-hydroxy acylCoA dehydrogenase deficiencies) who were randomly assigned a diet containing 20% of their total daily energy from either C7 or C8 for 4 months was conducted. Primary outcomes included changes in total energy expenditure (TEE), cardiac function by echocardiogram, exercise tolerance, and phosphocreatine recovery following acute exercise. Secondary outcomes included body composition, blood biomarkers, and adverse events, including incidence of rhabdomyolysis., Results: Patients in the C7 group increased left ventricular (LV) ejection fraction by 7.4% (p = 0.046) while experiencing a 20% (p = 0.041) decrease in LV wall mass on their resting echocardiogram. They also required a lower heart rate for the same amount of work during a moderate-intensity exercise stress test when compared to patients taking C8. There was no difference in TEE, phosphocreatine recovery, body composition, incidence of rhabdomyolysis, or any secondary outcome measures between the groups., Conclusions: C7 improved LV ejection fraction and reduced LV mass at rest, as well as lowering heart rate during exercise among patients with LC-FAODs., Clinical Trial Registration: Clinicaltrials.gov NCT01379625.

Importance: Questions remain about the role and durability of bariatric surgery for type 2 diabetes mellitus (T2DM)., Objective: To compare the remission of T2DM following surgical and nonsurgical treatments., Design, Setting, and Participants: In this 3-arm randomized clinical trial conducted at the University of Pittsburgh Medical Center from October 1, 2009, to June 26, 2014, in Pittsburgh, Pennsylvania, outcomes were assessed 3 years after treating 61 obese participants aged 25 to 55 years with T2DM. Analysis was conducted with an intent-to-treat population., Interventions: Participants were randomized to either an intensive lifestyle weight loss intervention for 1 year followed by a low-level lifestyle intervention for 2 years or surgical treatments (Roux-en-Y gastric bypass [RYGB] or laparoscopic adjustable gastric banding [LAGB]) followed by low-level lifestyle intervention in years 2 and 3., Main Outcomes and Measures: Primary end points were partial and complete T2DM remission and secondary end points included diabetes medications and weight change., Results: Body mass index (calculated as weight in kilograms divided by height in meters squared) was less than 35 for 26 participants (43%), 50 (82%) were women, and 13 (21%) were African American. Mean (SD) values were 100.5 (13.7) kg for weight, 47.3 (6.6) years for age, 7.8% (1.9%) for hemoglobin A1c level, and 171.3 (72.5) mg/dL for fasting plasma glucose level. Partial or complete T2DM remission was achieved by 40% (n = 8) of RYGB, 29% (n = 6) of LAGB, and no intensive lifestyle weight loss intervention participants (P = .004). The use of diabetes medications was reduced more in the surgical groups than the lifestyle intervention-alone group, with 65% of RYGB, 33% of LAGB, and none of the intensive lifestyle weight loss intervention participants going from using insulin or oral medication at baseline to no medication at year 3 (P < .001). Mean (SE) reductions in percentage of body weight at 3 years were the greatest after RYGB at 25.0% (2.0%), followed by LAGB at 15.0% (2.0%) and lifestyle treatment at 5.7% (2.4%) (P < .01)., Conclusions and Relevance: Among obese participants with T2DM, bariatric surgery with 2 years of an adjunctive low-level lifestyle intervention resulted in more disease remission than did lifestyle intervention alone., Trial Registration: clinicaltrials.gov Identifier: NCT01047735.

There is limited information on body composition, energy balance, and fitness among survivors of childhood acute lymphoblastic leukemia (ALL), especially those treated without cranial radiation therapy (CRT). This analysis compares these metrics among 365 ALL survivors with a mean age of 28.6 ± 5.9 years (149 treated with and 216 without CRT) and 365 age-, sex-, and race-matched peers. We also report risk factors for outcomes among survivors treated without CRT. Male survivors not exposed to CRT had abnormal body composition when compared with peers (% body fat, 26.2 ± 8.2 vs 22.7 ± 7.1). Survivors without CRT had similar energy balance but had significantly impaired quadriceps strength (-21.9 ± 6.0 Newton-meters [Nm]/kg, 60°/s) and endurance (-11.4 ± 4.6 Nm/kg, 300°/s), exercise capacity (-2.0 ± 2.1 ml/kg per minute), low-back and hamstring flexibility (-4.7 ± 1.6 cm), and dorsiflexion range of motion (-3.1 ± 0.9°) and higher modified total neuropathy scores (+1.6 ± 1.1) than peers. Cumulative asparaginase dose ≥120,000 IU/m(2) was associated with impaired flexibility, vincristine dose ≥39 mg/m(2) with peripheral neuropathy, glucocorticoid (prednisone equivalent) dose ≥8000 mg/m(2) with hand weakness, and intrathecal methotrexate dose ≥225 mg with dorsiflexion weakness. Physical inactivity was associated with hand weakness and decreased exercise capacity. Smoking was associated with peripheral neuropathy. Elimination of CRT from ALL therapy has improved, but not eliminated, body-composition outcomes. Survivors remain at risk for impaired fitness., (© 2015 by The American Society of Hematology.)

Visceral fat necrosis has been associated with severe acute pancreatitis (SAP) for over 100 years; however, its pathogenesis and role in SAP outcomes are poorly understood. Based on recent work suggesting that pancreatic fat lipolysis plays an important role in SAP, we evaluated the role of pancreatic lipases in SAP-associated visceral fat necrosis, the inflammatory response, local injury, and outcomes of acute pancreatitis (AP). For this, cerulein pancreatitis was induced in lean and obese mice, alone or with the lipase inhibitor orlistat and parameters of AP induction (serum amylase and lipase), fat necrosis, pancreatic necrosis, and multisystem organ failure, and inflammatory response were assessed. Pancreatic lipases were measured in fat necrosis and were overexpressed in 3T3-L1 cells. We noted obesity to convert mild cerulein AP to SAP with greater cytokines, unsaturated fatty acids (UFAs), and multisystem organ failure, and 100% mortality without affecting AP induction or pancreatic necrosis. Increased pancreatic lipase amounts and activity were noted in the extensive visceral fat necrosis of dying obese mice. Lipase inhibition reduced fat necrosis, UFAs, organ failure, and mortality but not the parameters of AP induction. Pancreatic lipase expression increased lipolysis in 3T3-L1 cells. We conclude that UFAs generated via lipolysis of visceral fat by pancreatic lipases convert mild AP to SAP independent of pancreatic necrosis and the inflammatory response., (Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Context: African-American women (AAW) have an increased risk of developing type 2 diabetes compared with Caucasian women (CW). Lower insulin sensitivity has been reported in AAW, but the reasons for this racial difference and the contributions of liver versus skeletal muscle are incompletely understood., Objective: We tested the hypothesis that young, nonobese AAW manifest lower insulin sensitivity specific to skeletal muscle, not liver, and is accompanied by lower skeletal muscle mitochondrial oxidative capacity., Participants and Main Outcome Measures: Twenty-two nonobese (body mass index 22.7 ± 3.1 kg/m(2)) AAW and 22 matched CW (body mass index 22.7 ± 3.1 kg/m(2)) underwent characterization of body composition, objectively assessed habitual physical activity, and insulin sensitivity with euglycemic clamps and stable-isotope tracers. Skeletal muscle biopsies were performed for lipid content, fiber typing, and mitochondrial measurements., Results: Peripheral insulin sensitivity was 26% lower in AAW (P < .01), but hepatic insulin sensitivity was similar between groups. Physical activity levels were similar between groups. Lower insulin sensitivity in AAW was not explained by total or central adiposity. Skeletal muscle triglyceride content was similar, but mitochondrial content was lower in AAW. Mitochondrial respiration was 24% lower in AAW and correlated with skeletal muscle insulin sensitivity (r = 0.33, P < .05)., Conclusion: When compared with CW, AAW have similar hepatic insulin sensitivity but a muscle phenotype characterized by both lower insulin sensitivity and lower mitochondrial oxidative capacity. These observations occur in the absence of obesity and are not explained by physical activity. The only factor associated with lower insulin sensitivity in AAW was mitochondrial oxidative capacity. Because exercise training improves both mitochondrial capacity and insulin sensitivity, we suggest that it may be of particular benefit as a strategy for diabetes prevention in AAW.

Background & Aims: Acute pancreatitis (AP) and chronic pancreatitis (CP) share etiologies, but AP can be more severe and is associated with a higher rate of mortality. We investigated features of CP that protect against severe disease. The amount of intrapancreatic fat (IPF) is increased in obese patients and fibrosis is increased in patients with CP, so we studied whether fibrosis or fat regulate severity of AP attacks in patients with CP., Methods: We reviewed records from the University of Pittsburgh Medical Center/Presbyterian Hospital Autopsy Database (1998-2008) for patients with a diagnosis of AP (n = 23), CP (n = 35), or both (AP-on-CP; n = 15). Pancreatic histology samples from these patients and 50 randomly selected controls (no pancreatic disease) were analyzed, and IPF data were correlated with computed tomography data. An adipocyte and acinar cell Transwell coculture system, with or without collagen type I, was used to study the effects of fibrosis on acinar-adipocyte interactions. We studied the effects of nonesterified fatty acids (NEFAs) and adipokines on acinar cells in culture., Results: Levels of IPF were significantly higher in nonobese patients with CP than in nonobese controls. In patients with CP or AP-on-CP, areas of IPF were surrounded by significantly more fibrosis than in controls or patients with AP. Fat necrosis-associated peri-fat acinar necrosis (PFAN, indicated by NEFA spillage) contributed to most of the necrosis observed in samples from patients with AP; however, findings of peri-fat acinar necrosis and total necrosis were significantly lower in samples from patients with CP or AP-on-CP. Fibrosis appeared to wall off the fat necrosis and limit peri-fat acinar necrosis, reducing acinar necrosis. In vitro, collagen I limited the lipolytic flux between acinar cells and adipocytes and prevented increases in adipokines in the acinar compartment. This was associated with reduced acinar cell necrosis. However, NEFAs, but not adipokines, caused acinar cell necrosis., Conclusions: Based on analysis of pancreatic samples from patients with CP, AP, or AP-on-CP and in vitro studies, fibrosis reduces the severity of acute exacerbations of CP by reducing lipolytic flux between adipocytes and acinar cells., (Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Epidemiologic studies have suggested that most cases of sporadic colon cancer can be attributed to diet. The recognition that colonic microbiota have a major influence on colonic health suggests that they might mediate colonic carcinogenesis., Objective: To examine the hypothesis that the influence of diet on colon cancer risk is mediated by the microbiota through their metabolites, we measured differences in colonic microbes and their metabolites in African Americans with a high risk and in rural native Africans with a low risk of colon cancer., Design: Fresh fecal samples were collected from 12 healthy African Americans aged 50-65 y and from 12 age- and sex-matched native Africans. Microbiomes were analyzed with 16S ribosomal RNA gene pyrosequencing together with quantitative polymerase chain reaction of the major fermentative, butyrate-producing, and bile acid-deconjugating bacteria. Fecal short-chain fatty acids were measured by gas chromatography and bile acids by liquid chromatography-mass spectrometry., Results: Microbial composition was fundamentally different, with a predominance of Prevotella in native Africans (enterotype 2) and of Bacteroides in African Americans (enterotype 1). Total bacteria and major butyrate-producing groups were significantly more abundant in fecal samples from native Africans. Microbial genes encoding for secondary bile acid production were more abundant in African Americans, whereas those encoding for methanogenesis and hydrogen sulfide production were higher in native Africans. Fecal secondary bile acid concentrations were higher in African Americans, whereas short-chain fatty acids were higher in native Africans., Conclusion: Our results support the hypothesis that colon cancer risk is influenced by the balance between microbial production of health-promoting metabolites such as butyrate and potentially carcinogenic metabolites such as secondary bile acids.

Objective: Obesity increases cardiovascular disease risk and adversely affects vascular structure and function. Few studies have evaluated the vascular effects of non-surgical weight reduction in the severely obese. We hypothesized that weight loss and improvements in cardiometabolic factors would reduce common carotid artery intima-media thickness (CIMT) and inter-adventitial diameter (AD) in severely obese adults., Methods: We performed carotid ultrasound and measured cardiometabolic factors in 90 severely obese participants (body mass index (BMI)≥35 kg/m(2), age 30-55) at baseline and 6 months in a randomized clinical trial of dietary intervention with (n=45) or without (n=45) physical activity., Results: The achieved weight loss (mean=8%) did not differ significantly by intervention group (P=0.10) and resulted in a 0.07 mm mean decrease in AD (P=0.001). AD change was positively correlated with changes in BMI, waist circumference, abdominal visceral and subcutaneous fat, and body fat mass, and AD decreased more in men (P<0.05 for all). After multivariable adjustment, changes in BMI (P=0.03) and abdominal subcutaneous fat (P=0.04) were significant determinants of AD change. Although CIMT did not decrease significantly overall (-0.008 mm, P=0.16), individuals who lost at least 5% of their body weight experienced a significant mean reduction in CIMT of 0.02 mm (P=0.002). CIMT change was positively correlated with changes in BMI, waist circumference, fat-free mass, leptin, and insulin (P<0.05 for all). After multivariable adjustment, insulin reduction remained a significant determinant of CIMT decrease (P=0.03)., Conclusion: A 6 month intensive behavioral intervention can significantly reverse metabolic and vascular abnormalities in severely obese adults., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Although investigators have been engaged in the study of human energy metabolism for over 100 years, there remain unanswered questions regarding the role that energy expenditure plays in human health and disease. A critical examination of available methods for measurement of the various components of daily energy expenditure is presented. Using a combination of the techniques available today, each component can be reliably studied, and the role that each of these plays in the human health can be examined. Several examples of the application of energy expenditure methods are presented. Finally, data are presented describing current knowledge regarding the relation between energy metabolism and cancer, including cancer risk, response to cancer, and in cancer survivors., (Copyright © 2011 Wiley Periodicals, Inc.)

Aim: To determine tolerance to fiber supplementation of semi-elemental tube feeds in critically ill patients and measure its effect on colonic microbiota and fermentation., Methods: Thirteen intensive care unit patients receiving jejunal feeding with a semi-elemental diet for predominantly necrotizing pancreatitis were studied. The study was divided into 2 parts: first, short-term (3-9 d) clinical tolerance and colonic fermentation as assessed by fecal short chain fatty acid (SCFA) concentrations and breath hydrogen and methane was measured in response to progressive fiber supplementation increasing from 4 g tid up to normal requirement levels of 8 g tid; second, 4 patients with diarrhea were studied for 2-5 wk with maximal supplementation to additionally assess its influence on fecal microbiota quantitated by quantitative polymerase chain reaction (qPCR) of microbial 16S rRNA genes and Human Intestinal Tract Chip (HITChip) microarray analysis. Nearly all patients were receiving antibiotics (10/13) and acid suppressants (11/13) at some stage during the studies., Results: In group 1, tolerance to progressive fiber supplementation was good with breath hydrogen and methane evidence (P = 0.008 and P < 0.0001, respectively) of increased fermentation with no exacerbation of abdominal symptoms and resolution of diarrhea in 2 of 4 patients. In group 2 before supplementation, fecal microbiota mass and their metabolites, SCFA, were dramatically lower in patients compared to healthy volunteers. From qPCR and HITChip analyses we calculated that there was a 97% reduction in the predominant potential butyrate producers and starch degraders. Following 2-5 wk of fiber supplementation there was a significant increase in fecal SCFA (acetate 28.4 ± 4.1 μmol/g to 42.5 ± 3.1 μmol/g dry weight, P = 0.01; propionate 1.6 ± 0.5 vs 6.22 ± 1.1, P = 0.006 and butyrate 2.5 ± 0.6 vs 5.9 ± 1.1, P = 0.04) and microbial counts of specific butyrate producers, with resolution of diarrhea in 3 of 4 patients., Conclusion: Conventional management of critically ill patients, which includes the use of elemental diets and broad-spectrum antibiotics, was associated with gross suppression of the colonic microbiota and their production of essential colonic fuels, i.e., SCFA. Our investigations show that fiber supplementation of the feeds has the potential to improve microbiota mass and function, thereby reducing the risks of diarrhea due to dysbiosis.

Context: The prevalence of severe obesity is increasing markedly, as is prevalence of comorbid conditions such as hypertension and type 2 diabetes mellitus; however, apart from bariatric surgery and pharmacotherapy, few clinical trials have evaluated the treatment of severe obesity., Objective: To determine the efficacy of a weight loss and physical activity intervention on the adverse health risks of severe obesity., Design, Setting, and Participants: Single-blind randomized trial conducted from February 2007 through April 2010 at the University of Pittsburgh. Participants were 130 (37% African American) severely obese (class II or III) adult participants without diabetes recruited from the community., Interventions: One-year intensive lifestyle intervention consisting of diet and physical activity. One group (initial physical activity) was randomized to diet and physical activity for the entire 12 months; the other group (delayed physical activity) had the identical dietary intervention but with physical activity delayed for 6 months., Main Outcome Measures: Changes in weight. Secondary outcomes were additional components comprising cardiometabolic risk, including waist circumference, abdominal adipose tissue, and hepatic fat content., Results: Of 130 participants randomized, 101 (78%) completed the 12-month follow-up assessments. Although both intervention groups lost a significant amount of weight at 6 months, the initial-activity group lost significantly more weight in the first 6 months compared with the delayed-activity group (10.9 kg [95% confidence interval {CI}, 9.1-12.7] vs 8.2 kg [95% CI, 6.4-9.9], P = .02 for group × time interaction). Weight loss at 12 months, however, was similar in the 2 groups (12.1 kg [95% CI, 10.0-14.2] vs 9.9 kg [95% CI, 8.0-11.7], P = .25 for group × time interaction). Waist circumference, visceral abdominal fat, hepatic fat content, blood pressure, and insulin resistance were all reduced in both groups. The addition of physical activity promoted greater reductions in waist circumference and hepatic fat content., Conclusion: Among patients with severe obesity, a lifestyle intervention involving diet combined with initial or delayed initiation of physical activity resulted in clinically significant weight loss and favorable changes in cardiometabolic risk factors., Trial Registration: clinicaltrials.gov Identifier: NCT00712127.

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 +/- 18.8 y (mean +/- SD) were analyzed in linear regression models with natural log (ln) weight as the dependent variable and ln 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: ln EnFlux was positively related to ln weight (beta = 0.71; 95% CI: 0.66, 0.76; R2 = 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: We tested the hypothesis that ad libitum food intake shows corrective responses over periods of 1-5 d., Design: This was a prospective study of food intake in women., Methods: Two methods, a weighed food intake and a measured food intake, were used to determine daily nutrient intake during 2 wk in 20 women. Energy expenditure with the use of doubly labeled water was done contemporaneously with the weighed food-intake record. The daily deviations in macronutrient and energy intake from the average 7-d values were compared with the deviations observed 1, 2, 3, 4, and 5 d later to estimate the corrective responses., Results: Both methods of recording food intake gave similar patterns of macronutrient and total energy intakes and for deviations from average intakes. The intraindividual CVs for energy intake ranged from +/-12% to +/-47% with an average of +/-25%. Reported energy intake was 85.5-95.0% of total energy expenditure determined by doubly labeled water. Significant corrective responses were observed in food intakes with a 3- to 4-d lag that disappeared when data were randomized within each subject., Conclusions: Human beings show corrective responses to deviations from average energy and macronutrient intakes with a lag time of 3-4 d, but not 1-2 d. This suggests that short-term studies may fail to recognize important signals of food-intake regulation that operate over several days. These corrective responses probably play a crucial role in bringing about weight stability.

Overweight and obesity have become an epidemic in many parts of the world threatening the health of over one billion people. In order to combat this epidemic effectively, it is desirable to develop new methods to monitor individual's food intake and provide quantitative information about the nutrients and calories consumed in people's daily life. We present an electronic photographic approach and associated image processing algorithms to estimate food portion size, which is then utilized to obtain the required information. Our experiments show that our approach is accurate, providing an effective tool for people to track their nutritional and energy intake.

Background: There remains no consensus about the optimal dietary composition for sustained weight loss., Objective: The objective was to examine the effects of 2 dietary macronutrient patterns with different glycemic loads on adherence to a prescribed regimen of calorie restriction (CR), weight and fat loss, and related variables., Design: A randomized controlled trial (RCT) of diets with a high glycemic load (HG) or a low glycemic load (LG) at 30% CR was conducted in 34 healthy overweight adults with a mean (+/-SD) age of 35 +/- 6 y and body mass index (kg/m(2)) of 27.6 +/- 1.4. All food was provided for 6 mo in diets controlled for confounding variables, and subjects self-administered the plans for 6 additional months. Primary and secondary outcomes included energy intake measured by doubly labeled water, body weight and fatness, hunger, satiety, and resting metabolic rate., Results: All groups consumed significantly less energy during CR than at baseline (P < 0.01), but changes in energy intake, body weight, body fat, and resting metabolic rate did not differ significantly between groups. Both groups ate more energy than provided (eg, 21% and 28% CR at 3 mo and 16% and 17% CR at 6 mo with HG and LG, respectively). Percentage weight change at 12 mo was -8.04 +/- 4.1% in the HG group and -7.81 +/- 5.0% in the LG group. There was no effect of dietary composition on changes in hunger, satiety, or satisfaction with the amount and type of provided food during CR., Conclusions: These findings provide more detailed evidence to suggest that diets differing substantially in glycemic load induce comparable long-term weight loss.

Background: Clinical trials involving calorie restriction (CR) require an assessment of adherence to a prescribed CR with the use of an objective measure of energy intake (EI)., Objective: The objective was to validate the use of energy expenditure (EE) measured by doubly labeled water (DLW), in conjunction with precise measures of body composition, to calculate an individual's EI during 30% CR., Design: Ten participants underwent 30% CR for 3 wk. During the last week (7 d), 24-h EE was measured in a respiratory chamber and simultaneously by DLW (EEDLW). EI was calculated from 7-d EE measured by DLW and from changes in energy stores (ES) (weight and body composition). Calculated EI was then compared with the actual EI measured in the chamber by using the following equations: calculated EI (kcal/d) = EEDLW + DeltaES, where DeltaESFM/FFM (kcal/d) = (9.3 x DeltaFM, g/d) + (1.1 x DeltaFFM, g/d), FM is fat mass, and FFM is fat-free mass., Results: We found close agreement (R = 0.88) between EE measured in the metabolic chamber and EEDLW during CR. Using the measured respiratory quotient, we found that the mean (+/-SD) EE(DLW) was 1934 +/- 377 kcal/d and EE measured in the metabolic chamber was 1906 +/- 327 kcal/d, ie, a 1.3 +/- 8.9% overestimation. EI calculated from EEDLW and from changes in ES was 8.7 +/- 36.7% higher than the actual EI provided during the chamber stay (1596 +/- 656 kcal/d)., Conclusions: DLW methods can accurately estimate 24-h EE during CR. Although the mean difference between actual and calculated EIs for the group was small, we conclude that the interindividual variability was too large to provide an assessment of CR adherence on an individual basis.

Background: The hypothesis that alterations in energy metabolism predict body fat gain is controversial., Objective: The aim of this study was to determine which components of energy metabolism were most important in predicting fat gain in children aged 10.8 +/- 0.6 y., Design: A 2-y longitudinal study to examine whether components of energy metabolism are predictors of body fat gain was conducted in 114 preadolescent African American and white children aged 9-11 y by measuring total daily energy expenditure on the basis of doubly labeled water (DLW), resting metabolic rate, the thermic effect of food, energy expended in physical activity, and substrate oxidation after a meal. The primary endpoint was the 2-y change in percentage body fat (%BF)., Results: Individual variables of energy metabolism predicted up to 7% of the variance in changes in %BF over the 2-y interval in the whole group. Predictors of change in body fatness tended to be sex and race specific. Protein oxidation during a test meal explained a significant portion of the variance in change in %BF in the overall group and in nearly all of the subgroups. Multivariate prediction models accounted for 10-41% of the variance in change in %BF. Tanner stage at 2-y follow-up was highly predictive of change in body fatness and improved the overall prediction, accounting for 24-62% of the variance in change in %BF in those groups in which Tanner entered the model., Conclusion: This study provides evidence that total daily energy expenditure, resting metabolic rate, substrate oxidation, and total energy intake are predictors of gain in body fatness during late childhood in boys and girls.

Background: A challenging 7-d ranger field exercise (FEX) by cadets in the Norwegian Military Academy provided a venue in which to study the effects of negative energy balance., Objective: We quantified total energy expenditure (TEE), food intake, and changes in body composition in male and female cadets., Design: TEE (measured by doubly labeled water), food intake, activity patterns (measured by accelerometry), and body composition (measured by dual-energy X-ray absorptiometry) were measured in 16 cadets (10 men and 6 women aged 21-27 y)., Results: The physically active (approximately 23 h/d) and semistarved (0.2-2.2 MJ/d) cadets lost weight (x +/- SD: men, -7.7 +/- 1.1 kg; women, -5.9 +/- 1.1 kg; P < 0.05). Absolute TEE differed by sex (men, 26.6 +/- 2.0 MJ/d; women, 21.9 +/- 2.0 MJ/d; P < 0.05) but body weight-specific TEE did not (men, 343 +/- 26 kJ . kg(-1) . d(-1); women, 354 +/- 18 kJ . kg(-1) . d(-1); NS). Fat-free mass (FFM) loss differed significantly by sex (men, -4.0 +/- 1.2 kg; women, -2.5 +/- 1.1 kg; P < 0.05), but percentage FFM loss did not (men, -6.3 +/- 1.9%; women, -5.6 +/- 2.4%). In contrast, absolute FM loss did not differ significantly by sex (men, -3.45 +/- 0.72 kg; women, -3.42 +/- 0.22 kg), but fat oxidation (men, 5.2 +/- 1.0 mg . min(-1) . kg FFM(-1); women, 7.3 +/- 0.5 mg . min(-1) . kg FFM(-1)) and the relative contribution of FM to TEE (men, 74 +/- 14%; women, 89 +/- 6%) were significantly greater in women than in men (P < 0.05)., Conclusion: Female cadets maintained a significantly more fat-predominant fuel metabolism than did male cadets in response to sustained exercise and semistarvation.

Unlabelled: Fifty U.S. Marine recruits (30 men, 20 women) were studied during a physically intense, energy intake-restricted, winter-time 54-h field training exercise (FEX) at Parris Island Marine Corps Recruit Depot. Men and women completed the same physical tasks., Purpose: To characterize and compare the total energy expenditure (TEE) and core temperature responses in men and women working almost continuously for 2.25 d in an outdoor environment while developing a substantial energy deficit., Methods: TEE was measured using doubly labeled water (D(2)O(18)). Energy intake was estimated using beverage diaries and collecting ration wrappers saved by each volunteer and adding the known caloric value of each food item consumed. Core temperature was measured using an ingested thermometer pill. Physical activity level (PAL) was calculated by dividing TEE by the calculated basal metabolic rate., Results: TEE was higher (P < 0.001) for the men (25.7 MJ.d(-1)) than women (19.8 MJ.d(-1)), but there were no differences between men and women in TEE normalized to body mass (men, 0.35 +/- 0.05 MJ.d(-1).kg(-1); women, 0.34 +/- 0.06 MJ.d(-).kg(-1)), corrected body mass (men, 0.29 +/- 0.04 MJ.d(-1).kg(-1) corrected body mass; women, 0.27 +/- 0.04 MJ.d(-1).kg(-1) corrected body mass), fat-free mass (men, 0.41 +/- 0.07 MJ.d(-1).kg(-1) FFM; women, 0.46 +/- 0.07 MJ.d(-1).kg(-1) FFM), or corrected fat-free mass (men, 0.30 +/- 0.05 MJ.d(-1).kg corrected body mass; women, 0.30 +/- 0.04 0.30 +/- 0.05 MJ.d(-1).kg(-1) corrected body mass). PAL was the same for men (3.4 +/- 0.5) and women (3.3 +/- 0.4). Energy intakes were higher (P < 0.05) in men (6.0 +/- 2.0 MJ.d(-1)) than women (4.8 +/- 1.8 MJ.d(-1)). The average minimum core temperature was 36.0 +/- 0.4 degrees C, and the mean maximum core temperature was 38.5 +/- 0.3 degrees C., Conclusions: For both men and women, total energy expenditures were among the highest observed for a military FEX. TEE, when normalized or corrected to body mass and fat-free mass, and PAL were the same for men and women.

Trans-fatty acids have been implicated as a risk factor for cardiovascular disease and diabetes. In addition, a polymorphism at codon 54 (Ala54Thr) in the fatty acid-binding protein 2 (FABP2) gene has been suggested to modify an interaction between dietary fat and insulin sensitivity. We examined the postprandial metabolic profiles after meals enriched with C18:1trans- relative to a similar meal with C18:1cis-fatty acid in individuals who were either FABP2 Ala54 homozygotes or Thr54 carriers. Moderately overweight men and women ate 2 breakfast test meals, separated by 1 week, each providing 40% of their daily energy requirement and containing 50% of energy as fat. In one meal, 10% of energy was from C18:1trans, and in the other meal, the C18:1trans was replaced with C18:1cis. Metabolic parameters were assessed during an 8-hour period. Insulin and C-peptide levels increased more after the C18:1trans meal, and this was associated with a greater fall in free fatty acids. Postprandial glucose levels and oxidation of fatty acids and carbohydrate were not different between the 2 test meals. The Thr54 allele for FABP2 increased the rise in postprandial glucose but not triacylglycerols. Fractional triacylglycerol synthetic rates were higher after consumption of the C18:1trans meal relative to the C18:1cis meal only in Thr54 carriers. These data show that a single meal enriched with C18:1trans-fatty acids can significantly increase insulin resistance, and that in the presence of the FABP2 Thr54 allele, may contribute to increased partitioning of glucose to triacylglycerols and insulin resistance.

The association of age and weekly swim training distance with body water, lean tissue, fat mass and regional adiposity was examined in 27 male masters swimmers. Subjects ranged in age from 25.3 to 73.1 years (mean age = 47.7 ± 11.1 years). Weekly swim distances, estimated from self-reported swim logs, were from 3 400 to 17 500 m and averaged 10 016 ± 4 223 m. Total body water (TBW), and extracellular water (ECW) were predicted from multi-frequency bioelectrical impedance analysis and intracellular water was estimated by difference. Lean soft tissue, bone mineral content, fat mass, and percent body fat were estimated from dual-energy X-ray absorptiometry. Measures of skinfold thickness, waist circumference, and abdominal sagittal diameter provided an indication of regional adiposity. Total body water, ECW, and ICW mean values (ranges) were as follows: 47.4 ± 4.6 L (37.9-56.9 L), 19.6 ± 1.8 L., (16.4-24.8 L), and 27.8 ± 3.2 L (21.5-34.4 L). Mean percent body fat levels were 21.9 ± 6.6% and ranged from 10.3 to 34.9%. Age was negatively associated with ICW (p = 0.02) and with the ICW/TBW ratio (p = 0.00). Multiple-linear regression analysis backward method suggested that both lean tissue and fat mass were predictors of ICW although the association with fat mass did not reach statistical significance (p = 0.00 and p = 0.06 for lean and fat mass respectively). There was a tendency for greater lower abdominal thickness with increasing age (p = 0.08), but no other associations were observed between age or with swimming and body composition variables. Changes in ICW and the ration of ICW to TBW appeared to be the strongest marker of aging in this group of adult male competitive swimmers. Key PointsSubject age was negatively associated with the volume of intracellular water and with the intracellular-to-total body water ratio.There was a trend for age to be positively related to lower abdominal thickness.Weekly swim training distance was not associated with body water, lean tissue, fat mass or regional adiposity.Lean tissue mass appeared to be a strong positive predictor of total body water and the intra- and extracellular fractions.There was a trend for fat mass to be a negative predictor of intracellular water volume.

Introduction: Survivors awaiting rescue aboard a disabled submarine (DISSUB) lacking power and/or environmental control would potentially be exposed to cold and reduced O2 and elevated CO2 levels. We hypothesized that elevated CO2 levels would lead to hormone changes that would mitigate cold and hypoxia-induced body fluid losses., Methods: Blood was drawn from seven men on three mornings: baseline (21% O2, 0.05% CO2), after 4 d of low O2, cold, and high CO2 (T101; 4 degrees C, 16.75% O2, 2.5% CO2), and following acute withdrawal of cold and high CO2 (T173, 16.75% O2, 0.05% CO2). Total body water (TBW) was measured using deuterium oxide dilution at baseline and at T148. Hormone analyses included atrial natriuretic peptide (ANP), aldosterone (ALDO), and plasma renin activity (PRA)., Results: TBW decreased by 0.4 +/- 0.4 L. Water turnover was 3.0 +/- 0.5 L x d(-1). ANP (pg x ml(-1)) was lower (p < 0.05) at T101 (3.46 +/- 1.17) and T173 (4.97 +/- 2.28) vs. baseline (8.19 +/- 3.40). PRA (pg x ml(-1)) was higher (p < 0.05) at T101 (10.43 +/- 4.90) and T173 (14.23 +/- 4.48) vs. baseline (6.81 +/- 3.43). ALDO, serum osmolality, and electrolytes were not different across time. Urine flow was lower at T101 and T173 vs. baseline, and urine osmotic clearance was lower at T173 vs. baseline. Free water clearance did not change across time., Discussion: These data indicate that the combination of cold, low O2, and high CO2 for 5-7 d did not change total body water and hormone changes and urinary measures across the DISSUB were consistent with fluid retention.

Adipogenesis plays a critical role in energy metabolism and is a contributing factor to the obesity epidemic. This study examined the proteome of primary cultures of human adipose-derived adult stem (ADAS) cells as an in vitro model of adipogenesis. Protein lysates obtained from four individual donors were compared before and after adipocyte differentiation by two-dimensional gel electrophoresis and tandem mass spectroscopy. Over 170 individual protein features in the undifferentiated adipose-derived adult stem cells were identified. Following adipogenesis, over 40 proteins were up-regulated by > or = 2-fold, whereas 13 showed a > or = 3-fold reduction. The majority of the modulated proteins belonged to the following functional categories: cytoskeleton, metabolic, redox, protein degradation, and heat shock protein/chaperones. Additional immunoblot analysis documented the induction of four individual heat shock proteins and confirmed the presence of the heat shock protein 27 phosphoserine 82 isoform, as predicted by the proteomic analysis, as well as the crystallin alpha phosphorylated isoforms. These findings suggest that the heat shock protein family proteome warrants further investigation with respect to the etiology of obesity and type 2 diabetes.

Background: Total energy expenditure (TEE) assessment using pedometers provide an easy and less expensive method than doubly labeled water (DLW). This study assessed TEE by a new pedometry method (TEEpedo) compared to the doubly labeled water method (TEEdlw)., Material/methods: Shipboard sailors (7 men, age: 23.0+/-3.9 yrs; ht: 180.2+/-6.5 cm; wt: 83.8+/-11.8 kg, and 10 women, age: 24.7+/-4.4 yrs; ht: 165.2+/-8.0 cm; wt: 63.5+/-14.0 kg) (Mean +/-SD) were studied for 8 days. The energy cost of activity was estimated using (a) total body weight, (b) foot-ground contact times [Tc] during running, walking, and non-exercise activity [NEAT], and (c) the known proportion of time spent in each activity category. Resting metabolic rate (RMR) was estimated from lean body mass., Results: TEEPEDO was calculated as: TEEpedo (MJ) = (1440 x [%Run Time x ((0.0761 x [Total Body Weight/TcRun]) - 7.598) +%Walk Time x ((0.056 x [Total Body Weight/TcWalk]) - 2.938) + (%NEAT Time x 0.1 x [RMR/Minute])] + RMR)/239. This method, explained 79% of the variance of TEEpedo with a 95% confidence interval of +/-0.81 MJ/day, relative to TEEdlw (12.55+/-3.3MJ/day). Mean TEEpedo (12.65+/-3.1 MJ/day) did not differ from mean TEEdlw (p=0.95)., Conclusions: At TEEs >14 MJ/day, the TEEpedo method underestimated actual TEE, possibly due to unaccounted for upper body exercise. At more moderate TEEs of 9 to 14 MJ/day, the Tc pedometry method provided accurate estimates of TEE.

Background: Accurate estimation of children's resting energy expenditure (REE) is important for planning dietary therapy., Objective: Our objective was to compare the utility of 5 REE prediction equations in a diverse sample of young children., Design: REE was obtained in 502 black and white girls and boys aged 6-11 y by using indirect calorimetry at 4 US sites. Measured REE and REE predicted from the equations were compared., Results: None of the equations provided both accurate and unbiased estimates of REE. Two new sets of sex-specific equations including race as a factor were generated and evaluated. One set used easily measured variables-females: REE = 0.046 x weight - 4.492 x 1/height(2) - 0.151 x race + 5.841; males: REE = 0.037 x weight - 4.67 x 1/height(2) - 0.159 x race + 6.792-and accounted for 72% and 69%, respectively, of REE variance. The other set used body-composition variables-females: REE = 0.101 x fat-free mass + 0.025 x fat mass + 0.293 x height(3) - 0.185 x race + 1.643; males: REE = 0.078 x fat-free mass + 0.026 x fat mass - 2.646 x 1/height(2) - 0.244 x race + 4.8-and accounted for 75% and 71%, respectively, of REE variance. When split by race and adiposity, the small bias generated could be corrected to within 0.25 MJ (60 kcal) of the mean measured value., Conclusion: Sex-specific equations must take race into account to predict REE adequately in children.