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Background: A metabolic adaptation, defined as an increase in energy expenditure (EE) beyond what is expected with weight gain during overfeeding (OF), has been reported but also refuted. Much of the inconsistency stems from the difficulty in conducting large, well-controlled OF studies in humans., Objectives: The primary aim of this study was to determine whether a metabolic adaptation to OF exists and if so, attenuates weight gain., Methods: Thirty-five young adults consumed 40% above their baseline energy requirements for 8 wk, and sleeping metabolic rate (SMR) and 24-h sedentary energy expenditure (24h-EE) were measured before and after OF. Subjects were asked to return for a 6-mo post-OF follow-up visit to measure body weight, body composition, and physical activity., Results: After adjusting for gains in fat-free mass and fat mass, SMR increased by 43 ± 123 kcal/d more than expected (P = 0.05) and 24h-EE by 23 ± 139 kcal/d (P = 0.34), indicating an overall lack of metabolic adaptation during OF despite a wide variability in the response. Among the 30 subjects who returned for the 6-mo follow-up visit, those who had a lower-than-predicted SMR (basal EE) retained more of the fat gained during OF. Likewise, subjects displaying a higher-than-predicted sedentary 24h-EE lost significantly more fat during the 6-mo follow-up., Conclusions: Metabolic adaptation to OF was on average very small but variable between subjects, revealing "thrifty" or "spendthrift" metabolic phenotypes related to body weight loss 6 mo later. This trial was registered at clinicaltrials.gov as NCT01672632., (Copyright © American Society for Nutrition 2019.)

Aims/hypotheses: Reduced mitochondrial capacity in skeletal muscle has been observed in obesity and type 2 diabetes. In humans, the aetiology of this abnormality is not well understood but the possibility that it is secondary to the stress of nutrient overload has been suggested. To test this hypothesis, we examined whether sustained overfeeding decreases skeletal muscle mitochondrial content or impairs function., Methods: Twenty-six healthy volunteers (21 men, 5 women, age 25.3 ± 4.5 years, BMI 25.5 ± 2.4 kg/m 2 ) underwent a supervised protocol consisting of 8 weeks of high-fat overfeeding (40% over baseline energy requirements). Before and after overfeeding, we measured systemic fuel oxidation by indirect calorimetry and performed skeletal muscle biopsies to measure mitochondrial gene expression, content and function in vitro. Mitochondrial function in vivo was measured by 31 P NMR spectroscopy., Results: With overfeeding, volunteers gained 7.7 ± 1.8 kg (% change 9.8 ± 2.3). Overfeeding increased fasting NEFA, LDL-cholesterol and insulin concentrations. Indirect calorimetry showed a shift towards greater reliance on lipid oxidation. In skeletal muscle tissue, overfeeding increased ceramide content, lipid droplet content and perilipin-2 mRNA expression. Phosphorylation of AMP-activated protein kinase was decreased. Overfeeding increased mRNA expression of certain genes coding for mitochondrial proteins (CS, OGDH, CPT1B, UCP3, ANT1). Despite the stress of nutrient overload, mitochondrial content and mitochondrial respiration in muscle did not change after overfeeding. Similarly, overfeeding had no effect on either the emission of reactive oxygen species or on mitochondrial function in vivo., Conclusions/interpretation: Skeletal muscle mitochondria are significantly resilient to nutrient overload. The lower skeletal muscle mitochondrial oxidative capacity in human obesity is likely to be caused by reasons other than nutrient overload per se., Trial Registration: ClinicalTrials.gov NCT01672632.

Objective: Intramyocellular lipid (IMCL) is inversely related to insulin sensitivity in sedentary populations, yet no prospective studies in humans have examined IMCL accumulation with overfeeding., Methods: Twenty-nine males were overfed a high-fat diet (140% caloric intake, 44% from fat) for 8 weeks. Measures of IMCL, whole-body fat oxidation from a 24-hour metabolic chamber, muscle protein extracts, and muscle ceramide measures were obtained before and after the intervention., Results: Eight weeks of overfeeding did not increase overall IMCL. The content of smaller lipid droplets peripherally located in the myofiber decreased, while increases in larger droplets correlated inversely with glucose disposal rate. Overfeeding resulted in inhibition of Akt activity, which correlated with the reductions in smaller, peripherally located lipid droplets and drastic increases in ceramide content. Additionally, peripherally located lipid droplets were associated with more efficient lipid oxidation. Finally, participants who maintained a greater number of smaller, peripherally located lipid droplets displayed a better resistance to weight gain with overfeeding., Conclusions: These results show that lipid droplet size and location rather than mere IMCL content are important to understanding insulin sensitivity., (© 2017 The Obesity Society.)

Background/objective: Impairments in metabolic flexibility (MF) and substrate handling are associated with metabolic syndrome. However, it is unknown whether metabolic inflexibility causes insulin resistance. We therefore measured MF and substrate handling before and after 8 weeks of overfeeding in initially healthy adults as a model of the early stages of insulin resistance., Subjects/methods: Twenty-nine healthy men (27±5 years old; body mass index 25.5±2.3 kg m -2 ) were overfed by 40% above baseline energy requirements for 8 weeks and gained 7.6±2.1 kg of weight. Before and after overfeeding, energy expenditure, substrate oxidation and MF were measured in two ways: (a) during 1 day of eucaloric feeding in a whole-room indirect calorimeter and (b) during a two-step hyperinsulinemic-euglycemic clamp., Results: Eight weeks of overfeeding decreased insulin sensitivity at low and high doses of insulin (P=0.001 and P=0.06, respectively). This was accompanied by decreases in the respiratory quotient (RQ) while sleeping (from 0.877±0.020 to 0.864±0.026; P=0.05) and at low insulin levels during the clamp (from 0.927±0.047 to 0.907±0.032; P=0.01). Overfeeding did not affect MF as measured during a clamp (P⩾0.17), but it tended to increase 24-h MF (awake RQ-sleep RQ) as measured by chamber by 0.010±0.028 (P=0.08). In terms of substrate oxidation, overfeeding increased protein oxidation by 13±23 g day -1 (P=0.003) and tended to increase fat oxidation by 6±16 g day -1 (P=0.07) but did not affect carbohydrate oxidation (P=0.64). Individuals with greater metabolic adaptation to overfeeding had higher carbohydrate oxidation rates (r=0.66, P=8 × 10 -5 ) but not fat oxidation rates (P=0.09)., Conclusions: The early stages of insulin resistance are accompanied by modest declines in the RQs during sleep and during a clamp, with no changes in fasting RQ or signs of metabolic inflexibility. Our data therefore suggest that metabolic inflexibility does not cause insulin resistance.

Objective: To evaluate the effectiveness of a weight loss intervention in Mongolian adults with newly diagnosed type 2 diabetes mellitus and with BMIs ≥ 25.0 kg/m 2 ., Methods: Eighty participants (33 men/47 women) aged 32-56 years old received education sessions to improve nutritional habits and increase physical activity. Participants were counselled in-person on two occasions with regular follow-up by phone to eat less (reduce calorie intake by 30-40% and consume fewer fatty foods), shift food intake to earlier in a day and increase physical activity such as walking, jogging, running and biking. Measurements were performed before and after the 6-month intervention., Results: After 6 months, the average weight loss was 4.3 ± 4.7 kg, representing a 4.9 ± 5.4% reduction in body weight ( p  < 0.0001). Mean HbA1c decreased from 8.5 ± 2.7% to 6.0 ± 1.8% ( p  < 0.0001), and the percent of individuals with HbA1c in the diabetic range dropped from 76.3% to 27.5%. These changes were accompanied by marked improvements in cardiovascular risk factors, including total cholesterol (3.92 ± 1.02 to 3.13 ± 0.80 mmol/l; p  < 0.0001) and triglycerides (2.11 ± 0.82 to 1.54 ± 0.51 mmol/l; p  < 0.0001), and modest reductions in systolic and diastolic blood pressure ( p  < 0.05)., Conclusion: The remarkable improvement in glycemic control and lipid profile in participants suggests that a lifestyle modification intervention targeting weight loss may be highly effective for early diabetes treatment and prevention in Mongolians.

Objective: Diabetic nephropathy is characterized at its onset by glomerular hyperfiltration. Prospective studies in humans measuring filtration rates with weight gain are lacking. We investigated renal filtration following weight gain induced by overfeeding., Design: Eight weeks of overfeeding (40% above energy requirements, 44% fat, 15% protein and 41% carbohydrate) as well as a 6-month follow-up after the overfeeding intervention., Subjects: Thirty-five participants (age: 26.7 ±5.3 years; body mass index: 25.5 ± 2.2 kg m(-2) ; 29 m/6f)., Measurements: Creatinine clearance rate (Ccr) from 24-h urine collection, estimated glomerular filtration rate (eGFR) from the modification of diet in renal disease (MDRD), insulin sensitivity/glucose disposal rate (GDR) by a euglycemic-hyperinsulinemic clamp, components from basic metabolic panels and serum lipid panels., Results: Both eGFR and Ccr increased with overfeeding (P = 0.04) and serum lipids (all P < 0.05), along with a decrease in insulin sensitivity (P = 0.003). Fasting glucose concentration was not affected (P = 0.98), but the per cent change in Ccr correlated positively with the change in GDR with overfeeding (r = 0.39, P = 0.02). Six months following overfeeding, serum glucose was maintained, and no evidence of urinary glucose was observed at any time-point., Conclusions: These data suggest that renal hyperfiltration may act as a mechanism to preserve insulin sensitivity through maintenance of systemic glucose homoeostasis with caloric excess., (© 2015 The Association for the Publication of the Journal of Internal Medicine.)

Objective: To measure changes in resting metabolic rate (RMR) and body composition in obese subjects following massive weight loss achieved via bariatric surgery or calorie restriction plus vigorous exercise., Methods: Body composition and RMR were measured in 13 pairs of obese subjects retrospectively matched for sex, body mass index, weight, and age who underwent either Roux-en-Y gastric bypass surgery (RYGB) or participated in "The Biggest Loser" weight loss competition (BLC)., Results: Both groups had similar final weight loss (RYGB: 40.2 ± 12.7 kg, BLC: 48.8 ± 14.9 kg; P = 0.14); however, RYGB lost a larger proportion of their weight as fat-free mass (FFM) (RYGB: 30 ± 12%, BLC: 16 ± 8% [P < 0.01]). In both groups, RMR decreased significantly more than expected based on measured body composition changes. The magnitude of this metabolic adaptation was correlated with the degree of energy imbalance (r = 0.55, P = 0.004) and the decrease in circulating leptin (r = 0.47, P = 0.02)., Conclusions: Calorie restriction along with vigorous exercise in BLC participants resulted in preservation of FFM and greater metabolic adaption compared to RYGB subjects despite comparable weight loss. Metabolic adaptation was related to the degree of energy imbalance and the changes in circulating leptin., (© 2014 The Obesity Society.)

Objective: The presence of large subcutaneous adipocytes in obesity has been proposed to be linked with insulin resistance and type 2 diabetes through the "adipose tissue expandability" hypothesis, which holds that large adipocytes have a limited capacity for expansion, forcing lipids to be stored in nonadipose ectopic depots (skeletal muscle, liver), where they interfere with insulin signaling. This hypothesis has, however, been largely formulated by cross-sectional findings and to date has not been prospectively demonstrated in the development of insulin resistance in humans., Research Design and Methods: Twenty-nine men (26.8 ± 5.4 years old; BMI 25.5 ± 2.3 kg/m(2)) were fed 40% more than their baseline requirement for 8 weeks. Before and after overfeeding, insulin sensitivity was determined using a two-step hyperinsulinemic-euglycemic clamp. Intrahepatic lipid (IHL) and intramyocellular lipid (IMCL) were measured by (1)H-MRS and abdominal fat by MRI. Subcutaneous abdominal adipose and skeletal muscle tissues were collected to measure adipocyte size and markers of tissue inflammation., Results: Subjects gained 7.6 ± 2.1 kg (55% fat) and insulin sensitivity decreased 18% (P < 0.001) after overfeeding. IHL increased 46% from 1.5% to 2.2% (P = 0.002); however, IMCL did not change. There was no association between adipocyte size and ectopic lipid accumulation. Despite similar weight gain, subjects with smaller fat cells at baseline had a greater decrease in insulin sensitivity, which was linked with upregulated skeletal muscle tissue inflammation., Conclusions: In experimental substantial weight gain, the presence of larger adipocytes did not promote ectopic lipid accumulation. In contrast, smaller fat cells were associated with a worsened metabolic response to overfeeding., (© 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)

Context: In animal models of obesity, chronic inflammation and dysregulated extracellular matrix remodeling in adipose tissue leads to insulin resistance. Whether similar pathophysiology occurs in humans is not clear., Objective: The aim of this study was to test whether 10% weight gain induced by overfeeding triggers inflammation and extracellular matrix remodeling (gene expression, protein, histology) in skeletal muscle and sc adipose tissue in humans. We also investigated whether such remodeling was associated with an impaired metabolic response (hyperinsulinemic-euglycemic clamp)., Design, Setting, Participants, and Intervention: Twenty-nine free-living males were fed 40% over their baseline energy requirements for 8 weeks., Results: Ten percent body weight gain prompted dramatic up-regulation of a repertoire of extracellular matrix remodeling genes in muscle and to a lesser degree in adipose tissue. The amount of extracellular matrix genes in the muscle were directly associated with the amount of lean tissue deposited during overfeeding. Despite weight gain and impaired insulin sensitivity, there was no change in local adipose tissue or systemic inflammation, but there was a slight increase in skeletal muscle inflammation., Conclusion: We propose that skeletal muscle extracellular matrix remodeling is another feature of the pathogenic milieu associated with energy excess and obesity, which, if disrupted, may contribute to the development of metabolic dysfunction.

Context: An important goal during weight loss is to maximize fat loss while preserving metabolically active fat-free mass (FFM). Massive weight loss typically results in substantial loss of FFM potentially slowing metabolic rate., Objective: Our objective was to determine whether a weight loss program consisting of diet restriction and vigorous exercise helped to preserve FFM and maintain resting metabolic rate (RMR)., Participants and Intervention: We measured body composition by dual-energy x-ray absorptiometry, RMR by indirect calorimetry, and total energy expenditure by doubly labeled water at baseline (n = 16), wk 6 (n = 11), and wk 30 (n = 16)., Results: At baseline, participants were severely obese (× ± SD; body mass index 49.4 ± 9.4 kg/m(2)) with 49 ± 5% body fat. At wk 30, more than one third of initial body weight was lost (-38 ± 9%) and consisted of 17 ± 8% from FFM and 83 ± 8% from fat. RMR declined out of proportion to the decrease in body mass, demonstrating a substantial metabolic adaptation (-244 ± 231 and -504 ± 171 kcal/d at wk 6 and 30, respectively, P < 0.01). Energy expenditure attributed to physical activity increased by 10.2 ± 5.1 kcal/kg.d at wk 6 and 6.0 ± 4.1 kcal/kg.d at wk 30 (P < 0.001 vs. zero)., Conclusions: Despite relative preservation of FFM, exercise did not prevent dramatic slowing of resting metabolism out of proportion to weight loss. This metabolic adaptation may persist during weight maintenance and predispose to weight regain unless high levels of physical activity or caloric restriction are maintained.

In addition to adipose tissue, recent studies suggest that skeletal muscle may also be a source of low-grade inflammation, particularly in inactive and/or overweight individuals. The aim of this study was to examine the presence of macrophages in skeletal muscle from obese subjects with type 2 diabetes (T2D) before and after a 9-month exercise program (vs. a non-exercising control group) (Study 1) and in young vs. elderly subjects (Study 2). In both studies, CD68(+) macrophages in vastus lateralis biopsies were determined by immunohistochemistry and inflammation gene expression measured. Macrophage content (%) was calculated by the number of macrophages per 100 muscle fibers. In Study 1, we found relatively low numbers (2-3%) of CD68(+) macrophages in skeletal muscle in obese T2D subjects (BMI = 37.3 ± 5.2 kg/m(2)), which were unchanged after a 9-month exercise program (P = 0.42). Similarly, in Study 2 (BMI = 27.1 ± 2.5 kg/m(2)), CD68(+) macrophages were relatively low in muscle (4-5%) and were not different between young and elderly individuals (P = 0.42). However, elderly subjects had twofold higher CD68 and CD206 gene expression (both P < 0.002) than young participants. In both studies, CD68(+) muscle macrophages were not associated with BMI. In conclusion, we found little evidence of macrophage accumulation in skeletal muscle in obese T2D subjects or in elderly individuals. A 9-month exercise program was not associated with a decrease in macrophage content.

AIMS: To elucidate if endothelial dysfunction is an early CV risk marker in obese men and women with prediabetes. STUDY DESIGN: Cross-sectional study. PLACE AND DURATION OF STUDY: Clinical Research Unit, Pennington Biomedical Research Center, Baton Rouge, LA. United States. METHODOLOGY: Overweight and obese status denotes an increasing adipose tissue burden which spills over into ectopic locations, including the visceral compartment, muscle and liver. Associated co-morbidities enhance cardiovascular (CV) risk. Endothelium which is the largest receptor-effector end-organ in our bodies, while responding to numerous physical and chemical stimuli maintains vascular homeostasis. Endothelial dysfunction (ED) is the initial perturbation, which precedes fatty streak known to initiate atherosclerosis: insidious process which often culminates as sudden catastrophic CV adverse event. Asymptomatic men and women; [n=42] coming in after an overnight fast had demographic, anthropometric, clinical chemistry and resting endothelial function [EF: increased test finger peripheral arterial tone (PAT) relative to control; expressed as relative hyperemia index (RHI)] assessments. RESULTS: Adults with desirable weight [n=12] and overweight [n=8] state, had normal fasting plasma glucose [Mean(SD)]: FPG [91.1(4.5), 94.8(5.8) mg/dL], insulin [INS, 2.3(4.4), 3.1(4.8) μU/ml], insulin sensitivity by homeostasis model assessment [HOMA-IR, 0.62(1.2), 0.80(1.2)] and desirable resting clinic blood pressure [SBP/DBP, 118(12)/74(5), 118(13)/76(8) mmHg]. Obese adults [n=22] had prediabetes [FPG, 106.5(3.5) mg/dL], hyperinsulinemia [INS 18.0(5.2) μU/ml], insulin resistance [HOMA-IR 4.59(2.3)], prehypertension [PreHTN; SBP/DBP 127(13)/81(7) mmHg] and endothelial dysfunction [ED; reduced RHI 1.7(0.3) vs. 2.4(0.3); all p<0.05]. Age-adjusted RHI correlated with BMI [r=-0.53; p<0.001]; however, BMI-adjusted RHI was not correlated with age [r=-0.01; p=0.89]. CONCLUSION: Endothelial dysfunction reflective of cardiometabolic changes in obese adults can be an early risk marker for catastrophic CV events.

Aging is characterized by a progressive loss of muscle mass and muscle strength. Declines in skeletal muscle mitochondria are thought to play a primary role in this process. Mitochondria are the major producers of reactive oxygen species, which damage DNA, proteins, and lipids if not rapidly quenched. Animal and human studies typically show that skeletal muscle mitochondria are altered with aging, including increased mutations in mitochondrial DNA, decreased activity of some mitochondrial enzymes, altered respiration with reduced maximal capacity at least in sedentary individuals, and reduced total mitochondrial content with increased morphological changes. However, there has been much controversy over measurements of mitochondrial energy production, which may largely be explained by differences in approach and by whether physical activity is controlled for. These changes may in turn alter mitochondrial dynamics, such as fusion and fission rates, and mitochondrially induced apoptosis, which may also lead to net muscle fiber loss and age-related sarcopenia. Fortunately, strategies such as exercise and caloric restriction that reduce oxidative damage also improve mitochondrial function. While these strategies may not completely prevent the primary effects of aging, they may help to attenuate the rate of decline.

The physiologic effects of triiodothyronine (T3) on metabolic rate are well-documented; however, the effects of thyroxine (T4) are less clear despite its wide-spread use to treat thyroid-related disorders and other non-thyroidal conditions. Here, we investigated the effects of acute (3-day) T4 supplementation on energy expenditure at rest and during incremental exercise. Furthermore, we used a combination of in situ and in vitro approaches to measure skeletal muscle metabolism before and after T4 treatment. Ten healthy, euthyroid males were given 200 µg T4 (levothyroxine) per day for 3 days. Energy expenditure was measured at rest and during exercise by indirect calorimetry, and skeletal muscle mitochondrial function was assessed by in situ ATP flux ((31)P MRS) and in vitro respiratory control ratio (RCR, state 3/state 4 rate of oxygen uptake using a Clark-type electrode) before and after acute T4 treatment. Thyroxine had a subtle effect on resting metabolic rate, increasing it by 4% (p = 0.059) without a change in resting ATP demand (i.e., ATP flux) of the vastus lateralis. Exercise efficiency did not change with T4 treatment. The maximal capacity to produce ATP (state 3 respiration) and the coupled state of the mitochondria (RCR) were reduced by approximately 30% with T4 (p = 0.057 and p = 0.04, respectively). Together, the results suggest that T4, although less metabolically active than T3, reduces skeletal muscle efficiency and modestly increases resting metabolism even after short-term supplementation. Our findings may be clinically relevant given the expanding application of T4 to treat non-thyroidal conditions such as obesity and weight loss.

Context: Aging is associated with insulin resistance and unfavorable changes in body composition including increased fat accumulation, particularly in visceral and ectopic depots. Recent studies suggest that skeletal muscle mitochondrial activity may underlie some age-associated metabolic abnormalities., Objective: Our objective was to measure mitochondrial capacity and coupling of the vastus lateralis muscle in elderly and young adults using novel in vivo approaches and relate mitochondrial activity to metabolic characteristics., Design: This was a cross-sectional study., Participants and Intervention: Fourteen sedentary young (seven males and seven females, 20-34 yr of age) and 15 sedentary elderly (seven males and eight females, 70-84 yr of age) nonobese subjects selected for similar body weight underwent measures of body composition by magnetic resonance imaging and dual-energy x-ray absorptiometry, oral glucose tolerance, and in vivo mitochondrial activity by (31)P magnetic resonance and optical spectroscopy. Muscle biopsy was carried out in the same muscle to measure mitochondrial content, antioxidant activity, fiber type, and markers of mitochondrial biogenesis., Results: Elderly volunteers had reduced mitochondrial capacity (P = 0.05) and a trend for decreased coupling efficiency (P = 0.08) despite similar mitochondrial content and fiber type distribution. This was accompanied by greater whole-body oxidative stress (P = 0.007), less skeletal muscle mass (P < 0.001), more adipose tissue in all depots (P ≤ 0.002) except intramyocellular (P = 0.72), and lower glucose tolerance (P = 0.07)., Conclusions: Elderly adults show evidence of altered mitochondrial activity along with increased adiposity, oxidative stress, and reduced glucose tolerance, independent of obesity. We propose that mild uncoupling may be induced secondary to age-associated oxidative stress as a mechanism to dissipate the proton-motive force and protect against further reactive oxygen species production and damage.

Insulin resistance and lipid accumulation occur with aging, perhaps due to mitochondrial dysfunction. In this issue of Cell Metabolism (Lee et al., 2010), older mice overexpressing mitochondrial targeted catalase had reduced muscle mitochondrial oxidative damage, lower intramuscular lipid, and improved insulin sensitivity, suggesting that enhanced ROS scavenging prevents age-associated mitochondrial impairments and insulin resistance., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Introduction: There is a need to develop accurate devices for measuring daily energy expenditure under free-living conditions, particularly given our current obesity epidemic., Purpose: The purpose of the present study was to evaluate the validity of energy expenditure estimates from two portable armband devices, the SenseWear Pro3 Armband (SWA) monitor and the SenseWear Mini Armband (Mini) monitor, under free-living conditions., Methods: Participants in the study (30 healthy adults aged 24-60 yr) wore both monitors for 14 consecutive days, including while sleeping. Criterion values for total energy expenditure (TEE) were determined using doubly labeled water (DLW), the established criterion standard method for free-living energy expenditure assessment., Results: The average TEE estimates were within 112 kcal·d−¹ for the SWA and within 22 kcal·d−¹ for the Mini, but the absolute error rates (computed as the average absolute value of the individual errors) were similar for the two monitors (SWA = 8.1% ± 6.8%, Mini = 8.3% ± 6.5%). Using intraclass correlation (ICC) analysis, significant agreements were found between the SWA and DLW estimates of energy expenditure (ICC = 0.80, 95% CI = 0.89-0.70) and between the Mini and DLW (ICC = 0.85, 95% CI = 0.92-0.76). Graphical plots of the DLW TEE values against the difference between DLW and monitor estimates of TEE showed that the agreement was consistent across a range of TEE values., Conclusions: The SenseWear Pro3 and the SenseWear Mini armbands show promise for accurately measuring daily energy expenditure under free-living conditions. However, more work is needed to improve the ability of these monitors to accurately measure energy expenditure at higher levels of expenditure.

The fastest growing segment of the US population, and that of other developed countries, is the oldest-old (aged >85 years). Many children born after the year 2000 in countries with the longest lived residents may live to see their 100th birthday. The combination of reduced mortality along with reduced fertility in developed countries is producing 'population aging', and the comorbidities associated with aging are becoming important public health issues. Age-associated obesity is one such important public health issue. Aging is associated with significant changes in body composition, including loss of skeletal muscle mass and increased visceral fat accumulation. The loss of muscle mass is accompanied by a disproportionate decline in muscle strength (up to three-times greater than the loss of mass), indicative of reduced muscle 'quality' or muscle dysfunctionality. Aging is characterized by markedly reduced physical activity and a drop in resting metabolic rate that is disproportionate to the loss of muscle mass, with a shift towards preferentially oxidizing carbohydrate at the expense of fat. A combination of these factors may act to increase muscular lipid infiltration and decrease insulin sensitivity; however, the cause and effect relationship remains undetermined. Changes in cellular energy (i.e., ATP) requirement owing to decreased ion channel activity, decreased protein synthesis or increased mitochondrial energy efficiency may underlie the decreased resting metabolic rate. Increasing energy demand through physical activity may alleviate some of the adverse metabolic changes that are associated with aging.

Mitochondria play a key role in energy metabolism in many tissues, including skeletal muscle and liver. Inherent disorders of mitochondria such as DNA deletions cause major disruption of metabolism and can result in severe impairment or death. However, the occurrence of such disorders is extremely rare and cannot account for the majority of metabolic disease. Recently, mitochondrial dysfunction of a more subtle nature in skeletal muscle has been implicated in the pathology of chronic metabolic disease characterized by insulin resistance such as obesity, type 2 diabetes mellitus, and aging. This hypothesis has been substantiated by work from Shulman and colleagues, showing that reduced mitochondrial oxidative capacity underlies the accumulation of intramuscular fat causing insulin resistance with aging. However, recent work by Nair and coworkers has demonstrated that mitochondrial activity may actually be higher in persons exposed to high-calorie diet leading to obesity, suggesting that the accumulation of intramuscular fat and associated fatty acid metabolites may be directly responsible for the development of insulin resistance, independent of mitochondrial function. These inconsistent findings have promoted ongoing investigation into mitochondrial function to determine whether impaired function is a cause or consequence of metabolic disorders.

Purpose of Review: To discuss the potential importance of spontaneous physical activity in regulating body weight and outline possible reasons for the large interindividual variance in spontaneous physical activity., Recent Findings: Spontaneous physical activity is highly variable among people, with some having high levels and some low, and can contribute significantly to interindividual differences in total daily energy expenditure. Cross-sectionally, spontaneous physical activity is inversely related to body weight; however, more importantly, spontaneous physical activity is inversely associated with weight gain in prospective studies, and experimental weight perturbations do not appear to change spontaneous physical activity behavior. Spontaneous physical activity is a familial trait and is biologically influenced, although the environment exerts a significant impact., Summary: Although spontaneous physical activity is a biologically driven behavior, interventions to increase nonexercise activity within the workplace and school hold promise in increasing daily energy expenditure for the average sedentary American. However, many large-scale efforts will need to take place within our sedentary-promoting environment to encourage more daily spontaneous physical activity-related activity.

Physical activity (PA) is known to decline with age; however, there is a paucity of data on activity in persons who are in their nineties and beyond. We used objective and reliable methods to measure PA in nonagenarians (>or=90 yr; n=98) and hypothesized that activity would be similar to that of aged (60-74 yr; n=58) subjects but less than in young (20-34 yr; n=53) volunteers. Total energy expenditure (TEE) was measured by doubly labeled water over 14 days and resting metabolic rate (RMR) by indirect calorimetry. Measures of PA included activity energy expenditure adjusted for body composition, TEE adjusted for RMR, physical activity level (PAL), and activity over 14 days by accelerometry expressed as average daily durations of light and moderate activity. RMR and TEE were lower with increasing age group (P<0.01); however, RMR was not different between aged and nonagenarian subjects after adjusting for fat-free mass, fat mass, and sex. Nonagenarians had a lower PAL and were more sedentary than the aged and young groups (P<0.01); however, the nonagenarians who were more active on a daily basis walked further during a timed test, indicating higher physical functionality. For all measures of activity, no differences were found between young and aged volunteers. PA was markedly lower in nonagenarians compared with young and aged adults. Interestingly, PA was similar between young volunteers and those who were in their 60s and 70s, likely due to the sedentary nature of our society, particularly in young adults.

Objective: A low resting metabolic rate (RMR) is considered a risk factor for weight gain and obesity; however, due to the greater fat-free mass (FFM) found in obesity, detecting an impairment in RMR is difficult. The purposes of this study were to determine the RMR in lean and obese women controlling for FFM and investigate activity energy expenditure (AEE) and daily activity patterns in the two groups., Methods and Procedures: Twenty healthy, non-smoking, pre-menopausal women (10 lean and 10 obese) participated in this 14-day observational study on free-living energy balance. RMR was measured by indirect calorimetry; AEE and total energy expenditure (TEE) were calculated using doubly labeled water (DLW), and activity patterns were investigated using monitors. Body composition including FFM and fat mass (FM) was measured by dual energy X-ray absorptiometry (DXA)., Results: RMR was similar in the obese vs. lean women (1601 +/- 109 vs. 1505 +/- 109 kcal/day, respectively, P = 0.12, adjusting for FFM and FM). Obese women sat 2.5 h more each day (12.7 +/- 3.2 h vs. 10.1 +/- 2.0 h, P < 0.05), stood 2 h less (2.7 +/- 1.0 h vs. 4.7 +/- 2.2 h, P = 0.02) and spent half as much time in activity than lean women (2.6 +/- 1.5 h vs. 5.4 +/- 1.9 h, P = 0.002)., Discussion: RMR was not lower in the obese women; however, they were more sedentary and expended less energy in activity than the lean women. If the obese women adopted the activity patterns of the lean women, including a modification of posture allocation, an additional 300 kcal could be expended every day.

Current physical activity recommendations call for 30 minutes of moderate-intensity activity on most days of the week, or the equivalent of expending approximately 1000 kcal in activity per week. These recommendations were formulated based on reducing the risk for chronic disease, but they do not appear adequate for weight loss and maintenance. Data from epidemiologic studies and randomized trials indicate that closer to 60 to 90 minutes of moderate-intensity activity every day is required for maintaining a reduced body weight, equivalent to expending 2500 to 2800 kcal in activity per week. Relevant studies leading to this conclusion are reviewed in this manuscript. However, to make a dent in the prevalence of obesity by targeting physical activity and food intake, it is imperative to address the current "built" environment, which is conducive to a sedentary lifestyle and overconsumption of energy. Only then will rigorous activity recommendations be easier to implement.

Background: Accurately determining rates of energy expenditure (EE) under free-living conditions is important in understanding the mechanisms involved in the development and prevention of obesity. Metabolic carts are not portable enough for most free-living situations. The purpose of this study was to compare a portable, handheld indirect calorimetry device (HealtheTech Incorporated, Golden, CO) to a metabolic cart (Physio-Dyne Instrument Corporation, Quogue, NY) during 3 different physiologic states., Methods: EE was measured by both the handheld calorimeter (5-10 minutes) and the metabolic cart (15-20 minutes) in 20 healthy subjects (18-35 years of age). Measurements were made during 3 physiologic states: (1) postabsorptive rest (REE), (2) postprandial rest (fed energy expenditure, FEE), and (3) while walking in place (activity energy expenditure, AEE)., Results: There were no significant differences between the means of the cart vs the hand-held device for REE (mean +/- SE; kcal/d; 1552 +/- 64 vs 1551 +/- 63), FEE (1875 +/- 99 vs 1825 +/- 86), and AEE (3333 +/- 218 vs 3489 +/- 152). The range over which the techniques were tested was 1300-5000 kcal/d. The agreement between the 2 methods was excellent for REE (0.80, p < .0001), FEE (0.89, p < .0001), and AEE (0.75, p < .0002)., Conclusions: Compared with the metabolic cart, the handheld device provided similar estimates of energy expenditure during resting, postprandial, and physically active states. This suggests that portable indirect calorimetry devices can provide reliable and valuable information in free-living research situations for which maximal energy expenditure is <5000 kcal/d.

Objective: To investigate the effects of mothers' and fathers' eating behaviors, child feeding practices, and BMI on percentage body fat and BMI in their children., Research Methods and Procedures: Four hundred fifty-eight parents (239 mothers, 219 fathers) were asked to complete two questionnaires: the Three-Factor Eating Questionnaire and the Child Feeding Questionnaire, which measure dimensions of parent eating behavior and child feeding practices, respectively. Parent BMI was calculated from self-reported height and weight; children's measures included BMI and percentage fat assessed by DXA. Regression analyses were used to analyze relationships between parents' BMI and questionnaire scores and children's weight status., Results: One hundred forty-three mothers and 68 fathers returned questionnaires, representing parents of 148 children 3 to 5 years old (78 boys). Children's weight was related to mothers' BMI, but not fathers'. Girls had a greater BMI if either parent reported being overweight as a child, and both girls and boys were likely to be overweight if their mothers believed they had risky eating habits (fussiness, eating too much, etc.). Girls with fathers who were more controlling had a higher percentage fat; these fathers were also more concerned about their daughters' future health., Discussion: Mothers exert a strong influence over their children's weight and seem to be more concerned about their children's eating behaviors; however, fathers play a role in imposing child feeding practices. Gender bias may be present in child feeding, as suggested by dissimilar effects of parent practices on the weight status of girls vs. boys. Fathers should be included in future studies analyzing parent feeding practices and children's weight outcome.