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Biomedical subjects

James A Levine

Publications and source records attributed to James A Levine.

At least 19 recordsLinked to original sources

Galectin-3 stimulates preadipocyte proliferation and is up-regulated in growing adipose tissue.

OBJECTIVE: Some cytokines and mediators of inflammation can alter adiposity through their effects on adipocyte number. To probe the molecular basis of obesity, this study determined whether galectin-3 was present in adipose tissue and investigated its effects on fat cell number. RESEARCH METHODS AND PROCEDURES: In the first study, obesity-prone C57BL/6J mice were fed with high-fat (58%) diet. Epididymal fat pads were collected at Day 0, Day 60, and Day 120 after the start of high-fat feeding. RESULTS: Levels of adipocyte galectin-3 protein, determined using Western blot analysis, increased as the mice became obese. Galectin-3 mRNA and protein were then detected in human adipose tissue, primarily in the preadipocyte fraction. It was found that recombinant human galectin-3 stimulated proliferation of primary cultured preadipocytes as well as DNA synthesis through lectin-carbohydrate interaction. DISCUSSION: Galectin-3, which has been known to play a versatile role especially in immune cells, might play a role also in adipose tissue and be associated with the pathophysiology of obesity.

Adipocytes↗

Impact of endurance training on murine spontaneous activity, muscle mitochondrial DNA abundance, gene transcripts, and function.

We hypothesized that enhanced skeletal muscle mitochondrial function following aerobic exercise training is related to an increase in mitochondrial transcription factors, DNA abundance [mitochondrial DNA (mtDNA)], and mitochondria-related gene transcript levels, as well as spontaneous physical activity (SPA) levels. We report the effects of daily treadmill training on 12-wk-old FVB mice for 5 days/wk over 8 wk at 80% peak O(2) consumption and studied the training effect on changes in body composition, glucose tolerance, muscle mtDNA muscle, mitochondria-related gene transcripts, in vitro muscle mitochondrial ATP production capacity (MATPC), and SPA levels. Compared with the untrained mice, the trained mice had higher peak O(2) consumption (+18%; P < 0.001), lower percentage of abdominal (-25.4%; P < 0.02) and body fat (-19.5%; P < 0.01), improved glucose tolerance (P < 0.04), and higher muscle mitochondrial enzyme activity (+19.5-43.8%; P < 0.04) and MATPC (+28.9 to +32.4%; P < 0.01). Gene array analysis showed significant differences in mRNAs of mitochondria-related ontology groups between the trained and untrained mice. Training also increased muscle mtDNA (+88.4 to +110%; P < 0.05), peroxisome proliferative-activated receptor-gamma coactivator-1alpha protein (+99.5%; P < 0.04), and mitochondrial transcription factor A mRNA levels (+21.7%; P < 0.004) levels. SPA levels were higher in trained mice (P = 0.056, two-sided t-test) and significantly correlated with two separate substrate-based measurements of MATPC (P < 0.02). In conclusion, aerobic exercise training enhances muscle mitochondrial transcription factors, mtDNA abundance, mitochondria-related gene transcript levels, and mitochondrial function, and this enhancement in mitochondrial function occurs in association with increased SPA.

Animals↗

Facial skin surface temperature changes during a "concealed information" test.

When individuals who commit a crime are questioned, they often show involuntary physiological responses to remembered details of that crime. This phenomenon is the basis for the concealed information test, in which rarely occurring crime-related details are embedded in a series of more frequently occurring crime-irrelevant items while respiratory, cardiovascular, and electrodermal responses are recorded. Two experiments were completed to investigate the feasibility of using facial skin surface temperature (SST) measures recorded using high definition thermographic images as the physiological measure during a concealed information test. Participants were randomly assigned to nondeceptive or deceptive groups. Deceptive participants completed a mock-crime paradigm. A focal plane array thermal imaging radiometer was used to monitor SST while crime-relevant and crime-irrelevant items were verbally presented to each participant. During both experiments, there were significant facial SST differences between deceptive and nondeceptive participants early in the analysis interval. In the second experiment, hemifacial (i.e., "half-face" divided along the longitudinal axis) effects were combined with the bilateral responses to correctly classify 91.7% of participants. These results suggest that thermal image analysis can be effective in discriminating deceptive and nondeceptive individuals during a concealed information test.

Adult↗

Non-exercise activity thermogenesis: the crouching tiger hidden dragon of societal weight gain.

Non-exercise activity thermogenesis (NEAT) is the energy expenditure of all physical activities other than volitional sporting-like exercise. NEAT includes all the activities that render us vibrant, unique, and independent beings such as working, playing, and dancing. Because people of the same weight have markedly variable activity levels, it is not surprising that NEAT varies substantially between people by up to 2000 kcal per day. Evidence suggests that low NEAT may occur in obesity but in a very specific fashion. Obese individuals appear to exhibit an innate tendency to be seated for 2.5 hours per day more than sedentary lean counterparts. If obese individuals were to adopt the lean "NEAT-o-type," they could potentially expend an additional 350 kcal per day. Obesity was rare a century ago and the human genotype has not changed over that time. Thus, the obesity epidemic may reflect the emergence of a chair-enticing environment to which those with an innate tendency to sit, did so, and became obese. To reverse obesity, we need to develop individual strategies to promote standing and ambulating time by 2.5 hours per day and also re-engineer our work, school, and home environments to render active living the option of choice.

Animals↗

Weekly changes in basal metabolic rate with eight weeks of overfeeding.

OBJECTIVE: The contribution of basal metabolic rate (BMR) to weight gain susceptibility has long been debated. We wanted to examine whether BMR changes in a linear fashion with overfeeding. Our hypothesis was that BMR does not increase linearly with 1000-kcal/d overfeeding in lean healthy subjects over 8 weeks. The null hypothesis states that BMR increases linearly with 1000-kcal/d overfeeding in lean healthy subjects. RESEARCH METHODS AND PROCEDURES: Initially, 16 lean healthy sedentary subjects completed 2 weeks of weight maintenance feeding at the General Clinical Research Center. The subjects were then overfed by 1000 kcal/d over 8 weeks. BMR was measured under standard conditions each week using indirect calorimetry. RESULTS: Baseline BMR was 1693 +/- 154.5 kcal/d. BMR increased from 1711 +/- 201.3 kcal/d at week 1 of overfeeding to 1781 +/- 171.65 kcal/d at the second week of overfeeding (p = 0.05). BMR fell during the third week of overfeeding to 1729 +/- 179.5 kcal/d (p = 0.05). After 5 weeks of overfeeding, BMR reached a plateau. Thereafter, there was no further change. Comparison of BMR with weeks of overfeeding was significantly different compared with the linear model (p < 0.05). DISCUSSION: Increases in BMR in lean sedentary healthy subjects with 1000-kcal/d overfeeding are not linear over 8 weeks. There seems to be a short-term increase in BMR in the first 2 weeks of overfeeding that is not representative of longer-term changes.

Adiposity↗

Energy expenditure of sedentary screen time compared with active screen time for children.

OBJECTIVE: We examined the effect of activity-enhancing screen devices on children's energy expenditure compared with performing the same activities while seated. Our hypothesis was that energy expenditure would be significantly greater when children played activity-promoting video games, compared with sedentary video games. METHODS: Energy expenditure was measured for 25 children aged 8 to 12 years, 15 of whom were lean, while they were watching television seated, playing a traditional video game seated, watching television while walking on a treadmill at 1.5 miles per hour, and playing activity-promoting video games. RESULTS: Watching television and playing video games while seated increased energy expenditure by 20 +/- 13% and 22 +/- 12% above resting values, respectively. When subjects were walking on the treadmill and watching television, energy expenditure increased by 138 +/- 40% over resting values. For the activity-promoting video games, energy expenditure increased by 108 +/- 40% with the EyeToy (Sony Computer Entertainment) and by 172 +/- 68% with Dance Dance Revolution Ultramix 2 (Konami Digital Entertainment). CONCLUSIONS: Energy expenditure more than doubles when sedentary screen time is converted to active screen time. Such interventions might be considered for obesity prevention and treatment.

Child↗

Central orexin sensitivity, physical activity, and obesity in diet-induced obese and diet-resistant rats.

Nonexercise activity thermogenesis (NEAT), the most variable component of energy expenditure, can account for differential capacities for human weight gain. Also highly variable, spontaneous physical activity (SPA) may similarly affect weight balance in animals. In the following study, we utilized the rat model of obesity, the diet-induced obese (DIO) rat, as well as the diet-resistant (DR) rat strain, to investigate how access to a high-fat diet alters SPA and the associated energy expenditure (i.e., NEAT). DIO and DR rats showed no differences in the amount of SPA before access to the high-fat diet. After 29 days on a high-fat diet, the DIO rats showed significant decreases in SPA, whereas the DR rats did not. Next, we wanted to determine whether the DIO and DR rats showed differential sensitivity to microinjections of orexin into the paraventricular nucleus of the hypothalamus (PVN). Unilateral guide cannulae were implanted, aimed at the PVN. Orexin A (0, 0.125, 0.25, and 1.0 nmol in 500 nl) was microinjected through the guide cannula into the PVN, then SPA and energy expenditure were measured for 2 h. Using the response to vehicle as a baseline, the DR rats showed significantly greater increase in NEAT compared with the DIO rats. These data indicate that diet-induced obesity is associated with decreases in SPA and a lack of increase in NEAT. A putative mechanism for changes in NEAT that accompany obesity is a decreased sensitivity to the NEAT-activating effects of neuropeptides such as orexin.

Animals↗

Caloric restriction and physical activity in zebrafish (Danio rerio).

Understanding the mechanism of energy flux may be critical for explaining how obesity has emerged as a public health epidemic. It is known that changes in caloric intake predictably alter physical activity levels (PA) in mammals. Here, our goal was to test the hypothesis that fasting induces a biphasic pattern of change in PA by measuring PA before and after long-term food deprivation in zebrafish. Compared to control-fed fish, food-deprived fish showed a significant increase in PA levels during the first 2 days of food deprivation. Subsequently, however, fasted fish showed a significant chronic decrease in PA compared to fish fed at weight-maintenance levels. These data are comparable to those seen with mammals, which also show a biphasic response of PA to caloric restriction. In a separate group of fish, long-term food deprivation, associated with decreases in PA, induced a significant increase in brain preproorexin mRNA levels compared to fed controls. No change in orexin mRNA was seen after 2 days of food deprivation. The finding that orexin mRNA expression is altered only after long-term starvation suggests that orexin may be coupled with the changes in PA seen at this time. Thus, the association between negative energy balance and reductions in PA occurs across genera in biology and is associated with predictable neurological changes in brain gene expression.

Animals↗

Interindividual variation in posture allocation: possible role in human obesity.

Obesity occurs when energy intake exceeds energy expenditure. Humans expend energy through purposeful exercise and through changes in posture and movement that are associated with the routines of daily life [called nonexercise activity thermogenesis (NEAT)]. To examine NEAT's role in obesity, we recruited 10 lean and 10 mildly obese sedentary volunteers and measured their body postures and movements every half-second for 10 days. Obese individuals were seated, on average, 2 hours longer per day than lean individuals. Posture allocation did not change when the obese individuals lost weight or when lean individuals gained weight, suggesting that it is biologically determined. If obese individuals adopted the NEAT-enhanced behaviors of their lean counterparts, they might expend an additional 350 calories (kcal) per day.

Activities of Daily Living↗

Measurement of energy expenditure.

Measurement of energy expenditure in humans is required to assess metabolic needs, fuel utilisation, and the relative thermic effect of different food, drink, drug and emotional components. Indirect and direct calorimetric and non-calorimetric methods for measuring energy expenditure are reviewed, and their relative value for measurement in the laboratory and field settings is assessed. Where high accuracy is required and sufficient resources are available, an open-circuit indirect calorimeter can be used. Open-circuit indirect calorimeters can employ a mask, hood, canopy or room/chamber for collection of expired air. For short-term measurements, mask, hood or canopy systems suffice. Chamber-based systems are more accurate for the long-term measurement of specified activity patterns but behaviour constraints mean they do not reflect real life. Where resources are limited and/or optimum precision can be sacrificed, flexible total collection systems and non-calorimetric methods are potentially useful if the limitations of these methods are appreciated. The use of the stable isotope technique, doubly labelled water, enables total daily energy expenditure to be measured accurately in free-living subjects. The factorial method for combining activity logs and data on the energy costs of activities can also provide detailed information on free-living subjects.

Basal Metabolism↗

Laboratory measurement of posture allocation and physical activity in children.

PURPOSE: The purpose of this study was to validate the combined use of inclinometers and accelerometers to measure body posture and movement in children in a laboratory setting. METHODS: We performed two separate experiments. In the first experiment, we tested the hypothesis that four inclinometers (tilt sensors) could be used to capture body posture in children. We observed and recorded body posture in eight healthy children (mean +/- SD; body mass index (BMI), 18 +/- 3 kg x m(-2)) on 2880 occasions and compared these records with the inclinometer data. In the second experiment, the hypothesis was that two inclinometers could be used to determine whether 18 children (BMI, 21 +/- 5 kg x m(-2)) were sedentary. We observed and recorded sedentariness (sitting/lying compared to standing) on 5575 occasions and compared these records with the inclinometer data. In both of these experiments, we also addressed the hypothesis that accelerometer output, when measured at varying velocities, correlated with walking energy expenditure. RESULTS: In experiment 1, body posture was correctly identified in 2880 out of 2880 inclinometer measurements. In experiment 2, sedentary behavior was correctly identified in 5575 out of 5575 occasions. For the entire group, acceleration and body weight correlated well with energy expenditure (r2 = 0.84). CONCLUSION: The inclinometer-accelerometer system that we tested can be used to measure body posture and movement. We can measure sedentary behavior using two inclinometers instead of four inclinometers. This monitoring system may be useful for measuring energy expenditure, body posture, and physical activity in children.

Calorimetry, Indirect↗

Role of nonexercise activity thermogenesis (NEAT) in obesity.

Obesity develops when there is an imbalance between energy intake and energy expenditure, which can vary daily within and among individuals. High levels of energy intake and low levels of energy expenditure contribute to obesity, both together and independently. Energy expenditure from exercise associated with formal programs is encouraged for health and weight loss, but most individuals get very little formal exercise. Nonexercise activity thermogenesis (NEAT) is the cumulative energy expended through all other activities of daily living. It is highly variable among individuals; it is controlled by the environment and, possibly, neurobiologically. Mounting evidence suggests that NEAT is critical in determining a person's susceptibility to body fat deposition and is a major factor in human obesity. Recent research supported by the Minnesota Partnership for Biotechnology and Medical Genomics, a state-sponsored collaborative effort of the University of Minnesota and Mayo Clinic, is helping to define the complex brain regulation of NEAT and its role in obesity. This article reviews the evidence for NEAT and the impact of NEAT on obesity.

Activities of Daily Living↗

Commercially available pedometers: considerations for accurate step counting.

BACKGROUND: Many commercially available pedometers undercount, especially at slower speeds. We examined the effects of age, obesity, and self-selected walking speed on pedometer accuracy. We also compared the accuracy of piezoelectric and spring-levered pedometers at slow walking speeds. METHODS: Study 1: 259 subjects walked on a motorized treadmill at two self-selected walking speeds. Steps were counted using a spring-levered pedometer. Study 2: 32 subjects walked on a motorized treadmill at slow walking (1.0-2.6 MPH) speeds. Steps were counted using spring-levered and piezoelectric pedometers. RESULTS: Study 1: self-selected walking speed and pedometer accuracy decreased with increasing age, weight, and body mass index (BMI). Accuracy was 71% below 2.0 MPH, 74-91% between 2.0 and 3.0 MPH, and 96% above 3.0 MPH. Decreased accuracy was best predicted by increasing age. Study 2: between 1.8 and 2.0 MPH, the accuracy of the piezoelectric pedometer (>97%) exceeded that of the spring-levered pedometers (52-95%). Even at 1.0 MPH, accuracy of the piezoelectric pedometer (56.4 +/- 33.8%) was superior to the spring-levered pedometers (7-20%). CONCLUSION: Accuracy of all pedometers tested exceeded 96% at speeds 3.0 MPH, but decreased at slower walking speeds. In individuals that naturally ambulate at slower walking speeds (e.g., elderly), we recommend the use of more sensitive (e.g., piezoelectric) pedometers.

Adult↗

Variability in energy expenditure and its components.

PURPOSE OF REVIEW: To review factors contributing to variation in total daily energy expenditure and its primary components: (1) resting metabolic rate; (2) diet-induced thermogenesis; and (3) activity thermogenesis, including exercise energy expenditure and nonexercise activity. For each component, the expected magnitude of intra-individual variability is also considered. We also reviewed studies that quantified the variability in 24 h energy expenditure. RECENT FINDINGS: In humans, the coefficient of variation in the components of total daily energy expenditure is around 5-8% for resting metabolic rate, 1-2% for exercise energy expenditure, and around 20% for diet-induced thermogenesis. The coefficient of variance for 24 h energy expenditure measured using a room calorimeter for resting metabolic rate is around 5-10%. Thus, these measures are all rather reproducible. Total daily energy expenditure varies several-fold in humans, not due to variation in resting metabolic rate, diet-induced thermogenesis, or exercise thermogenesis, but rather, due to variations in nonexercise activity. A variety of factors impact nonexercise activity, including occupation, environment, education, genetics, age, gender, and body composition, but little is known about the magnitude of effect. SUMMARY: Resting metabolic rate, diet-induced thermogenesis, exercise energy expenditure, and 24 h energy expenditure are highly reproducible. Coefficient of variation is smallest for exercise energy expenditure, followed by resting metabolic rate, 24 h energy expenditure, and diet-induced thermogenesis. There is considerable variability in total daily energy expenditure, largely due to variations in nonexercise activity. Although the factors that impact upon nonexercise activity are understood, their contribution to variation in total daily energy expenditure is unclear.

Basal Metabolism↗

Body composition profiles derived from dual-energy X-ray absorptiometry, total body scan, and mortality.

Little has been reported on the association of derived body composition data and cardiovascular mortality. The authors defined body composition profiles based on one- and two-variable measures from dual-energy x-ray absorptiometry (DXA) total body scans. Scan results are labeled "apple" if Z score for percent of total fat in trunk is >0 and "pear" if Z score for height-corrected limb fat is > or = 0. The fat measures were combined to define four body composition profiles: "pickle," "avocado," "mango," and "barrel." A third axis, the Z score of height-corrected limb lean tissue, is an index of skeletal muscle mass and was used to label subjects as "hard" or "soft." Subjects (n=324) who were in good health from Malmö, Sweden, underwent body composition analysis using DXA and were followed for 10 years. The distribution of body composition profiles was similar for both genders and across age groups. Among subjects aged 50-74 years at baseline (n=116), there were 21 deaths. Barrel had the highest mortality rate: 13/39 (33.3%) mortality for barrels, compared with 8/77 (10.4%) mortality for non-barrels; mortality odds ratio, 3.2; 95% confidence interval, 1.45-7.08. The increased mortality was principally attributable to cardiovascular cause-related deaths. Soft (sarcopenia) was also associated with increased mortality (25.9%; p=0.05), but not cardiovascular cause-related deaths, whereas the total mortality among apples was not significantly increased but cardiovascular cause-related deaths were predominant (75%; p=0.02). The authors propose that DXA-body composition profiles can identify increased mortality risk of magnitude similar to major cardiovascular risk factors and may prove useful in health assessment.

Absorptiometry, Photon↗

Non-exercise activity thermogenesis (NEAT).

Non-exercise activity thermogenesis (NEAT) is the energy expended for everything we do that is not sleeping, eating or sports-like exercise. NEAT can be measured by one of two approaches. The first approach is to measure or estimate total NEAT. Here, total daily energy expenditure is measured and from it, the basal metabolic rate-plus-thermic effect of food is subtracted. The second approach is the factoral approach whereby the components of NEAT are quantified and total NEAT calculated by summing these components. The amount of NEAT that humans perform represents the product of the amount and types of physical activities and the thermogenic cost of each activity. The factors that impact a human's NEAT are readily divisible in biological factors such as weight, gender and body composition and environmental factors such occupation or dwelling within a "concrete jungle." The impact of these factors combined explains the substantial variance in human NEAT. The variability in NEAT might be viewed as random and unprogrammed but human data contradict this thesis. It appears that changes in NEAT accompany experimentally induced changes in energy balance and may be important in the physiology of weight change. NEAT and a sedentary lifestyle may thus be of profound importance in obesity.

Age Factors↗

Nonexercise activity thermogenesis (NEAT): environment and biology.

Nonexercise activity thermogenesis (NEAT) is the energy expended for everything that is not sleeping, eating, or sports-like exercise. It includes the energy expended walking to work, typing, performing yard work, undertaking agricultural tasks, and fidgeting. NEAT can be measured by one of two approaches. The first is to measure or estimate total NEAT. Here, total daily energy expenditure is measured, and from it "basal metabolic rate-plus-thermic effect of food" is subtracted. The second is the factoral approach, whereby the components of NEAT are quantified, and total NEAT is calculated by summing these components. The amount of NEAT that humans perform represents the product of the amount and types of physical activities and the thermogenic cost of each activity. The factors that impact a human's NEAT are readily divisible into environmental factors, such as occupation or dwelling within a "concrete jungle," and biological factors such as weight, gender, and body composition. The combined impact of these factors explains the substantial variance in human NEAT. The variability in NEAT might be viewed as random, but human and animal data contradict this. It appears that changes in NEAT subtly accompany experimentally induced changes in energy balance and are important in the physiology of weight change. Inadequate modulation of NEAT plus a sedentary lifestyle may thus be important in obesity. It then becomes intriguing to dissect mechanistic studies that delineate how NEAT is regulated into neural, peripheral, and humoral factors. A scheme is described in this review in which NEAT corresponds to a carefully regulated "tank" of physical activity that is crucial for weight control.

Adaptation, Physiological↗

Orexin A (hypocretin 1) injected into hypothalamic paraventricular nucleus and spontaneous physical activity in rats.

In humans, nonexercise activity thermogenesis (NEAT) increases with positive energy balance. The mediator of the interaction between positive energy balance and physical activity is unknown. In this study, we address the hypothesis that orexin A acts in the hypothalamic paraventricular nucleus (PVN) to increase nonfeeding-associated physical activity. PVN-cannulated rats were injected with either orexin A or vehicle during the light and dark cycle. Spontaneous physical activity (SPA) was measured using arrays of infrared activity sensors and night vision videotaped recording (VTR). O(2) consumption and CO(2) production were measured by indirect calorimetry. Feeding behavior was assessed by VTR. Regardless of the time point of injection, orexin A (1 nmol) was associated with dramatic increases in SPA for 2 h after injection (orexin A: 6.27 +/- 1.95 x 10(3) beam break count, n = 24; vehicle: 1.85 +/- 1.13 x 10(3), n = 38). This increase in SPA was accompanied by compatible increase in O(2) consumption. Duration of feeding was increased only when orexin A was injected in the early light phase and accounted for only 3.5 +/- 2.5% of the increased physical activity. In a dose-response experiment, increases in SPA were correlated with dose of orexin A linearly up to 2 nmol. PVN injections of orexin receptor antagonist SB-334867 were associated with decreases in SPA and attenuated the effects of PVN-injected orexin A. Thus orexin A can act in PVN to increase nonfeeding-associated physical activity, suggesting that this neuropeptide might be a mediator of NEAT.

Animals↗