Brain orexin promotes obesity resistance

Resistance to obesity is becoming an exception rather than the norm, and understanding mechanisms that lead some to remain lean in spite of an obesigenic environment is critical if we are to find new ways to reverse this trend. Levels of energy intake and physical activity both contribute to body weight management, but it is challenging for most to adopt major long-term changes in either factor. Physical activity outside of formal exercise, also referred to as activity of daily living, and in stricter form, spontaneous physical activity (SPA), may be an attractive modifiable variable for obesity prevention. In this review, we discuss individual variability in SPA and NEAT (nonexercise thermogenesis, or the energy expended by SPA) and its relationship to obesity resistance. The hypothalamic neuropeptide orexin (hypocretin) may play a key role in regulating SPA and NEAT. We discuss how elevated orexin signaling capacity, in the context of a brain network modulating SPA, may play a major role in defining individual variability in SPA and NEAT. Greater activation of this SPA network leads to a lower propensity for fat mass gain and therefore may be an attractive target for obesity prevention and therapy.     

Measurement of the components of nonexercise activity thermogenesis

Nonexercise activity thermogenesis (NEAT) accounts for the vast majority of nonresting metabolic rate and changes in NEAT-predicted susceptibility to fat gain with overfeeding. Measuring physical activity and its components in free-living humans has been a long-standing challenge. In this study, we combine information about lightweight sensors that capture data on body position and motion with laboratory measures of energy expenditure to calculate nonfidgeting NEAT. This measurement of nonfidgeting NEAT was compared with total NEAT measured in a room calorimeter in 11 healthy subjects. The measurement of nonfidgeting NEAT accounted for 85 +/- 9% of total NEAT measured in the room calorimeter. The intraclass correlation coefficient for the two methods was 0.86 (95% confidence interval 0.56, 0.96; P < 0.05). This suggests that 86% of the variance is attributable to between-subject variance and 14% to between-method disagreement. These instruments are applicable to free-living subjects; they are stand-alone, are lightweight, and allow normal daily activities. This novel technology has potential application for not only assessing NEAT but also tracking physical activity in free-living humans.     

Neuroregulation of nonexercise activity thermogenesis and obesity resistance

High levels of spontaneous physical activity in lean people and the nonexercise activity thermogenesis (NEAT) derived from that activity appear to protect lean people from obesity during caloric challenge, while obesity in humans is characterized by dramatically reduced spontaneous physical activity. We have similarly demonstrated that obesity-resistant rats have significantly greater spontaneous physical activity than obesity-prone rats, and that spontaneous physical activity predicts body weight gain. Although the energetic cost of activity varies between types of activity and may be regulated, individual level of spontaneous physical activity is important in determining propensity for obesity. We review the current status of knowledge about the brain mechanisms involved in controlling the level of spontaneous physical activity and the NEAT so generated. Focus is on potential neural mediators of spontaneous physical activity and NEAT, including orexin A (also known as hypocretin 1), agouti-related protein, ghrelin, and neuromedin U, in addition to brief mention of neuropeptide Y, corticotrophin releasing hormone, cholecystokinin, estrogen, leptin, and dopamine effects on spontaneous physical activity. We further review evidence that strain differences in orexin stimulation pathways for spontaneous physical activity and NEAT appear to track with the body weight phenotype, thus providing a potential mechanistic explanation for reduced activity and weight gain.     

Effects of experimental weight perturbation on skeletal muscle work efficiency in human subjects

Maintenance of reduced or elevated body weight results in respective decreases or increases in energy expended in physical activity, defined as 24-h energy expenditure excluding resting energy expenditure and the thermic effect of feeding, beyond those attributable to weight change. We examined skeletal muscle work efficiency by graded cycle ergometry and, in some subjects, rates of gastrocnemius muscle ATP flux during exercise by magnetic resonance spectroscopy (MRS), in 30 subjects (15 males, 15 females) at initial weight and 10% below initial weight and in 8 subjects (7 males, 1 female) at initial weight and 10% above initial weight to determine whether changes in skeletal muscle work efficiency at altered body weight were correlated with changes in the energy expended in physical activity. At reduced weight, muscle work efficiency was increased in both cycle ergometry [mean (SD) change = +26.5 (26.7)%, P < 0.001] and MRS [ATP flux change = -15.2 (23.2)%, P = 0.044] studies. Weight gain resulted in decreased muscle work efficiency by ergometry [mean (SD) change = -17.8 (20.5)%, P = 0.043]. Changes in muscle efficiency at altered body weight accounted for 35% of the change in daily energy expended in physical activity.     

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.     

Spontaneous activity, economy of activity, and resistance to diet-induced obesity in rats bred for high intrinsic aerobic capacity

Though obesity is common, some people remain resistant to weight gain even in an obesogenic environment. The propensity to remain lean may be partly associated with high endurance capacity along with high spontaneous physical activity and the energy expenditure of activity, called non-exercise activity thermogenesis (NEAT). Previous studies have shown that high-capacity running rats (HCR) are lean compared to low-capacity runners (LCR), which are susceptible to cardiovascular disease and metabolic syndrome. Here, we examine the effect of diet on spontaneous activity and NEAT, as well as potential mechanisms underlying these traits, in rats selectively bred for high or low intrinsic aerobic endurance capacity. Compared to LCR, HCR were resistant to the sizeable increases in body mass and fat mass induced by a high-fat diet; HCR also had lower levels of circulating leptin. HCR were consistently more active than LCR, and had lower fuel economy of activity, regardless of diet. Nonetheless, both HCR and LCR showed a similar decrease in daily activity levels after high-fat feeding, as well as decreases in hypothalamic orexin-A content. The HCR were more sensitive to the NEAT-activating effects of intra-paraventricular orexin-A compared to LCR, especially after high-fat feeding. Lastly, levels of cytosolic phosphoenolpyruvate carboxykinase (PEPCK-C) in the skeletal muscle of HCR were consistently higher than LCR, and the high-fat diet decreased skeletal muscle PEPCK-C in both groups of rats. Differences in muscle PEPCK were not secondary to the differing amount of activity. This suggests the possibility that intrinsic differences in physical activity levels may originate at the level of the skeletal muscle, which could alter brain responsiveness to neuropeptides and other factors that regulate spontaneous daily activity and NEAT.     

Effect of hyperthyroidism on spontaneous physical activity and energy expenditure in rats.

Thyroid hormone excess is associated with increased energy expenditure. The contributions of increases in spontaneous physical activity and nonexercise activity thermogenesis (NEAT) to this effect have not been defined. To address the hypothesis that hyperthyroidism is associated with increased spontaneous physical activity and NEAT, we rendered rats hyperthyroid by using continuous infusion of high-dose triiodothyronine for 14 days and measured the effects on physical activity and NEAT. On day 14, in the hyperthyroid group the mean +/- SD triiodothyronine concentration was 755 +/- 137 (range 574-919) ng/dl and in the control group 59 +/- 0.5 (58-59) ng/dl. Over the 14-day treatment period, mean spontaneous physical activity increased in the hyperthyroid rats from 24 +/- 7 to 36 +/- 6 activity units (AU)/min; P < 0.001 but did not increase in the controls (23 +/- 7 vs. 22 +/- 4 AU/min). Also, over the 14-day period, daily NEAT increased in the hyperthyroid rats from 8.1 +/- 2.8 to 19.7 +/- 5.0 kcal/day (P < 0.001) but did not increase in the controls (8.7 +/- 3.5 cf 9.4 +/- 1.7 kcal/day; not significant). In conclusion, hyperthyroidism is associated with increased spontaneous physical activity and NEAT.     

Pedometer and Human Energy Balance Applications for Science Instruction

Teachers can use pedometers to facilitate inquiry learning and show students the need for mathematics in scientific investigation. The authors conducted activities with secondary students that investigated intake and expenditure components of the energy balance algorithm, which led to inquiries about pedometers and related data. By investigating the accuracy of pedometers and variables that may impact reported step counts, students can better understand experimental design and statistical concepts. Students can also examine other data (distance walked, kilocalories expended) using multifunction pedometers and apply the concepts of correlation and regression. This topic fits well with thematic learning and responds to concerns about excess energy intake and insufficient physical activity in the U.S. population.     

High-volume exercise program in obese bariatric surgery patients: a randomized, controlled trial

Weight regain is a problem among many bariatric surgery patients. Whether a high-volume exercise program (HVEP), a strategy to limit weight regain, is feasible in these patients is unknown. The feasibility of an HVEP in obese post-bariatric-surgery patients was determined by randomizing 33 Roux-en-Y gastric bypass (RYGB) and gastric banding (GB) surgery patients with a mean BMI of 41 ± 6 kg/m2 to an HVEP or control group for 12 weeks. The HVEP group was instructed to expend ≥ 2,000 kcal/week in moderate-intensity exercise. All patients were counseled to limit energy intake. Treatment effect was assessed by repeated measures analysis. During the last 4 weeks of the study, 53% of the HVEP group expended ≥ 2,000 kcal/week and 82% expended ≥ 1,500 kcal/week. Step count, reported time spent and energy expended during moderate physical activity, maximal oxygen consumption relative to weight, and incremental area under the postprandial blood glucose curve were significantly improved over 12 weeks in the HVEP group compared to controls (group-by-week effect: P = 0.009-0.03). Both groups reported significant improvement in some quality-of-life scales. Changes in weight, energy and macronutrient intake, resting energy expenditure (REE), fasting lipids and glucose, and fasting and postprandial insulin concentrations were not different between the two groups. HVEP is feasible in about 50% of the patients and enhances physical fitness and reduces postprandial blood glucose in bariatric surgery patients.     

Abnormalities of Energy Expenditure and the Development of Obesity

The role of energy expenditure in the development of obesity remains unclear. This issue is examined using data from prospective studies of energy expenditure and obesity, the effects of overfeeding and diet composition on energy expenditure, and studies of the relationship between energy expenditure for physical activity and body composition. The combined results from these investigations strongly support the view that low energy expenditure can facilitate rapid weight gain in susceptible individuals. It is speculated that, in susceptible individuals, low energy expenditure for resting energy expenditure as well as physical activity are part of a range of mechanisms available for providing surplus energy for rapid weight gain. In addition, both cross-sectional and intervention studies indicate that there is an equilibration between the level of energy expenditure for physical activity and body fat content. While genetic and other factors clearly play an important role in this relationship, it appears that a modest reduction in body fat content can be achieved by increasing energy expenditure for physical activity in physical exercise programs.     

Energetic costs of activity by lizards in the field

1. The available data related to the activity energetics of lizards in the field were collated with respect to three indices of activity energetics: the ecological cost of transport (ECT) expressed as a percentage of the total energy, the proportion of total energy used in all forms of activity (%AR), and the sustained metabolic scope (SusMS), defined as the ratio of the total energy expenditure to the total resting metabolism.
2. The ECT values of lizards ranged from 3 to 36% with five of 11 species having values >20%. The percentage AR ranged from 23 to 80% for lizards during active seasons, with most species having values > 50%. The SusMS ranged from 1·1 to 5·1.
3. Values of ECT are higher for lizards than for mammals, in part because the costs of maintenance metabolism are higher in mammals.
4. The percentage AR and SusMS values of mammals are higher than those of lizards.
5. It follows from the previous two points that the proportion of the total daily energy that is expended in non-locomotory activities is disproportionately higher in mammals compared with lizards.
6. The energy expended in locomotion is a significant portion of the energy budget of lizards. This is generally true for all seasons in which there is activity.     

Energy Expenditure in Lean and Obese Prepubertal Children

The relationship between energy expenditure and obesity was examined in prepubertal children. Consenting fifth graders underwent Tanner Staging, weight, height and skinfold measurements. Subjects were selected for further study to obtain equal numbers of girls and boys with a wide range of body composition. Weight, total daily energy expenditure (TDEE) by doubly labeled water (DLW), resting metabolic rate (RMR), and body composition were measured. Children were grouped into level of obesity based on tertiles of subscapular plus triceps skinfolds. The skinfold tertiles did quite well in grouping subjects by degree of obesity, as differences in percent fat in each tertile were significantly different. There were no differences in fat-free mass between the groups, while the highest tertile group weighed 14 kg more than the lowest. For DLW, energy expenditure was calculated using day 8 and day 9 urine samples as the final time point to examine precision. Mean energy expenditure using either day was nearly identical (2220 ± 400 vs. 2300 ± 370 kcal/d), with a CV of the difference of 5.5%. No differences in RMR, energy expended in activity, or TDEE between the three groups were observed. A reduction in RMR or TDEE could not explain differences in obesity in these prepubertal children. However, the fact that the heaviest children expended the same amount of energy in activity and had the same TDEE as the leanest, while weighing 14 kg more, indicates that the obese children had a reduced activity level.     

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.     

Physical activity and muscle function but not resting energy expenditure impact on weight gain

Understanding whether metabolic factors are predictive of weight gain is important for developing strategies for prevention of weight gain. Recent research has shown that sleeping and resting energy expenditure are not predictive of weight gain. However, exercise endurance, muscular strength, (31)P MRS muscle metabolic economy, and maximum oxygen uptake are independently related to weight gain. Activity-related energy expenditure and the time spent in physical activity are also related to weight gain, with low physical activity explaining approximately 77% of weight gain at 1 year. In addition, weight maintainers spend 80 minutes per day, whereas weight gainers spend less than 20 minutes per day in physical activity equivalent to an intensity of about 4 METS. It is proposed that strength, aerobic fitness, and physical activity are important factors for reducing the rate of weight gain. Although further research is required, these results are suggestive that weight maintenance programs will be more successful if some relatively high-intensity training is included to complement large amounts of low to moderate intense physical activity.     

Physical Activity Level of Urban Pregnant Women in Tianjin,China: A Cross-Sectional Study

Objective

To determine the physical activity level and factors influencing physical activity among pregnant urban Chinese women.

Methods

This prospective cross-sectional study enrolled 1056 pregnant women (18–44 years of age) in Tianjin, China. Their socio-demographic characteristics were recorded, and the Pregnancy Physical Activity Questionnaire was used to assess their physical activity during pregnancy. The data were analyzed by multinomial logistic regression with adjustment for potential confounders.

Results

Median total energy expenditure of pregnant women in each of the three trimesters ranged from 18.50 to 21.90 metabolic equivalents of task (METs) h/day. They expended 1.76–1.85 MET h/day on moderate and vigorous activities and 0.11 MET h/day on exercise. Only 117 of the women (11.1%) met the international guideline for physical activity in pregnancy (≥150 min moderate intensity exercise per week). The most frequent reason given for not being more physically active was the fear of miscarriage. Higher education level (OR: 4.11, 95% CI: 1.59–10.62), habitual exercise before pregnancy (OR: 2.14, 95% CI: 1.39–3.28), and husbands who exercised regularly (OR: 2.21, 95% CI: 1.33–3.67) significantly increased the odds of meeting the guideline (p<0.001). A low pre gravid body mass index (OR: 0.42, 95% CI: 0.20–0.87) significantly decreased the odds (p<0.001).

Conclusions

Few urban Chinese pregnant women met the recommended physical activity guideline. They also expended little energy exercising. Future interventions should be based on the clinic environment and targeting family members as well as the subjects. All pregnant women should be targeted, not just those in high-risk groups.     

It costs to be clean and fit: energetics of comfort behavior in breeding-fasting penguins

Background

Birds may allocate a significant part of time to comfort behavior (e.g., preening, stretching, shaking, etc.) in order to eliminate parasites, maintain plumage integrity, and possibly reduce muscular ankylosis. Understanding the adaptive value of comfort behavior would benefit from knowledge on the energy costs animals are willing to pay to maintain it, particularly under situations of energy constraints, e.g., during fasting. We determined time and energy devoted to comfort activities in freely breeding king penguins (Aptenodytes patagonicus), seabirds known to fast for up to one month during incubation shifts ashore.

Methodology/Principal Findings

A time budget was estimated from focal and scan sampling field observations and the energy cost of comfort activities was calculated from the associated increase in heart rate (HR) during comfort episodes, using previously determined equations relating HR to energy expenditure. We show that incubating birds spent 22% of their daily time budget in comfort behavior (with no differences between day and night) mainly devoted to preening (73%) and head/body shaking (16%). During comfort behavior, energy expenditure averaged 1.24 times resting metabolic rate (RMR) and the corresponding energy cost (i.e., energy expended in excess to RMR) was 58 kJ/hr. Energy expenditure varied greatly among various types of comfort behavior, ranging from 1.03 (yawning) to 1.78 (stretching) times RMR. Comfort behavior contributed 8.8–9.3% to total daily energy expenditure and 69.4–73.5% to energy expended daily for activity. About half of this energy was expended caring for plumage.

Conclusion/Significance

This study is the first to estimate the contribution of comfort behavior to overall energy budget in a free-living animal. It shows that although breeding on a tight energy budget, king penguins devote a substantial amount of time and energy to comfort behavior. Such findings underline the importance of comfort behavior for the fitness of colonial seabirds.     

Impulsive Approach Tendencies towards Physical Activity and Sedentary Behaviors,but Not Reflective Intentions,Prospectively Predict Non-Exercise Activity Thermogenesis

Understanding the determinants of non-exercise activity thermogenesis (NEAT) is crucial, given its extensive health benefits. Some scholars have assumed that a proneness to react differently to environmental cues promoting sedentary versus active behaviors could be responsible for inter-individual differences in NEAT. In line with this reflection and grounded on the Reflective-Impulsive Model, we test the assumption that impulsive processes related to sedentary and physical activity behaviors can prospectively predict NEAT, operationalized as spontaneous effort exerted to maintain low intensity muscle contractions within the release phases of an intermittent maximal isometric contraction task. Participants (n = 91) completed a questionnaire assessing their intentions to adopt physical activity behaviors and a manikin task to assess impulsive approach tendencies towards physical activity behaviors (IAPA) and sedentary behaviors (IASB). Participants were then instructed to perform a maximal handgrip strength task and an intermittent maximal isometric contraction task. As hypothesized, multilevel regression analyses revealed that spontaneous effort was (a) positively predicted by IAPA, (b) negatively predicted by IASB, and (c) was not predicted by physical activity intentions, after controlling for some confounding variables such as age, sex, usual PA level and average force provided during the maximal-contraction phases of the task. These effects remained constant throughout all the phases of the task. This study demonstrated that impulsive processes may play a unique role in predicting spontaneous physical activity behaviors. Theoretically, this finding reinforces the utility of a motivational approach based on dual-process models to explain inter-individual differences in NEAT. Implications for health behavior theories and behavior change interventions are outlined.     

Body weight,energy metabolism,and time in the life of birds

The breeding of birds, both large and small, is affected by two specific factors: (1) hypometry of egg weight relative to female body weight and (2) seasonality of breeding, with the favorable period being limited and almost equal for birds of different body sizes. Dozens of published allometric formulas describing the dependence of energy parameters of eggs and nestlings at different growth stages and the energy cost of parental care on the body weight of parents, eggs, and nestlings, respectively, are reviewed. It is shown that birds, especially species with a large body weight, repeatedly change their metabolic parameters during ontogeny in order to shorten the period of breeding and growth. In most species, the energy costs of breeding in both sexes are approximately equal. Bringing food in the bill allows birds to supply nestlings with the amount of energy that is dozens of times greater than that expended for obtaining the food. In placental mammals, only females are involved in offspring development. Therefore, the growth rate of embryos and energy expenditures for milk feeding are limited by the metabolic potential of the mother. As a consequence, mammalian offspring grow ten times slower than bird nestlings, the body weights of females being equal.     

Energy of ligand-RNA complex formation

This work presents an energetic analysis of complex formation of eleven ligands with different structure and charge with RNA aptamers. The most entire set of the components of the total Gibbs energy of complex formation has been first calculated using different physical factors: van der Waals, electrostatic and hydrophobic interactions, hydrogen bonds and specific factors being predominantly of entropic character. The calculated Gibbs energy is found to be in a good agreement with experimental data. Different energy components which stabilize and destabilize complexes are lined up according to the degree of importance. The results obtained provide an understanding of the role of different physical interactions in a ligand-RNA complex formation.