Spontaneous Physical Activity Levels Research Articles

Multidisciplinary analysis of cancer-related fatigue at the time of diagnosis: preliminary results of the BIOCARE FActory cohort.

Cancer-related fatigue (CRF) is a common side effect of cancer and cancer treatment that significantly impairs the quality of life and can persist for years after treatment completion. Although fatigue is often associated with cancer treatment, it is also a result of the disease itself, even before intervention. CRF at the time of diagnosis may affect treatment timing or completion and is a consistent predictor of post-treatment fatigue at any time. The mechanisms underlying CRF are multidimensional and not well understood, particularly at the time of diagnosis. Sixty-five breast cancer patients at the time of diagnosis were included. The participants completed self-assessment questionnaires about CRF, sleep disturbances, and emotional symptoms and wore an accelerometer to assess levels of spontaneous physical activity and sleep quality. During the experimental session, the participants underwent cognitive, neuromuscular, and exercise metabolism evaluations. Using augmented backward elimination regression, this study found that emotional symptoms and perceived sleep disturbances were the strongest predictors of CRF (adjusted r2 = 0.51). Neuromuscular fatigability and sleep disturbance were also associated with physical dimensions, whereas cognitive performance was associated with cognitive dimensions. At the time of diagnosis, emotional and cognitive dimensions are over-represented compared to the general population, and specific subdimensions have specific predictors that support the idea of distinct mechanisms. Evaluating CRF subdimensions and their potential mechanisms at the time of diagnosis would be particularly relevant for identifying high-risk patients and offering them appropriate interventions. This study was registered at ClinicalTrials.gov (NCT04391543) in May, 2020.

Exercise interventions for older people at risk for frailty: A protocol for systematic review and meta-analysis.

Background:Frailty is a state of age-related reduced physiological reserve characterized by an increased risk of adverse clinical outcomes. Studies have shown that exercise can improve frailty in older people. However, it remains to be seen which exercises will most improve the fitness of older people with frailty or those at the risk for frailty.Objective: This protocol aims to determine whether physical exercise can improve frailty in older people, and if which methods are most effective.Methods:We searched the following databases for relevant articles published between January 1, 2012 and January 1, 2021: PubMed, EMBASE, the Cochrane Library, Wanfang, the China National Knowledge Infrastructure, Clinical Trials Database, and the Science Network. Two independent reviewers will carry out data extraction, discuss and resolve differences, and obtain consensus from the third author. We will select randomized control trials (RCTs) according to the preformulated inclusion criteria. The main outcomes in this study are scores from Fried Frailty Phenotype Criteria; the Frailty Trait Scale–short form; the SHARE Frailty Instrument; the FRAIL scale; the Gérontopôle Frailty Screening Tool; the Clinical Frailty Scale, the Rockwood and Mitnitsky Frailty Index; the Study of Osteoporotic Fractures Index; the Edmonton Frailty Scale; the Fatigue, Resistance, Ambulation, Illness and Loss of Weight Index; the Multidimensional Prognostic Index; the Tilburg Frailty Indicator; PRISMA-7; the Groningen Frailty Indicator; the Sherbrooke Postal Questionnaire; and the Kihon Checklist. Secondary outcomes are muscle strength, gait velocity, stair-climbing power, and level of spontaneous physical activity. If the heterogeneity test shows slight or no statistical heterogeneity, a fixed effects model will be used for data synthesis; otherwise, a random effects model will be used. We will develop a unified data extraction table that includes a number of parameters. The Cochrane Cooperative Bias Risk Tool will be used to evaluate the methodological quality of the selected RCTs. RevMan Manager 5.3 and STATA 14.0 will be used for data analysis if enough RCTs (more than 10) are identified and selected.Result:The final results will provide information on the effectiveness of intervention programs for frail older adul and further demonstrate which exercise programs are more effective and which methods can significantly improve frailty.Conclusion:This protocol will contribute to the development of more effective interventions for elderly individuals with frailty.Ethics and dissemination:This study applies existing literature references; therefore, ethical approval is not required.INPLASY registration number:INPLASY202130107

Effect of resveratrol, carnitin, quercetin and aromatic amino acids on the xenobiotic metabolising and antioxidant enzymes in the liver during obesity in rats with different genotypes

The use of minor biologically active substances (BAS) in specialized products is one of the promising areas in the diet therapy for obesity and other alimentary-dependent diseases (metabolic syndrome, type 2 diabetes mellitus, etc.). The effects of the BAS in patients are often ambiguous, depending on a number of factors, one of which is the state of the organism enzyme systems (enzymes of xenobiotic metabolism and antioxidant defense), the patient's genotype, and many others. The aim was to study the effect of BAS [quercetin (Q), L-carnitine (L-Car), resveratrol (Res), aromatic amino acids tyrosine (Tyr) and tryptophan (Trp)] on the activities of phase I and II of xenobiotic-metabolising enzymes and antioxidant enzymes in rats using various in vivo models of obesity and with impaired dopamine transport. Material and methods. The activities of cytochrome P450 enzymes (CYP1A1 and CYP3A), glutathione transferase (GT), UDPglucuronosyltransferase (UDP-GT), hemoxygenase-1 (HO-1), and quinone reductase (QR) were determined by fluorimetric, spectrophotometric methods and HPLC in microsomes and cytosolic fraction of rat's liver. We used rats of outbred Wistar line, Zucker ZF line with hereditarily determined obesity and DAT-KO line with a knockout of the DAT dopamine transporter gene, which for 62 days were fed a standard balanced control or high-carbohydrate high-fat diet (30% fat by weight and 20% fructose solution instead of water) supplemented with BAS, such as Q, Res, L-Car, Tyr and Trp in doses 50, 25, 300, 1250 and 250 mg/kg of body weight respectively. Results and discussion. The presence of a DAT knockout led to a small but statistically significant decrease in the activity of GT in the liver in both homozygous and heterozygous animals. The CYP1A1 activity was significantly decreased in all carriers of the DAT knockout gene, while HO-1 activity, on the contrary, was increased, independently of the composition of the diet used. In Zucker ZF rats of all groups, in comparison with Wistar rats fed the corresponding diets, the activities of GT, UDP-GT, CYP1A1, CYP3A and QR were significantly reduced in terms of the total protein content. HO-1 activity was reduced in Zucker ZF rats in comparison with Wistar rats to a lesser extent, however, the addition of Q significantly influenced the difference between the two lines. Trp consumption led to a significant increase in GT activity in Wistar rats. In DAT-KO homozygotes this effect was insignificant, while in heterozygotes it was absent. Similarly, consumption of Trp resulted in a significant increase in CYP1A1 activity only in Wistar rats, but not in DAT-KO rats. The activity of UDP-GT under Trp intake increased only in DAT heterozygotes. The genotype significantly influenced the response of QR activity to Trp consumption, but in an ambiguous way - there was an increase in activity in heterozygotes and a decrease in homozygotes for DAT knockout. CYP1A1 activity was significantly increased in rats treated with Tyr. Conclusion. The data obtained indicate that the effect of various dietary supplements used in the treatment of obesity and metabolic syndrome on the xenobiotic-metabolising enzymes and antioxidant enzymes can have a different nature and direction depending on the genotype and the level of spontaneous physical activity and energy expenditure determined by it, which should be taken into account when approaches to personalized diet therapy of alimentary-dependent diseases are developing.

Can regular physical activity prevent obesity? 3: Empirical longitudinal evidence of its efficacy.

Objective. The objective of this narrative review is to examine longitudinal data pointing to the efficacy of adequate daily physical activity in the prevention of obesity. Methods. Information obtained from Ovid/Medline, Pub-Med and Google Scholar through to April 2019 has been supplemented by a search of the author's extensive personal files. Results. Babies that have a high level of spontaneous physical activity generally accumulate less body fat then their peers over the first few years of life. However, there is little evidence of a favourable response to supplementary exercise programmes in pre-school children, perhaps because of practical difficulties in augmenting habitual physical activity in this age group. Summer camps for older children usually induce a substantial immediate decrease of both body mass and tissue fat stores, but it is unclear how far this reflects dietary restrictions at the camp rather than an increase of physical activity in this environment. Five of 8 uncontrolled longitudinal studies of children and adolescents with subjective assessments of habitual physical activity found no beneficial changes of body composition in individuals who were physically more active, as opposed to 3 positive reports (one of these seeing benefits in girls only). However, perhaps because more accurate categorization of exercise levels was possible, benefit was demonstrated in 8 of 10 trials of children with objective assessments of habitual physical activity. Fifteen of 26 trials of children and adolescents with group programme assignment also found a better body composition in those assigned to groups that were more physically active, although participants in 9 of thes 15 trials were given not only an increase of physical activity, but also dietary advice and/or a restriction of food intake. Cohort studies in adults have found fairly consistently that regular physical activity reduces obesity or prevents the increase of body fat content usually associated with aging; benefit was seen in 14 of 17 studies of young adults, and 20 of 21 groups of middle-aged and older individuals. The portion of the day allocated to sedentary behaviour has also been associated with the development of obesity in 4 of 6 studies in children, and 10 of 13 trials in adults. Likewise, the transition from physically active hunting and gathering to an urban lifestyle has been associated with an accumulation of body fat in arctic Inuit. In children, randomized controlled trials have shown beneficial changes in body composition from interventions only when the intervention has been effective in achieving a substantial increase of daily physical activity. However 27 of 31 controlled studies of adults have demonstrated a reduction of body fat content in response to a variety of exercise initiatives. It is more difficult to assign a vigorous exercise programme to the frail elderly, and in this age group there has as yet been little study of the potential to reduce body fat by an increase in physical activity, although this would confer obvious functional benefit on those with limited muscle strength. Conclusions. Both in children and in adults, the bulk of prospective and controlled trials point to the efficacy of adequate volumes of regular exercise in both the prevention and the control of obesity. But as with initiatives based on rigorous dieting, the challenge to health professionals is to sustain the enthusiasm of clients over a sufficient period for a programme to take effect and to become a part of the individual's normal lifestyle.

SAT-389 Evaluation of the Hypothalamic-Pituitary-Adrenal Axis and Physical Performance in Older Adults

INTRODUCTION: Blunting of the circadian rhythm of the hypothalamic–pituitary– adrenal (HPA) axis is known to occur with aging, although a pathological overall increase in glucocorticoid secretion is rare in elderly. Persistently high levels of cortisol are associated with increased catabolism of skeletal muscle, so that a link between chronically elevated cortisol and frailty is biologically plausible in this population. OBJECTIVE: We aimed to investigate the relationships between the activity of the HPA axis, determined the diurnal cortisol release pattern and DHEA secretion, and physical performance in older adults. METHODS: A total of 69 elderly (65.2% female), aged 60-84 years, with normal cognition and functionally healthy, with a median BMI of 27.3 kg/m2 (ranging from 19.1 to 38.6), were enrolled. Physical performance was tested by: a) number of steps per day measured by a pedometer during 3 consecutive working days; b) Sitting-Rising Test (SRT); c) Single-Leg Stance (SLS); d) Timed Up and Go (TUG); e) One-Repetition Maximum Test (1RM); f) Six Minute Walk Test (6MWT). Individuals were considered active when mean daily steps was ≥7,000 steps, and insufficiently active when <7,000 steps. Salivary cortisol (sC) was collected 30min after awakening, at 11 a.m., 5 p.m. and 9 p.m. and before bedtime in the third day of the pedometer use, and blood samples for serum DHEA concentration were collected on a subsequent day. Non-parametric Mann-Whitney test and Spearman correlation test, when applicable, were used for statistical analysis. Area under curve (AUC) was calculated for determination of the diurnal cortisol release pattern. RESULTS: A total of 41 individuals (59.4%) were classified as insufficiently active, and 28 as active (40.6%), according to pedometer-assessed steps per day. Active elderly exhibited a better balance and performance in the 1RM Test (p=0,05) than inactive. A worse performance in the 1RM Test was observed in individuals with higher sC at 11 a.m and in those with a larger AUC of sC (p<0,05). In addition, individuals with lower serum DHEA concentration exhibited a worse performance at the 6MWT (p=0.03). CONCLUSION: Our findings support the association between spontaneous physical activity levels, assessed by the pedometer daily steps measurement, and functional performance in elderly. In addition, higher diurnal cortisol secretion and lower DHEA plasmatic levels were associated with a lower physical performance in older individuals.

Breast cancer: effectiveness of a one-year unsupervised exercise program.

Improvements in prevention and therapeutic strategies over the years have considerably increased the number of breast cancer survivors. Sedentary behavior is now acknowledged to be a risk factor for cancer and cancer relapse. Currently, there are different approaches to increasing the effectiveness of long-term physical activity in these patients. The aim of this study was to verify the long-term effectiveness of a home-based program for active lifestyle change in overweight breast cancer survivors. We enrolled 43 women (age 51.5±9.9 years), who underwent an evaluation of their spontaneous physical activity levels, their baseline aerobic capacity through a 6-Minute Walking Test (6MWT), their flexibility, grip and lower limb strength, and their body composition. We repeated the measurements of these physical and anthropometric parameters six times during one year of unsupervised exercise. At the beginning of the program the sample showed a moderate level of spontaneous physical activity (physical activity level=1.44±0.12, steps/day=7420.3±1622.3). After being prescribed an individual exercise program, a significant reduction in BMI (T0=27.9±4.3, T5=25.8±3.0 kg/m2; P<0.001) and skinfold sum was observed (T0=99.5±25.2, T5=86.2±22.7 mm; P=0.019), with a parallel maintenance of cell mass (T0= 21.4±3.3, T5= 22.5±3.0 kg; P=0.654). The functional parameters showed an increase in lower limb muscle fitness and a reduction in diastolic blood pressure after 6 MWT (T0= 78.4±10.1, T5= 72.5±14.9 mmhg; P=0.032). Physical activity is recommended for cancer patients; this model of prescribing unsupervised exercise seems to ensure optimal compliance, thus allowing long-term therapeutic efficacy.

Selection for high aerobic capacity has no protective effect against obesity in laboratory mice

Aerobic capacity (VO2max measured during intensive physical exercise) both trained and intrinsic (i.e. genetically determined) has recently been deemed a good predictor of cardiometabolic risks. However, the underlying mechanisms linking VO2max and health risk factors are not entirely clear, as it seems that not VO2max per se, but rather some correlated traits, like spontaneous physical activity (SPA) are responsible for sustaining the lean phenotype. Here we investigated the link between genetically determined aerobic capacity, SPA and resistance to diet-induced health risks using replicated lines of mice selected for high aerobic capacity during swimming in mid-cold water (25°C) and Randomly Bred control mice. After four months of consumption of the western type HFat and HCarb diets and no forced nor voluntary training, we found no evidence of protective effects of intrinsic high VO2max. The Selected mice displayed similar levels of blood glucose, cholesterol, triglycerides and body fat as the Random Bred control animals. Most notably we found no correlation between VO2max and SPA levels. Our results therefore call into question the ubiquity of VO2max as a predictor of metabolic health and leanness, at least in animal models.

Role of spontaneous physical activity in prediction of susceptibility to activity based anorexia in male and female rats

Anorexia nervosa (AN) is a chronic eating disorder affecting females and males, defined by body weight loss, higher physical activity levels and restricted food intake. Currently, the commonalities and differences between genders in etiology of AN are not well understood. Animal models of AN, such as activity-based anorexia (ABA), can be helpful in identifying factors determining individual susceptibility to AN. In ABA, rodents are given an access to a running wheel while food restricted, resulting in paradoxical increased physical activity levels and weight loss. Recent studies suggest that different behavioral traits, including voluntary exercise, can predict individual weight loss in ABA. A higher inherent drive for movement may promote development and severity of AN, but this hypothesis remains untested. In rodents and humans, drive for movement is defined as spontaneous physical activity (SPA), which is time spent in low-intensity, non-volitional movements. In this paper, we show that a profile of body weight history and behavioral traits, including SPA, can predict individual weight loss caused by ABA in male and female rats with high accuracy. Analysis of the influence of SPA on ABA susceptibility in males and females rats suggests that either high or low levels of SPA increase the probability of high weight loss in ABA, but with larger effects in males compared to females. These results suggest that the same behavioral profile can identify individuals at-risk of AN for both male and female populations and that SPA has predictive value for susceptibility to AN.

The health impact of sedentary behaviour in children and youth

Emerging evidence suggests that sedentary behaviour is independently associated with cardiometabolic disease risk in school-aged children and youth. This thesis includes 4 related studies in the pursuit of 2 objectives: (i) To determine the cross-sectional association of sedentary time, interruptions in sedentary time, sedentary bout length, and total movement variability with markers of cardiometabolic disease risk among children and youth; and (ii) to examine the impact of 1-day of prolonged sedentary behaviour, with and without interruptions or structured physical activity, on markers of cardiometabolic disease risk, hunger, food intake and spontaneous physical activity levels in children and youth. In Study 1, we found that interruptions in sedentary time and short bouts of sedentary time were beneficially associated with clustered cardiometabolic disease risk in boys and girls aged 8–11 years, independent of total sedentary time, moderate-and-vigorous physical activity (MVPA), and other confounders (all p &lt; 0.05), while the opposite was true for screen-based sedentary behaviours. In Study 2, we found that movement variability (minute-to-minute changes in movement intensity) was negatively associated with clustered cardiometabolic disease risk and systolic blood pressure independent of MVPA, sedentary time and other covariates in a representative sample of American children and youth aged 12–17 years (all p &lt; 0.05). In Studies 3 and 4, we found that prolonged sitting, with or without interruptions and structured MVPA, did not result in acute changes in markers of cardiometabolic disease risk or subsequent ad libitum food intake or physical activity levels in healthy children aged 10–14 years (all p ≥ 0.05). Taken together, the studies that make up this thesis suggest that optimal levels of cardiometabolic disease risk are most likely to be seen in children who limit their time engaging in screen-based sedentary behaviours, who frequently interrupt their sedentary time, and who have high levels of variability in their movement behaviours.

The Health Impact of Sedentary Behaviour In Children and Youth

Emerging evidence suggests that sedentary behaviour is independently associated with cardiometabolic disease risk in school-aged children and youth. This thesis includes 4 related studies in the pursuit of 2 objectives: (i) To determine the cross-sectional association of sedentary time, interruptions in sedentary time, sedentary bout length, and total movement variability with markers of cardiometabolic disease risk among children and youth; and (ii) to examine the impact of 1-day of prolonged sedentary behaviour, with and without interruptions or structured physical activity, on markers of cardiometabolic disease risk, hunger, food intake and spontaneous physical activity levels in children and youth. In Study 1, we found that interruptions in sedentary time and short bouts of sedentary time were beneficially associated with clustered cardiometabolic disease risk in boys and girls aged 8–11 years, independent of total sedentary time, moderate-and-vigorous physical activity (MVPA), and other confounders (...

Mechanisms underlying obesity resistance associated with high spontaneous physical activity

Obesity resistance due to elevated orexin signaling is accompanied by high levels of spontaneous physical activity (SPA). The behavioral and neural mechanisms underlying this observation have not been fully worked out. We determined the contribution of hypothalamic orexin receptors (OXRs) to SPA stimulated by orexin A (OXA), whether OXA-stimulated SPA was secondary to arousal and whether voluntary wheel running led to compensations in 24-h SPA. We further tested whether orexin action on dopamine one receptors (DA1R) in the substantia nigra (SN) plays an important role in the generation of SPA. To test this, SPA response was determined in lean and obese rats with cannulae targeted toward the rostral lateral hypothalamus (rLH) or SN. Sleep/wake states were also measured in rats with rLH cannula and electroencephalogram/electromyogram radiotelemetry transmitters. SPA in lean rats was more sensitive to antagonism of the OX1R and in the early response to the orexin 2 agonist. OXA increased arousal equally in lean and obese rodents, which is discordant from the greater SPA response in lean rats. Obesity-resistant rats ran more and wheel running was directly related to 24-h SPA levels. The OX1R antagonist, SB-334867-A, and the DA1R antagonist, SCH3390, in SN more effectively reduced SPA stimulated by OXA in obesity-resistant rats. These data suggest OXA-stimulated SPA is not secondary to enhanced arousal, propensity for SPA parallels inclination to run and that orexin action on dopaminergic neurons in SN may participate in the mediation of SPA and running wheel activity.

Physical fitness level and movement skills of 7 year old girls depending on their physical activities and hyperactivity problems

Introduction: The problem of physical hyperactivity is currently one of the most common developmental issues faced by children. Spontaneous physical activity becomes one of the possible techniques which helps a hyperactive child control her energy. The goal of the research study was to determine the level of motor skills and the degree of mastering simple physical tasks by girls with various levels of spontaneous physical activity and hyperactivity disorder as compared to their peers who do not exhibit such problems.

The Effects of Overfeeding on Spontaneous Physical Activity in Obesity Prone and Obesity Resistant Humans

Despite living in an environment that promotes weight gain in many individuals, some individuals maintain a thin phenotype while self-reporting expending little or no effort to control their weight. When compared with obesity prone (OP) individuals, we wondered if obesity resistant (OR) individuals would have higher levels of spontaneous physical activity (SPA) or respond to short-term overfeeding by increasing their level of SPA in a manner that could potentially limit future weight gain. SPA was measured in 55 subjects (23 OP and 32 OR) using a novel physical activity monitoring system (PAMS) that measured body position and movement while subjects were awake for 6 days, either in a controlled eucaloric condition or during 3 days of overfeeding (1.4 × basal energy) and for the subsequent 3 days (ad libitum recovery period). Pedometers were also used before and during use of the PAMS to provide an independent measure of SPA. SPA was quantified by the PAMS as fraction of recording time spent lying, sitting, or in an upright posture. Accelerometry, measured while subjects were in an upright posture, was used to categorize time spent in different levels of movement (standing, walking slowly, quickly, etc.). There were no differences in SPA between groups when examined across all study periods (P > 0.05). However, 3 days following overfeeding, OP subjects significantly decreased the amount of time they spent walking (-2.0% of time, P = 0.03), whereas OR subjects maintained their walking (+0.2%, P > 0.05). The principle findings of this study are that increased levels of SPA either during eucaloric feeding or following short term overfeeding likely do not significantly contribute to obesity resistance although a decrease in SPA following overfeeding may contribute to future weight gain in individuals prone to obesity.

Deletion of Nhlh2 Results in a Defective Torpor Response and Reduced Beta Adrenergic Receptor Expression in Adipose Tissue

BackgroundMice with a targeted deletion of the basic helix-loop-helix transcription factor, Nescient Helix-Loop-Helix 2 (Nhlh2), display adult-onset obesity with significant increases in their fat depots, abnormal responses to cold exposure, and reduced spontaneous physical activity levels. These phenotypes, accompanied by the hypothalamic expression of Nhlh2, make the Nhlh2 knockout (N2KO) mouse a useful model to study the role of central nervous system (CNS) control on peripheral tissue such as adipose tissue.MethodologyDifferences in body temperature and serum analysis of leptin were performed in fasted and ad lib fed wild-type (WT) and N2KO mice. Histological analysis of white (WAT) and brown adipose tissue (BAT) was performed. Gene and protein level expression of inflammatory and metabolic markers were compared between the two genotypes.Principal FindingsWe report significant differences in serum leptin levels and body temperature in N2KO mice compared with WT mice exposed to a 24-hour fast, suggestive of a defect in both white (WAT) and brown adipose tissue (BAT) function. As compared to WT mice, N2KO mice showed increased serum IL-6 protein and WAT IL-6 mRNA levels. This was accompanied by slight elevations of mRNA for several macrophage markers, including expression of macrophage specific protein F4/80 in adipose, suggestive of macrophage infiltration of WAT in the mutant animals. The mRNAs for β3-adrenergic receptors (β3-AR), β2-AR and uncoupling proteins were significantly reduced in WAT and BAT from N2KO mice compared with WT mice.ConclusionsThese studies implicate Nhlh2 in the central control of WAT and BAT function, with lack of Nhlh2 leading to adipose inflammation and altered gene expression, impaired leptin response to fasting, all suggestive of a deficient torpor response in mutant animals.

Increased physical activity cosegregates with higher intake of carbohydrate and total calories in a subcongenic mouse strain

C57BL/6 J (B6) and CAST/EiJ (CAST), the inbred strain derived from M. musculus castaneus, differ in nutrient intake behaviors, including dietary fat and carbohydrate consumption in a two-diet-choice paradigm. Significant quantitative trait loci (QTLs) for carbohydrate (Mnic1) and total energy intake (Kcal2) are present between these strains on chromosome (Chr) 17. Here we report the refinement of the Chr 17 QTL in a subcongenic strain of the B6.CAST-( D17Mit19-D17Mit91 ) congenic mice described previously. This new subcongenic strain possesses CAST Chr 17 donor alleles from 4.8 to 45.4 Mb on a B6 background. Similar to CAST, the subcongenic mice exhibit increased carbohydrate and total calorie intake per body weight, while fat intake remains equivalent. Unexpectedly, this CAST genomic segment also confers two new physical activity phenotypes: 22% higher spontaneous physical activity levels and significantly increased voluntary wheel-running activity compared with the parental B6 strain. Overall, these data suggest that gene(s) involved in carbohydrate preference and increased physical activity are contained within the proximal region of Chr 17. Interval-specific microarray analysis in hypothalamus and skeletal muscle revealed differentially expressed genes within the subcongenic region, including neuropeptide W (Npw); glyoxalase I (Glo1); cytochrome P450, family 4, subfamily f, polypeptide 1 (Cyp4f15); phospholipase A2, group VII (Pla2g7); and phosphodiesterase 9a (Pde9a). This subcongenic strain offers a unique model for dissecting the contributions and possible interactions among genes controlling food intake and physical activity, key components of energy balance.

Effect of acute and chronic caloric restriction and metabolic glucoprivation on spontaneous physical activity in obesity-prone and obesity-resistant rats

Caloric restriction (CR) and metabolic glucoprivation affect spontaneous physical activity (SPA), but it's unknown whether these treatments similarly affect SPA in selectively bred obesity-prone (OP) and -resistant (OR) rats. OR rats have greater basal SPA and are more responsive to treatments that modulate SPA, such as orexin A administration. We hypothesized that OR rats would be more sensitive to other treatments modulating SPA. To test this, continuous 24-h SPA was measured before and during acute (24 h) and chronic (8 wk) CR in OR, OP, and Sprague-Dawley rats. Pharmacological glucoprivation was produced by injection of 2-deoxyglucose (2-DG), and SPA was measured 5 h postinjection. Acute CR increased SPA in all groups; however, the effect was dependent on the index of SPA and time interval during the 24-h time period. In contrast to OR rats, chronic CR increased distance traveled, ambulatory episodes, and time spent in ambulation and stereotypy during the time interval preceding anticipation of food in OP and Sprague-Dawley rats. Although the effects of 2-DG treatment on SPA were minimal, OR rats had significantly greater SPA than OP and Sprague-Dawley rats independent of treatment. That chronic CR failed to result in significant changes in SPA in OR rats suggests that these rats may be especially unresponsive to treatments modulating feeding. This insensitivity coupled with elevated basal SPA levels may in part mediate phenotypic traits of lean rats.

Energy metabolism, fuel selection and body weight regulation

Energy homeostasis is critical for the survival of species. Therefore, multiple and complex mechanisms have evolved to regulate energy intake and expenditure to maintain body weight. For weight maintenance, not only does energy intake have to match energy expenditure, but also macronutrient intake must balance macronutrient oxidation. However, this equilibrium seems to be particularly difficult to achieve in individuals with low fat oxidation, low energy expenditure, low sympathetic activity or low levels of spontaneous physical activity, as in addition to excess energy intake, all of these factors explain the tendency of some people to gain weight. Additionally, large variability in weight change is observed when energy surplus is imposed experimentally or spontaneously. Clearly, the data suggest a strong genetic influence on body weight regulation implying a normal physiology in an 'obesogenic' environment. In this study, we also review evidence that carbohydrate balance may represent the potential signal that regulates energy homeostasis by impacting energy intake and body weight. Because of the small storage capacity for carbohydrate and its importance for metabolism in many tissues and organs, carbohydrate balance must be maintained at a given level. This drive for balance may in turn cause increased energy intake when consuming a diet high in fat and low in carbohydrate. If sustained over time, such an increase in energy intake cannot be detected by available methods, but may cause meaningful increases in body weight. The concept of metabolic flexibility and its impact on body weight regulation is also presented.

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.

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.

Modulation of central leptin sensitivity and energy balance in a rat model of diet‐induced obesity

The aim of this study was to further explore the time-dependent changes in leptin sensitivity using a rat model of dietary fat-induced obesity and to investigate the potential mechanisms governing these changes. We used male, adult Sprague-Dawley rats that were fed either a standard laboratory chow diet (3% fat) or a high-saturated fat (HF) diet (60% fat) for 2 or 5 weeks. Energy balance (body weight, energy intake and energy expenditure); sensitivity to central leptin and central alpha-melanin stimulating hormone (alpha-MSH) administration and expression levels of hypothalamic ObRb, signal transducers and activators of transcription factor (STAT)-3 phosphorylation, suppressor of cytokine signalling-3 (SOCS-3), proopiomelanocortin (POMC) processing hormones (prohormone convertase-1 and prohormone convertase-2) and neuropeptide Y (NPY) were measured. After 2 weeks of feeding HF diet, there was an increase in total energy intake (TEI) but a reduction in food intake as measured by the mass of food ingested. Body weight at this time was not significantly different between the two diet groups; however, white adipose tissue (WAT) weight was significantly greater in the HF-fed rats than in the chow-fed rats. In addition, spontaneous physical activity levels were increased, but no changes were observed in resting energy expenditure. Furthermore, chow-fed lean rats responded to central leptin administration by reducing the energy intake by approximately 67 kJ compared with saline treatment (p < 0.05), while the HF-fed diet-induced obese (DIO) rats responded by reducing their energy intake by approximately 197 kJ compared with saline treatment (p < 0.05). After 5 weeks of feeding HF diet, TEI remained significantly higher, body weight was significantly increased by 5% in the HF-fed rats and WAT weight was significantly heavier in HF-fed rats than in the chow-fed lean rats. After leptin treatment, the chow-fed lean rats reduced their energy intake by approximately 97 kJ (p < 0.05); yet, leptin had no significant effect in the HF-fed DIO rats. ObRb protein expression, STAT-3 phosphorylation levels, content and messenger RNA (mRNA) expression of NPY, SOCS-3 mRNA and protein expression and energy intake response to central alpha-MSH administration were not altered after HF diet feeding. These results suggest that early in the course of HF diet-induced weight gain, there was a period of central leptin hypersensitivity, and as the obesity progresses, central leptin insensitivity develops. This insensitivity does not appear to be explained by a downregulation of ObRb protein levels, reduced leptin signalling, an increase in either SOCS-3 or NPY expression or reduced function of the melanocortin system. The effect of an HF diet on other actions of leptin such as its effect on the endocannabinoid system should be investigated.