Spontaneous Physical Activity in Obese Condition Favours Antitumour Immunity Leading to Decreased Tumour Growth in a Syngeneic Mouse Model of Carcinogenesis

Our goal was to evaluate the effect of spontaneous physical activity on tumour immunity during aging. Elderly (n = 10/group, 33 weeks) ovariectomized C57BL/6J mice fed a hyperlipidic diet were housed in standard (SE) or enriched (EE) environments. After 4 weeks, orthotopic implantation of syngeneic mammary cancer EO771 cells was performed to explore the immune phenotyping in the immune organs and the tumours, as well as the cytokines in the tumour and the plasma. EE lowered circulating myostatin, IL-6 and slowed down tumour growth. Spleen and inguinal lymph node weights reduced in relation to SE. Within the tumours, EE induced a lower content of lymphoid cells with a decrease in Th2, Treg and MDCS; and, conversely, a greater quantity of Tc and TAMs. While no change in tumour NKs cells occurred, granzyme A and B expression increased as did that of perforin 1. Spontaneous physical activity in obese conditions slowed tumour growth by decreasing low-grade inflammation, modulating immune recruitment and efficacy within the tumour.

Assessment of the influence of physical activity and screen time on somatic features and physical fitness in 6 to 7-year-old girls

Aim of the study is to assess the relationship between screen time, physical activity and physical fitness among girls 6–7 years-old. 21,528 girls aged 6 and 7 from Poland were assessed in terms of physical fitness. Arm strength, abdominal strength and explosive strength of the lower limbs were measured using the EUROFIT test. Basic somatic features were measured and BMI and WHtR indices were calculated. Spontaneous and organized physical activities as well screen time were assessed by the parents utilizing a questionnaire. The multiple logistic regression method was used to evaluate the influence of screen time and spontaneous physical activity on various components of physical fitness. Physically active (PA) girls (≥1h/day) and those who participated in additional physical activities (APA) during the week had significantly higher height, weight, and BMI (p<0.001), but not WHtR. They had a higher level of flexibility, explosive strength of the lower limbs and arm strength (p<0.001). With an increase in screen time, the BMI, WHtR increased significantly and explosive strength of the lower limbs, abdominal strength and arm strength were lower. Regression analysis showed that more frequent participation in extracurricular activities increased the values of BMI and WHtR in quartile 4 (Q4), and strength components: Q2–Q4 (p<0.05). Spontaneous physical activity was positively related to the values of BMI, WHtR (both: Q4; p<0.05), explosive force of lower limbs (Q3–Q4; p=0.001), and negatively related to arm strength (Q2; p=0.001). Screen time (≥2hrs/day) increased odds for higher BMI values (p<0.05). Each screen time category decreased the odds of achieving abdominal muscle strength related to the quartiles: Q2–Q4 (p<0.05), arm strength (Q4: p<0.05). ST (1 <2hrs/day) decreased arm strength (Q3; p= 0.045). Our research has shown that screen time-related sedentary behavior and physical activity affect overweight and obesity indices (especially BMI) and strength abilities. The observed associations more often affected girls with a higher level of fitness The results observed in girls aged 6-7 indicate a need for early intervention aimed at limiting time spent watching TV and computer use, as well as to encourage both spontaneous and organized physical activities.

Significance of variation in basal metabolic rate in laboratory mice for translational experiments

The basal metabolic rate (BMR) accounts for 60–70% of the daily energy expenditure (DEE) in sedentary humans and at least 50% of the DEE in laboratory mice in the thermoneutral zone. Surprisingly, however, the significance of the variation in the BMR is largely overlooked in translational research using such indices as physical activity level (PAL), i.e., the ratio of DEE/BMR. In particular, it is unclear whether emulation of human PAL in mouse models should be carried out within or below the thermoneutral zone. It is also unclear whether physical activity within the thermoneutral zone is limited by the capacity to dissipate heat generated by exercise and obligatory metabolic processes contributing to BMR. We measured PAL and spontaneous physical activity (SPA) in laboratory mice from two lines, divergently selected towards either high or low level of BMR, and acclimated to 30 °C (i.e., the thermoneutral zone), 23 or 4 °C. The mean PAL did not differ between both lines in the mice acclimated to 30 °C but became significantly higher in the low BMR mouse line at the lower ambient temperatures. Acclimation to 30 °C reduced the mean locomotor activity but did not affect the significant difference observed between the selected lines. We conclude that carrying out experiments within the thermoneutral zone can increase the consistency of translational studies aimed at the emulation of human energetics, without affecting the variation in physical activity correlated with BMR.

Effects of acute exercise on spontaneous physical activity in mice at different ages

Background Exercise is often used to obtain a negative energy balance. However, its effects on body weight reduction are usually below expectations. One possible explanation is a reduction in spontaneous physical activity (SPA) after exercise since the increase in energy expenditure caused by the exercise session would be offset by the decrease in SPA and its associated energy cost. Thus, we evaluated the effects of a single bout of moderate exercise at individualized intensity on spontaneous physical activity. The impact of the single bout of exercise was determined in early adulthood and at the transition to middle age. Methods Male C57bl/6j (n = 10) mice were evaluated at 4 (4 M) and 9 (9 M) months of age. One week after a treadmill Maximal Exercise Capacity Test (MECT), mice performed a 30-min single bout of exercise at 50 % of the maximal speed reached at MECT. An infrared-based system was used to determine locomotor parameters (SPA and average speed of displacement, ASD) before (basal) and immediately after the single bout of exercise for 48 h (D1, 0-24 h; D2, 24-48 h). Food intake was measured simultaneously. Data were analyzed by GEE and statistical significance was set at p < 0.05. Results Basal SPA declined from 4 M to 9 M (p = 0.01), but maximal exercise capacity was similar. At both ages, SPA and ASD decreased significantly (p < 0.0001) on day 1 after exercise. On D2, SPA returned to basal levels but ASD remained lower than basal (p < 0.001). The magnitude (% of basal) of change in SPA and ASD on D1 and D2 was similar at 4 M and 9 M. Food intake did not change at 4 M but decreased on D2 at 9 M. Conclusions A single bout of moderate exercise decreases physical activity in the first 24 h and average speed of locomotion in the 48 h following exercise. This compensation is similar from early adulthood to the transition to middle age. The decrease in both the amount and intensity (speed) of SPA may compensate for the increase in energy expenditure induced by exercise, helping to understand the below-than-expected effect of exercise interventions to cause a negative energy balance.

Physical Activity and Inhibition of ACE Additively Modulate ACE/ACE-2 Balance in Heart Failure in Mice

Angiotensin-converting enzyme inhibition (ACE-I) and physical activity favorably modulate the ACE/ACE-2 balance. However, it is not clear whether physical activity and ACE-I could synergistically modulate ACE/ACE-2 balance in the course of heart failure (HF). Here, we studied the effects of combined spontaneous physical activity and ACE-I–based treatment on angiotensin (Ang) pattern and cardiac function in a mouse model of HF (Tgαq*44). Tgαq*44 mice with advanced HF (at the age of 12 months) were running spontaneously in a running wheel (exercise training group, ExT) and/or were treated with ACE inhibitor (ACE-I, perindopril, 10 mg/kg) for 2 months. Angiotensin profile was characterized by an LC-MS/MS-based method. The cardiac performance was assessed in vivo by MRI. Ang-(1–7)/Ang II ratio in both plasma and the aorta was significantly higher in the combined treatment group than the ACE-I group or ExT alone, suggesting the additive favorable effects on ACE-2/Ang-(1–7) and ACE/Ang II axes’ balance induced by a combination of ACE-I with ExT. The basal cardiac performance did not differ among the experimental groups of Tgαq*44 mice. We demonstrated additive changes in ACE/ACE-2 balance in both plasma and the aorta by spontaneous physical activity and ACE-I treatment in Tgαq*44 mice. However, these changes did not result in an improvement of failing heart function most likely because the disease was at the end-stage. Ang-(1–7)/Ang II balance represents a valuable biochemical end point for monitoring therapeutic intervention outcome in heart failure.

INTEROCEPTIVE INFORMATION OF PHYSICAL VIGOR: OREXIN NEURONS GAUGE CIRCULATING IGF-I FOR MOTIVATIONAL MOTOR OUTPUT

Brain regulation of bodily functions requires interoceptive feedback signals carrying information about the periphery. As mice with low serum IGF-I levels (LID mice) show reduced spontaneous physical activity, we speculated that body vigor information might be conveyed by circulating IGF-I, a regulator of skeletal muscle and bone mass that enters the brain during physical activity. Since hypothalamic orexin neurons, that are involved in regulating physical activity, express IGF-I receptors (IGF-IR), we hypothesized that these neurons might gauge circulating IGF-I levels. Inactivation of IGF-IR in mouse orexin neurons (Firoc mice) reduced spontaneous activity. Firoc mice maintain normal physical fitness but show anxiety- and depressive-like behaviors that seems to interfere with the rewarding effects of exercise, as they were less sensitive to the rewarding actions of exercise. Further, in response to exercise, Firoc mice showed reduced activation of hypothalamic orexin neurons and ventro-tegmental area (VTA) monoaminergic neurons, as indicated by c-fos staining. Collectively, these results suggest that circulating IGF-I is gauged by orexin neurons to modulate physical activity in part by stimulation of the VTA to motivate motor output. Hence, serum IGF-I may constitute a feedback signal, informing orexin neurons to adapt physical activity to physical vigor.

Inhibition of Orexin/Hypocretin Neurons Ameliorates Elevated Physical Activity and Energy Expenditure in the A53T Mouse Model of Parkinson’s Disease

Aside from the classical motor symptoms, Parkinson’s disease also has various non-classical symptoms. Interestingly, orexin neurons, involved in the regulation of exploratory locomotion, spontaneous physical activity, and energy expenditure, are affected in Parkinson’s. In this study, we hypothesized that Parkinson’s-disease-associated pathology affects orexin neurons and therefore impairs functions they regulate. To test this, we used a transgenic animal model of Parkinson’s, the A53T mouse. We measured body composition, exploratory locomotion, spontaneous physical activity, and energy expenditure. Further, we assessed alpha-synuclein accumulation, inflammation, and astrogliosis. Finally, we hypothesized that chemogenetic inhibition of orexin neurons would ameliorate observed impairments in the A53T mice. We showed that aging in A53T mice was accompanied by reductions in fat mass and increases in exploratory locomotion, spontaneous physical activity, and energy expenditure. We detected the presence of alpha-synuclein accumulations in orexin neurons, increased astrogliosis, and microglial activation. Moreover, loss of inhibitory pre-synaptic terminals and a reduced number of orexin cells were observed in A53T mice. As hypothesized, this chemogenetic intervention mitigated the behavioral disturbances induced by Parkinson’s disease pathology. This study implicates the involvement of orexin in early Parkinson’s-disease-associated impairment of hypothalamic-regulated physiological functions and highlights the importance of orexin neurons in Parkinson’s disease symptomology.

Comparison of physical activity of children in a state kindergarten and a forest kindergarten in the Czech Republic

Introduction: This study compares physical activity of children in a state kindergarten and a forest kindergarten, particularly the number of steps taken, which can indicate the quantity of physical activity. The objective is to monitor the number of steps taken by children in selected institutions and to conduct an analysis in relation to the structure of the daily programme and movement regimen of these institutions contributing thus to the discussion concerning physical literacy formation among preschool children. Methods: The study is of a descriptive non-intervention character using mechanical pedometers. The sample consists of 73 children (36 in the state kindergarten, 37 in the forest kindergarten). The data are processed using a nonparametric Mann-Whitney test and Cohen's d. Results: At the significance level of 0.05 it was discovered that children from the forest kindergarten take significantly more steps in the observed period than children from the state kindergarten. The Z-score is -4.357 and p < 0.001. Substantive significance for the level of physical activity measured by the number of steps is high. Cohen's d = (532057–354714)/133355.005729 = 1.33. Conclusion: Physical literacy is influenced by both the quality of physical activity and the quantity, which was larger in the forest kindergarten. This may be related to the amount of spontaneous physical activity and the frequency and length of trips. However, controlled physical activities in the state kindergarten, especially morning exercise, can improve the quality and increase physical literacy as well. There is a need for a competent approach of teachers, sensitive inclusion of physical activities in the daily programme with emphasis on internal motivation, and awareness of benefits and drawback of both spontaneous physical activity and controlled activities represented by regular morning exercise.

Effects of maternal low-protein diet and spontaneous physical activity on the transcription of neurotrophic factors in the placenta and the brains of mothers and offspring rats

Maternal protein restriction and physical activity can affect the interaction mother–placenta–fetus. This study quantified the gene expression of brain-derived neurotrophic factor (BDNF), neurothrophin 4, tyrosine kinase receptor B (TrkB/NTRK2), insulin-like growth factor (IGF-1), and insulin-like growth factor receptor (IGF-1r) in the different areas of mother’s brain (hypothalamus, hippocampus, and cortex), placenta, and fetus’ brain of rats. Female Wistar rats (n = 20) were housed in cages containing a running wheel for 4 weeks before gestation. According to the distance spontaneously traveled daily, rats were classified as inactive or active. During gestation, on continued access to the running wheel, active and inactive groups were randomized to receive normoprotein diet (18% protein) or a low-protein (LP) diet (8% protein). At day 20 of gestation, gene expression of neurotrophic factors was analyzed by quantitative polymerase chain reaction in different brain areas and the placenta. Dams submitted to a LP diet during gestation showed upregulation of IGF-1r and BDNF messenger RNA in the hypothalamus, IGF-1r and NTRK2 in the hippocampus, and BDNF, NTRK2, IGF-1 and IGF-1r in the cortex. In the placenta, there was a downregulation of IGF-1. In the brain of pups from mothers on LP diet, IGF-1r and NTRK2 were downregulated. Voluntary physical activity attenuated the effects of LP diet on IGF-1r in the hypothalamus, IGF-1r and NTRK2 in the hippocampus, IGF-1 in the placenta, and NTRK2 in the fetus’ brain. In conclusion, both maternal protein restriction and spontaneous physical activity influence the gene expression of BDNF, NTRK2, IGF-1, and IGF-1r, with spontaneous physical activity being able to normalize in part the defects caused by protein restriction during pregnancy.