Is reduction in appetite beneficial for body weight management in the context of overweight and obesity? Yes, according to the SATIN (Satiety Innovation) study

New dietary-based concepts are needed for treatment and effective prevention of overweight and obesity. The primary objective was to investigate if reduction in appetite is associated with improved weight loss maintenance. This cohort study was nested within the European Commission project Satiety Innovation (SATIN). Participants achieving ≥8% weight loss during an initial 8-week low-energy formula diet were included in a 12-week randomised double-blind parallel weight loss maintenance intervention. The intervention included food products designed to reduce appetite or matching controls along with instructions to follow national dietary guidelines. Appetite was assessed by ad libitum energy intake and self-reported appetite evaluations using visual analogue scales during standardised appetite probe days. These were evaluated at the first day of the maintenance period compared with baseline (acute effects after a single exposure of intervention products) and post-maintenance compared with baseline (sustained effects after repeated exposures of intervention products) regardless of randomisation. A total of 181 participants (forty-seven men and 134 women) completed the study. Sustained reduction in 24-h energy intake was associated with improved weight loss maintenance (R 0·37; P = 0·001), whereas the association was not found acutely (P = 0·91). Suppression in self-reported appetite was associated with improved weight loss maintenance both acutely (R −0·32; P = 0·033) and sustained (R −0·33; P = 0·042). Reduction in appetite seems to be associated with improved body weight management, making appetite-reducing food products an interesting strategy for dietary-based concepts

Genetic predisposition to adiposity is associated with increased objectively assessed sedentary time in young children.

Increased sedentariness has been linked to the growing prevalence of obesity in children, but some longitudinal studies suggest that sedentariness may be a consequence rather than a cause of increased adiposity. We used Mendelian randomization to examine the causal relations between body mass index (BMI) and objectively assessed sedentary time and physical activity in 3-8 year-old children from one Finnish and two Danish cohorts [NTOTAL=679]. A genetic risk score (GRS) comprised of 15 independent genetic variants associated with childhood BMI was used as the instrumental variable to test causal effects of BMI on sedentary time, total physical activity, and moderate-to-vigorous physical activity (MVPA). In fixed effects meta-analyses, the GRS was associated with 0.05 SD/allele increase in sedentary time (P=0.019), but there was no significant association with total physical activity (beta=0.011 SD/allele, P=0.58) or MVPA (beta=0.001 SD/allele, P=0.96), adjusting for age, sex, monitor wear-time and first three genome-wide principal components. In two-stage least squares regression analyses, each genetically instrumented one unit increase in BMI z-score increased sedentary time by 0.47 SD (P=0.072). Childhood BMI may have a causal influence on sedentary time but not on total physical activity or MVPA in young children. Our results provide important insights into the regulation of movement behaviour in childhood

Measuring perceived exercise capability and investigating its relationship with childhood obesity: a feasibility study.

BACKGROUND/OBJECTIVES: According to the COM-B ('Capability', 'Opportunity', 'Motivation' and 'Behaviour') model of behaviour, three factors are essential for behaviour to occur: capability, opportunity and motivation. Obese children are less likely to feel capable of exercising. The implementation of a new methodological approach to investigate the relationship between perceived exercise capability (PEC) and childhood obesity was conducted, which involved creating a new instrument, and demonstrating how it can be used to measure obesity intervention outcomes. SUBJECTS/METHODS: A questionnaire aiming to measure perceived exercise capability, opportunity and motivation was systematically constructed using the COM-B model and administered to 71 obese children (aged 9-17 years (12.24±0.2.01), body mass index (BMI) standard deviation scores (SDS) 2.80±0.660) at a weight-management camp in northern England. Scale validity and reliability was assessed. Relationships between PEC, as measured by the questionnaire, and BMI SDS were investigated for the children at the weight-management camp, and for 45 Spanish schoolchildren (aged 9-13 years, (10.52±1.23), BMI SDS 0.80±0.99). A pilot study, demonstrating how the questionnaire can be used to measure the effectiveness of an intervention aiming to bring about improved PEC for weight-management camp attendees, was conducted. No participants withdrew from these studies. RESULTS: The questionnaire domain (exercise capability, opportunity and motivation) composite scales were found to have adequate internal consistency (a=0.712-0.796) and construct validity (χ(2)/degrees of freedom=1.55, root mean square error of approximation=0.072, comparative fit index=0.92). Linear regression revealed that low PEC was associated with higher baseline BMI SDS for both UK (b=-0.289, P=0.010) and Spanish (b=-0.446, P=0.047) participants. Pilot study findings provide preliminary evidence for PEC improvements through intervention being achievable, and measurable using the questionnaire. CONCLUSIONS: Evidence is presented for reliability and validity of the questionnaire, and for feasibility of its use in the context of a childhood obesity intervention. Future research could investigate the link between PEC and childhood obesity further

Seasonal variation in objectively measured physical activity, sedentary time, cardio-respiratory fitness and sleep duration among 8–11 year-old Danish children: a repeated-measures study

Abstract Background Understanding fluctuations in lifestyle indicators is important to identify relevant time periods to intervene in order to promote a healthy lifestyle; however, objective assessment of multiple lifestyle indicators has never been done using a repeated-measures design. The primary aim was, therefore, to examine between-season and within-week variation in physical activity, sedentary behaviour, cardio-respiratory fitness and sleep duration among 8–11 year-old children. Methods A total of 1021 children from nine Danish schools were invited to participate and 834 accepted. Due to missing data, 730 children were included in the current analytical sample. An accelerometer was worn for 7 days and 8 nights during autumn, winter and spring, from which physical activity, sedentary time and sleep duration were measured. Cardio-respiratory fitness was assessed using a 10-min intermittent running test. Results The children had 5% more sedentary time, 23% less time in moderate-to-vigorous physical activity and 2% longer sleep duration during winter compared to spring and cardio-respiratory fitness was 4% higher during spring compared to autumn (P < 0.001). Sedentary time was higher and total physical activity, moderate-to-vigorous physical activity and sleep duration (boys only) were lower during weekends at all seasons (P ≤ 0.01). Intraclass correlation coefficients between seasons ranged from 0.47-0.74, leaving 45-78% to seasonal variation. Conclusions Overall, sedentary time was higher and physical activity lower during winter and during weekends. The most accurate and unbiased estimates of physical activity came from autumn; however, the considerable intra-individual variation suggests that a single measurement may not adequately characterise children’s habitual sleep and activity

A school-based physical activity promotion intervention in children: rationale and study protocol for the PREVIENE Project

The lack of physical activity and increasing time spent in sedentary behaviours during childhood place importance on developing low cost, easy-toimplement school-based interventions to increase physical activity among children. The PREVIENE Project will evaluate the effectiveness of five innovative, simple, and feasible interventions (active commuting to/from school, active Physical Education lessons, active school recess, sleep health promotion, and an integrated program incorporating all 4 interventions) to improve physical activity, fitness, anthropometry, sleep health, academic achievement, and health-related quality of life in primary school children. The PREVIENE Project will provide the information about the effectiveness and implementation of different school-based interventions for physical activity promotion in primary school children.The PREVIENE Project was funded by the Spanish Ministry of Economy and Competitiveness (DEP2015-63988-R, MINECO-FEDER). MAG is supported by grants from the Spanish Ministry of Economy and Competitivenes

Nicotinic receptors

Regulation of normal or abnormal behaviour is critically controlled by the central serotonergic systems. Recent evidence has suggested that serotonin (5-HT) neurotransmission dysfunction contributes to a variety of pathological conditions, including depression, anxiety, schizophrenia and Parkinson’s disorders. There is also a great amount of evidence indicating that 5-HT signalling may affect the reinforcing properties of drugs of abuse by the interaction and modulation of dopamine (DA) function. This chapter is focused on one of the more addictive drugs, nicotine. It is widely recognised that the effects of nicotine are strongly associated with the stimulatory action it exhibits on mesolimbic DAergic function. We outline the role of 5-HT and its plethora of receptors, focusing on 5-HT2 subtypes with relation to their involvement in the neurobiology of nicotine addiction. We also explore the novel pharmacological approaches using 5-HT agents for the treatment of nicotine dependence. Compelling evidence shows that 5-HT2C receptor agonists may be possible therapeutic targets for smoking cessation, although further investigation is required.peer-reviewe

A short history of the 5-HT2C receptor: from the choroid plexus to depression, obesity and addiction treatment

This paper is a personal account on the discovery and characterization of the 5-HT2C receptor (first known as the 5- HT1C receptor) over 30 years ago and how it translated into a number of unsuspected features for a G protein-coupled receptor (GPCR) and a diversity of clinical applications. The 5-HT2C receptor is one of the most intriguing members of the GPCR superfamily. Initially referred to as 5-HT1CR, the 5-HT2CR was discovered while studying the pharmacological features and the distribution of [3H]mesulergine-labelled sites, primarily in the brain using radioligand binding and slice autoradiography. Mesulergine (SDZ CU-085), was, at the time, best defined as a ligand with serotonergic and dopaminergic properties. Autoradiographic studies showed remarkably strong [3H]mesulergine-labelling to the rat choroid plexus. [3H]mesulergine-labelled sites had pharmacological properties different from, at the time, known or purported 5-HT receptors. In spite of similarities with 5-HT2 binding, the new binding site was called 5-HT1C because of its very high affinity for 5-HT itself. Within the following 10 years, the 5-HT1CR (later named 5- HT2C) was extensively characterised pharmacologically, anatomically and functionally: it was one of the first 5-HT receptors to be sequenced and cloned. The 5-HT2CR is a GPCR, with a very complex gene structure. It constitutes a rarity in theGPCR family: many 5-HT2CR variants exist, especially in humans, due to RNA editing, in addition to a few 5-HT2CR splice variants. Intense research led to therapeutically active 5-HT2C receptor ligands, both antagonists (or inverse agonists) and agonists: keeping in mind that a number of antidepressants and antipsychotics are 5- HT2CR antagonists/inverse agonists. Agomelatine, a 5-HT2CR antagonist is registered for the treatment of major depression. The agonist Lorcaserin is registered for the treatment of aspects of obesity and has further potential in addiction, especially nicotine/ smoking. There is good evidence that the 5-HT2CR is involved in spinal cord injury-induced spasms of the lower limbs, which can be treated with 5-HT2CR antagonists/inverse agonists such as cyproheptadine or SB206553. The 5-HT2CR may play a role in schizophrenia and epilepsy. Vabicaserin, a 5-HT2CR agonist has been in development for the treatment of schizophrenia and obesity, but was stopped. As is common, there is potential for further indications for 5-HT2CR ligands, as suggested by a number of preclinical and/or genome-wide association studies (GWAS) on depression, suicide, sexual dysfunction, addictions and obesity. The 5-HT2CR is clearly affected by a number of established antidepressants/antipsychotics and may be one of the culprits in antipsychotic-induced weight gain

Birth weight, cardiometabolic risk factors and effect modification of physical activity in children and adolescents: pooled data from 12 international studies

Abstract: Objectives: Low and high birth weight is associated with higher levels of cardiometabolic risk factors and adiposity in children and adolescents, and increases the risk of cardiovascular diseases, obesity, and early mortality later in life. Moderate-to-vigorous physical activity (MVPA) is associated with lower cardiometabolic risk factors and may mitigate the detrimental consequences of high or low birth weight. Thus, we examined whether MVPA modified the associations between birth weight and cardiometabolic risk factors in children and adolescents. Methods: We used pooled individual data from 12 cohort- or cross-sectional studies including 9,100 children and adolescents. Birth weight was measured at birth or maternally reported retrospectively. Device-measured physical activity (PA) and cardiometabolic risk factors were measured in childhood or adolescence. We tested for associations between birth weight, MVPA, and cardiometabolic risk factors using multilevel linear regression, including study as a random factor. We tested for interaction between birth weight and MVPA by introducing the interaction term in the models (birth weight x MVPA). Results: Most of the associations between birth weight (kg) and cardiometabolic risk factors were not modified by MVPA (min/day), except between birth weight and waist circumference (cm) in children (p = 0.005) and HDL-cholesterol (mmol/l) in adolescents (p = 0.040). Sensitivity analyses suggested that some of the associations were modified by VPA, i.e., the associations between birth weight and diastolic blood pressure (mmHg) in children (p = 0.009) and LDL- cholesterol (mmol/l) (p = 0.009) and triglycerides (mmol/l) in adolescents (p = 0.028). Conclusion: MVPA appears not to consistently modify the associations between low birth weight and cardiometabolic risk. In contrast, MVPA may mitigate the association between higher birth weight and higher waist circumference in children. MVPA is consistently associated with a lower cardiometabolic risk across the birth weight spectrum. Optimal prenatal growth and subsequent PA are both important in relation to cardiometabolic health in children and adolescents