physical activity

Metabolic Assessment of Metformin in Pregnancy (MoM-P)

PROJECT SUMMARY The objective of the “Metabolic Assessment of Metformin in Pregnancy “(MoM-P) proposal is to assess the physiological effect of metformin on maternal and neonatal metabolism during pregnancy in individuals developing gestational diabetes (GDM). Metformin is increasingly being used for medical treatment of GDM not adequately treated with nutrition and physical activity. There is inconsistency among various organizations (Society for Maternal Fetal Medicine, American College of Obstetrics and Gynecology and the American Diabetes Association) as to metformin’s role in the medical management of GDM. We will examine the metabolic action of metformin in GDM pregnancies and effect on mothers and their offspring. We plan to recruit 50 participants from Massachusetts General Hospital (MGH) for Specific Aims 1, 2 and 3 and 100 participants from Ohio State University college of Medicine (OSUCOM) for Specific Aims 2 and 3. Participants for the study will have been diagnosed with GDM requiring medical management of GDM as part of the DECIDE multicenter randomized controlled trial. The primary site for DECIDE is OSUCOM, with Dr. Mark Landon as the PI. The MoM-P study will recruit participants from the DECIDE trial at MGH and OSUCOM. The MoM-P study aims are: Aim 1: To establish metformin’s effects on endogenous (primarily hepatic) glucose production (EGP) and insulin sensitivity in late pregnancy. We hypothesize that metformin does not lower EGP in pregnancy and hence the need of additional insulin in the medical management of GDM. We will perform infusion of a stable isotope of glucose (6,6 2H2 glucose) to estimate EGP and a HOMA-IR prior to initiation of medical management and again at 37 weeks gestation. Aim 2: Metformin increases GDF15 levels in human GDM pregnancy and is associated with lower nutrient intake, gestational weight gain (GWG) and increased resting energy expenditure (REE). We hypothesize that metformin increases GDF15 concentrations which lead to GI upset, lower caloric intake/GWG and increases REE. In DECIDE participants randomized to metformin vs. insulin, we will measure GDF15 and examine the relationship to ASA-nutrition records, REE with indirect calorimetry and maternal body composition using air displacement plethysmography (ADP) prior to initiation of medication and again at 37 weeks. Aim 3: To compare fetal growth and body composition in neonates exposed and unexposed to metformin in utero. We hypothesize that metformin treatment of GDM decreases fetal weight: 1) directly based on metformin’s effect on neonatal metabolism (fetal AMPK and mTOR pathways) and 2) indirectly by lowering maternal nutritional intake, fat free mass (FFM) and increasing maternal REE, resulting in decreased neonatal FFM and increased fat mass in childhood. In DECIDE participants, we will measure neonatal body composition with 72 hours of delivery using pediatric ADP and a planned follow-up of children at 2 years in the DECIDE protocol with estimates of male and female children’s body composition.

Post-diagnosis changes in body composition and renal cell cancer survival

ABSTRACT Significance. Clear cell renal cell carcinoma (ccRCC) is the most common form of kidney cancer and most lethal subtype, and there is great interest in the identification of potentially modifiable prognostic factors. Although weight status seems to be relevant, the relationship between body mass index (BMI) at diagnosis and survival among ccRCC patients indicates that mortality is lowest among those classified as overweight or obese at the time of diagnosis by BMI. This has resulted in confusion in clinical guidance for weight management among ccRCC patients. Recent work involving body composition features (adipose and muscle tissue) has provided some insight, but we do not understand how weight or body composition changes after diagnosis relate to survival, nor how these changes relate to pathological and molecular tumor features— information which is needed to resolve this controversy. Rigorous analytical approaches are further required to accurately address these questions. Innovation. Our study is highly innovative in that 1) we will be the first to leverage a large-scale cohort of ccRCC patients with multiple assessments of weight and body composition from diagnosis onward; 2) we will examine tumor characteristics, including molecular features, as potential drivers of these changes; and 3) we will use a rigorous joint modeling approach to simultaneously model the post-diagnosis trajectories of weight and body composition and their relationships with cancer outcomes in the most statistically sound manner. Our findings will inform clinical management of, and identify modifiable body composition features to improve survival for the growing number of ccRCC patients. Approach. We will use available data from the RESOLVE cohort, an NCI-funded retrospective cohort of 1,239 Stage I-III clear-cell renal cell carcinoma (ccRCC) patients diagnosed between 2000-2020 at Memorial Sloan Kettering Cancer Center. These data include clinical and patient-level factors collected from the medical record, including repeated height and weight assessments, body composition measures from existing computed tomography scans, pathological and molecular tumor characteristics, and overall survival (OS) and disease-free survival (DFS). We will use a joint modeling approach to simultaneously model changes in post-diagnosis body weight (Aim 1) and OS and DFS, as well as post-diagnosis changes in muscle and adipose tissue features (Aim 2) and OS and DFS. Models will include molecular tumor characteristics as predictors of these longitudinal trajectories. Impact. These results will provide crucial insight into the relationship between body composition changes and outcomes among ccRCC patients, and potentially identify tumor-related characteristics driving these associations. These results will resolve apparent paradoxes around the relationship between obesity and ccRCC mortality and identify potential targets for nutrition and physical activity interventions on body composition.

Physical Activity, Sedentary Behaviour and Brain Health

Uncovering the molecular effectors of diet and exercise

Despite the profound effects of nutrition and physical activity on human health, our understanding of the molecules mediating the salutary effects of specific foods or activities remains remarkably limited. Here, we share our ongoing studies that use unbiased and high-resolution metabolomics technologies to uncover the molecules and molecular effectors of diet and exercise. We describe how exercise stimulates the production of Lac-Phe, a blood-borne signaling metabolite that suppresses feeding and obesity. Ablation of Lac-Phe biosynthesis in mice increases food intake and obesity after exercise. We also describe the discovery of an orphan metabolite, BHB-Phe. Ketosis-inducible BHB-Phe is a congener of exercise-inducible Lac-Phe, produced in CNDP2+ cells when levels of BHB are high, and functions to lower body weight and adiposity in ketosis. Our data uncover an unexpected and underappreciated signaling role for metabolic fuel derivatives in mediating the cardiometabolic benefits of diet and exercise. These data also suggest that diet and exercise may mediate their physiologic effects on energy balance via a common family of molecules and overlapping signaling pathways.

The neuroscience of lifestyle interventions for mental health: the BrainPark approach

Our everyday behaviours, such as physical activity, sleep, diet, meditation, and social connections, have a potent impact on our mental health and the health of our brain. BrainPark is working to harness this power by developing lifestyle-based interventions for mental health and investigating how they do and don’t change the brain, and for whom they are most effective. In this webinar, Dr Rebecca Segrave and Dr Chao Suo will discuss BrainPark’s approach to developing lifestyle-based interventions to help people get better control of compulsive behaviours, and the multi-modality neuroimaging approaches they take to investigating outcomes. The webinar will explore two current BrainPark trials: 1. Conquering Compulsions - investigating the capacity of physical exercise and meditation to alter reward processing and help people get better control of a wide range of unhelpful habits, from drinking to eating to cleaning. 2. The Brain Exercise Addiction Trial (BEAT) - an NHMRC funded investigation into the capacity of physical exercise to reverse the brain harms caused by long-term heavy cannabis use. Dr Rebecca Segrave is Deputy Director and Head of Interventions Research at BrainPark, the David Winston Turner Senior Research Fellow within the Turner Institute for Brain and Mental Health, and an AHRPA registered Clinical Neuropsychologist. Dr Chao Suo is Head of Technology and Neuroimaging at BrainPark and a Research Fellow within the Turner Institute for Brain and Mental Health.

Two endophenotypes of anorexia nervosa based on clinical factors related to physical activity and leptin levels

Enhancing dendritic spine plasticity by coupling physical activity with non-invasive brain stimulation

Physical activity adapts the BDNF/TrkB signalling towards a molecular fatigue-resistant phenotype at the NMJ

Physical activity - is it invariably beneficial?

Physical activity protects from hypothalamic neuroinflammation in a chronic food restriction mouse model

The threshold of beneficial effect of regular physical activity on behavioral deficits in animal model of Parkinson’s disease

Beneficial role of physical activity in counteracting musculoskeletal disorders induced by early movement restriction

FENS Forum 2024

GABAA receptors modulate anxiety-like behavior through the central amygdala area in rats with higher physical activity

FENS Forum 2024

Can physical activity boost vocabulary learning?

FENS Forum 2024

Physical activity sensitizes vagal gut-brain communication underlying feeding control

FENS Forum 2024

The role of lifetime physical activity on Parkinson’s symptoms severity - Revenge of the couch potato?

FENS Forum 2024