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.

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.