miRNA is the CREB (cAMP responsive element binding protein) and BDNF (brain-derived neurotrophic factor) signaling pathway, a well known pathway activated by exercise. MicroRNA-132 (miR-132) is a miRNA that is regulated by CREB and is activated by neuronal activity and BDNF. MiR-132 levels are critical for memory development, with very low or high levels having a detrimental effect, and only moderate levels having a positive effect. It has been described that a single bout of acute intermittent exercise rapidly elevated circulating levels of miR-132 in young healthy men. More recently, it has been shown that conditional knockout of miR-132/212 gene cluster impairs memory and promotes gross alterations in hippocampal transcriptional profile in mice. Overall miR-132 is one of the most studied miRNAs in the context of exercise and is proven to be instrumental in multiple functions in the brain, including neuronal development, synaptic plasticity and memory formation. MiR-132 is but one of many miRNAs that are regulated by exercise. Microarray analysis shows a total of 32 miRNAs that are differentially expressed in the hypothalamus when subjected to physical activity. In addition, miR-21 and miR-34a have been shown to be regulated by exercise to reduce the harmful effects of brain injury and aging on cognition. Another miRNA, miR-124, known for its role in neurogenesis and memory formation, is also especially important to attenuate the effects of stress and is unregulated by exercise. Finally, physical exercise leads to altered miR clusters affecting increased cardiac angiogenesis in animal models. MiR-1, miR-133a, and miR-206 cluster levels were significantly elevated after exercise and correlated with performance parameters such as maximum oxygen uptake and anaerobic lactate threshold. Overall, exercise has been shown to alter blood levels of several miRNAs, and this indicates that exercise can use these epigenetic modulators to regulate communication between the brain and peripheral organs. With further knowledge of epigenetic pathways, exercise will continue to show its benefits in all phases of life including but not limited to cancer prevention and treatment, aging, metabolism and metabolic disorders like diabetes and cognition. Implications with obesity While it is easy to state that there is an inverse relationship between physical exercise and obesity, the reality—and scientific evidence—suggest otherwise. To start with a definition, obesity is the excess accumulation of fat within adipose tissue and is characterized by a body mass index (BMI) above 30. Obesity correlates with many cardiometabolic comorbidities such as cancer, cardiovascular conditions