Chapter 1
Chapter 1
Blood Biochemical Responses to Acute Exercise: Findings from the Molecular Transducers of Physical Activity Consortium
Abstract: Exercise benefits numerous organ systems and tissues, however limited knowledge exists about its underlying molecular pathways. Identifying the exercise-induced biochemical changes that occur in the circulation may provide further insights into how exercise confers systemic health changes. Here, we perform large-scale plasma proteomic, metabolomic, and whole blood transcriptional profiling in sedentary human participants undergoing acute endurance exercise, resistance exercise, or a non-exercise control in up to seven timepoints over a twenty-four hour period. We observe six thousand sixty-six transcript, one hundred eighty-nine protein, and four hundred forty-eight metabolite changes in response to endurance exercise or resistance exercise compared to non-exercise control. Our analyses reveal numerous shared biochemical responses between endurance exercise and resistance exercise modes, but also differences in immune cell responses, lipid metabolism, and pathways reflective of tissue repair and angiogenesis. Taken together, our findings highlight novel temporal and exercise mode-specific blood-based molecular responses to acute exercise, and provide a new resource for the scientific community.
Introduction:
Introduction:
Exercise's health benefits are uniquely expansive, leading to improvements in cardiorespiratory fitness and metabolism, muscle strength, mood and cognition, healthy aging, and a lower risk of chronic diseases including cancer, obesity, diabetes and cardiovascular disease. It is unsurprising then, that exercise is among the most robust physiologic stimuli, affecting a network of cellular processes and organ systems spanning the cardiovascular, pulmonary, musculoskeletal, neurologic, and endocrine systems among others. While exercise is widely regarded as beneficial, its effects are heterogeneous and vary according to both its exposure (i.e., mode and duration of exercise) as well as host factors such as age, training background, nutritional status, and the presence or absence of underlying pathologic conditions.
Furthermore, there is increasing recognition that genetic and genomic heterogeneity play a role in inter-individual differences in the response to exercise. Despite this, our understanding of the biochemical pathways that underlie the physiologic effects of exercise and exercise-response traits is incomplete, providing strong rationale to investigate its molecular transducers, a principal goal of the Molecular Transducers of Physical Activity Consortium.
The blood as a "highway" of whole-body physiology is particularly relevant to the study of how exercise mediates its systemic effects through inter-organ cross-talk. Indeed, exercise induces widespread molecular changes even in tissues not directly involved in locomotor activity. These concepts are underscored by the emerging paradigm of "exerkines", or exercise-stimulated soluble biochemicals that can act in autocrine, paracrine, or endocrine fashion to confer exercise's health benefits. A growing list of small molecule metabolites, lipids, peptides and nucleic acids in the plasma have been identified as candidate exerkines, yet even among these known biochemicals there is limited knowledge about their temporal changes during acute exercise, their responses to distinct exercise modes, and their tissue source(s). While the exerkine paradigm reflects beneficial actors, exercise can also improve health through the downregulation or increased clearance of deleterious, circulating factors - an understudied area of investigation. In addition to its application in studying exercise's integrative physiology, molecular profiling in the blood offers a practical means to identify biochemical signatures of a health or disease state. Prior works have shown that blood-based signatures can identify differential health responses to an exercise intervention, reflect cardiorespiratory fitness, and that these signatures may in turn predict long-term human health outcomes. Prior studies leveraging blood biochemical profiling have used either a lone molecular profiling method, focused on either a select group of analytes, a single time point and/or an individual exercise mode, or have lacked a non-exercise control arm, motivating a more comprehensive, multi-omic examination of blood in response to exercise that leverages a control group.
Here, we describe large-scale whole-blood transcriptomic, plasma proteomic and metabolomic profiling in well-phenotyped sedentary adults from the Molecular Transducers of Physical Activity Consortium study to characterize the multi-omic responses to acute exercise in the circulation. We compare and contrast biochemical responses to bouts of endurance exercise and resistance exercise at up to seven different time points over the course of twenty-four hours using a non-exercise control group to rigorously isolate the effects of exercise from those driven by time of day, fasting, and biospecimen collection. We further integrate the biochemical responses across the three profiling techniques and relate blood-based biochemical features across a range of cardiorespiratory, muscle strength and metabolic phenotypes assessed in Molecular Transducers of Physical Activity Consortium.