Chapter 1
Chapter 1
One. Multi-omic responses to acute exercise in abdominal subcutaneous adipose tissue of sedentary adults: findings from MoTrPAC
SUMMARY
Exercise induces widespread health benefits across multiple tissues, yet the acute molecular responses in human adipose tissue remain poorly defined. The Molecular Transducers of Physical Activity Consortium profiled temporal molecular changes in abdominal subcutaneous adipose tissue following a single bout of exercise. Healthy sedentary adults were randomized to endurance, resistance, or control groups. Abdominal subcutaneous adipose tissue biopsies were collected pre-exercise and at forty-five minutes, four hours, and twenty-four hours post-exercise, followed by transcriptomic, proteomic, phosphoproteomic, and metabolomic analyses. Endurance and resistance elicited distinct, time-resolved molecular programs involving angiogenesis, extracellular matrix remodeling, mitochondrial metabolism, substrate utilization, and circadian regulation. Phosphoproteomics revealed acute changes in cytoskeletal and branched-chain amino acid metabolism proteins associated with glycemic control. Temporal metabolomic shifts were cell-type-specific. Finally, we identified candidate adipose-derived exerkines with predicted endocrine actions. This multi-omic map of acute abdominal subcutaneous adipose tissue responses offers insight into adipose-specific mechanisms by which exercise promotes metabolic health.
INTRODUCTION
INTRODUCTION
The cardiometabolic health benefits of regular exercise are well-established, yet the molecular mechanisms that drive these effects are incompletely understood. Many of these benefits-such as enhanced whole-body and tissue-specific insulin sensitivity and reduced blood pressure are initiated by single bouts of exercise, even in individuals who exercise regularly. It is widely accepted that the cumulative effects of these repeated, episodic molecular responses to acute exercise bouts underlie the long-term health benefits of training. As such, mapping the molecular landscape of acute exercise responses offers a promising strategy to uncover how exercise promotes cardiometabolic health.
While much of the current and historical focus has been on skeletal muscle and the cardiovascular system, adipose tissue is emerging as a key target of exercise adaptations. Abdominal subcutaneous adipose tissue responds dynamically to both acute exercise and chronic training, contributing to improved cardiometabolic outcomes. Moreover, similar to other tissues, abdominal subcutaneous adipose tissue may also mediate the systemic effects of exercise by serving as a rich source of numerous secreted factors-often referred to as exerkines-that act across tissues. However, the physiological adaptations and molecular-level responses in human abdominal subcutaneous adipose tissue, particularly in the context of temporal and modality-specific dynamics of acute exercise, remains a significant gap.
The Molecular Transducers of Physical Activity Consortium was launched to address this knowledge gap by systematically mapping the molecular effects of physical activity. In this study, which leveraged pre-COVID Molecular Transducers of Physical Activity Consortium human cohort data, we profiled temporal, multi-omic responses in abdominal subcutaneous adipose tissue following a single bout of either endurance exercise or resistance exercise-both of which represent clinically relevant exercise prescriptions at an unprecedented scale. Here, we reveal temporal-, modality-, and cell-type-specific molecular responses in the abdominal subcutaneous adipose tissue transcriptome, proteome, phosphoproteome, and metabolome following acute exercise. We examine the clinical relevance of these molecular signatures and, through in silico modeling, explore the potential endocrine role of abdominal subcutaneous adipose tissue-derived exerkines. Together, our findings provide new insights into the mechanisms underlying early abdominal subcutaneous adipose tissue-specific molecular responses to exercise and identify candidate mediators of long-term metabolic benefits.