Project description:We studied the opposing effects of exercise training and high-fat diet at single-cell resolution to reveal changes in cell type abundance, cell-type-specific gene expression/pathway/regulatory network changes, and changes in cell-cell communication both within and across tissues. We profiled scRNA-seq in 204,883 cells, grouped into 53 distinct cell sub-types/states across 22 major cell types, from subcutaneous white adipose tissue, visceral white adipose tissue, and skeletal muscle across 16 lean and 15 obese mice with both diet and exercise interventions. Changes in both cell proportion and transcriptional state were most strongly pronounced in adipose stem cells in fat, consistent with roles of adipogenesis in thermogenesis-vs-lipogenesis and hyperplasia-vs-hypertrophy in obesity. For immune cells, exercise training decreases obesity-associated inflammatory tissue-resident cell populations, including myeloid and regulatory T cells, and promotes beige-cell-inducing populations, including NKT cells. These changes clustered in common pathways across tissues for both exercise and obesity, including extracellular matrix remodelling and circadian rhythm in mesenchymal stem cells and cell activation/migration in immune cells.
Project description:We studied the opposing effects of exercise training and high-fat diet at tissue-level resolution to reveal gene expression and pathway changes in subcutaneous white adipose tissue, visceral white adipose tissue, and skeletal muscle. We revealed gene modules consistently up-regulated by exercise training, which include fatty acid biosynthesis/beta-oxidation/metabolism, oxidative phosphorylation, TCA cycle, and ROS response. Modules down-regulated by exercise training in all three tissues are antigen presentation, neutrophil degranulation, immune cell migration, phagosome-related genes, ECM-related genes, proliferation, and ribonucleotide biosynthesis. Taken together, exercise training improves fatty acid metabolism and cellular respiration similarly across the three metabolic tissues, and represses immune, ECM, proliferation and tissue-specific pathways.
Project description:Exercise training is critical for the prevention and treatment of obesity, but its underlying mechanisms remain incompletely understood given the challenge of profiling heterogeneous effects across multiple tissues and cell types. Here, we address this challenge and opposing effects of exercise and high-fat diet (HFD)-induced obesity at single-cell resolution in subcutaneous and visceral white adipose tissue and skeletal muscle in mice with diet and exercise training interventions. We identify a prominent role of mesenchymal stem cells (MSCs) in obesity and exercise-induced tissue adaptation. Among the pathways regulated by exercise and HFD in MSCs across the three tissues, extracellular matrix remodeling and circadian rhythm are the most prominent. Inferred cell-cell interactions implicate within- and multi-tissue crosstalk centered around MSCs. Overall, our work reveals the intricacies and diversity of multi-tissue molecular responses to exercise and obesity and uncovers a previously underappreciated role of MSCs in tissue-specific and multi-tissue beneficial effects of exercise.
