The early transition to cold-induced browning in mouse subcutaneous white adipose tissue (scWAT) involves proteins related to nerve remodeling, cytoskeleton, mitochondria, and immune cells

Abstract

White adipose tissue (WAT) is a dynamic organ capable of remodelling in response to metabolic state. For example, in response to stimuli such as cold exposure, WAT can develop inducible brown adipocytes (‘browning’) capable of non-shivering thermogenesis, through concurrent changes to mitochondrial content and function. This is aided by increased neurite outgrowth and angiogenesis across the tissue, providing the needed neurovascular supply for uncoupling protein 1 activation. While several RNA-sequencing studies have been performed in WAT, including newer single cell and single nuclei studies, little work has been done to investigate changes to the adipose proteome, particularly during dynamic periods of tissue remodelling such as cold stimulation. Here, we conducted a comprehensive proteomic analysis of inguinal subcutaneous (sc) WAT during the initial ‘browning’ period of 24 or 72hrs of cold exposure in mice. We identified four significant pathways impacted by cold stimulation that are involved in tissue remodelling, which included mitochondrial function and metabolism, cytoskeletal remodelling, the immune response, and the nervous system. Taken together, we found that early changes in the proteome of WAT with cold stimulation predicted later structural and functional changes in the tissue that are important for tissue and whole-body remodelling to meet energetic and metabolic needs.

Keywords

• Adipose immune cell recruitment and activation
• adipose remodelling
• adipose tissue innervation
• Mitochondria
• Adipsoe proteomics