Decoding endocrine and paracrine communication through mammokines

Project Summary Interactions among different organs are pivotal in developing pathological conditions like obesity and type 2 diabetes. Substantial research efforts have been directed towards comprehending how communication between cell types such as adipocytes, hepatocytes, and islets contribute to and respond to specific disruptions associated with metabolic diseases. There remains an essential yet relatively unexplored question: how does the secretome of the mammary gland's luminal epithelium influence inter-organ communication in the context of obesity? Breastfeeding holds a significant role in promoting the health of mothers and reducing the risk of diabetes, benefiting both maternal and neonatal health. It also protects against cardiovascular diseases, obesity, and other metabolic disorders for both the mother and child. However, obesity can disrupt mammary gland function and development, potentially affecting maternal well-being and the health of offspring. Recent technological advancements, such as single-cell transcriptomics and precision proteomics, have opened up opportunities for unbiased exploration and the discovery of signaling molecules involved in inter-organ communication. We recently employed a bioinformatics framework based on single-cell transcriptomic correlations, integrating data from multiple datasets with publicly available resources to identify secretory factors from mammary duct luminal cells that influence surrounding adipocyte metabolism. We refer to these factors as "mammokines." Our innovative research endeavor seeks to combine transcriptomics and proteomics to unveil the ambiguities surrounding the mammary gland's function as an endocrine organ and the impact of obesity on its action. The primary goal of this project is to discover new mammokines that may have vital roles in paracrine and endocrine signaling, influencing the function and homeostasis of the liver, pancreas, adipose tissue, and the mammary gland itself, potentially affecting the progression of obesity and Type 2 diabetes phenotypes. These mammokines could serve as valuable biomarkers for obesity and diabetes in women. We also aim to determine which pathways are conserved from mice to humans and investigate the physiological consequences of disrupted endocrine communication through functional experiments. The success of these objectives relies on integrating transcriptomics, proteomics, computational, and experimental approaches, which is supported by the extensive training and expertise of the Principal Investigator and collaborators. We believe this research has great potential to advance our understanding of women's metabolic health and inspire innovative strategies for obesity and diabetes therapy.