Obesity disrupts innate-adaptive immune network patterning in adipose tissue

Obesity drives significant changes in adipose tissue that precede development of tissue and systemic insulin resistance. Immune cell infiltration and inflammation are known contributors to these changes but there is limited understanding of their spatial context tissue-wide. We sought to identify spatial patterning in epididymal adipose tissue immune cells in a time course of diet-induced obesity in mice. Using spatial transcriptomics and single-cell RNA-sequencing, we identified dominant cell type signatures preserved in their anatomical context, quantified gene expression patterns at spots throughout adipose tissue, performed cell type network analysis, and investigated ligand-receptor colocalization. Our data support increased innate immune cells, including macrophages, monocytes, and innate lymphoid cells, with tissue-wide interspersion and dampened adaptive immune cell signatures with obesity. Network analysis identified increased heterogeneity in all major immune cell types, consistent with increased subtypes. To capture tissue dynamics at obesity onset, we draw on mathematical principles from linear algebra and spectral graph theory. We provide a framework for better understanding cell cooperation toward emergence of multicellular tissue function. Further, we adapt Turing's mathematical theory on morphogenesis to show lapse of emergence in adipose tissue. Paired spatial transcriptomics and single-cell RNA-sequencing data collected from contralateral epididymal white adipose tissue in mice fed a normal chow diet (0-weeks) or a high-fat diet for 8-weeks or 14-weeks. The normal diet spatial transcriptomics sample contains two replicates. ***Please note that the GSM5935796-GSM5935798 sample records have been updated with visium imaging and scale factors data on Aug 5, 2024****