Endocrine Abstracts

Fat distribution influences metabolic risk. Accumulation of fat in the upper body increases metabolic risk, while lower body adipose expansion is protective. Oestrogen promotes lower body adiposity; transgender women on oestrogen therapy show increases in gluteal adipose, while transition to the menopause is associated with a shift in fat distribution towards the upper body, concurrent with changes in metabolic risk. Still, mechanisms governing the depot-specific effects of oestrogen on fat distribution are poorly understood but likely to involve cell-to-cell communication between preadipocytes and resident immune cells. To investigate crosstalk between adipose tissue cell types, we have explored single cell RNA sequencing data taken from paired abdominal and gluteal adipose biopsies from healthy male and female subjects. By running a differential gene expression analysis paired with an interactome analysis, we have identified a limited number of depot- and gender-specific ligand receptor interactions between preadipocytes and macrophages. To test the functional significance of ligand-receptor pairs we are performing in vitro co-culture studies using depot-specific human preadipocyte cell lines together with human monocytes. The lead ligand candidate is an oestrogen-inducible peptide secreted by preadipocytes, subsequently conveying an anti-inflammatory response in resident macrophages. The detailed knowledge of this signalling system will provide opportunities for novel therapeutics for metabolic disorders.