Adipose tissue and adipose secretome in systemic sclerosis

Adipose tissue is closely associated with systemic sclerosis (SSc)-pathology, both anatomically and functionally. This review focuses on local effects of adipocytes in the context of adipose to mesenchymal transdifferentiation (AMT), effects of the adipose stromal vascular fraction on SSc pathogenesis and systemic effects of adipose tissue secretome.Novel populations of fibroblasts evolving from adipose tissue were identified- for example COL11+ cancer-associated fibroblasts differentiated from adipose-derived stromal cells. Lipofibroblasts in human lungs were described using nonconventional markers that allow more effective population identification. These findings could make an important contribution to further clarification of adipocyte involvement in SSc.Recent studies confirmed that lipolysis contributes to fibrogenesis through AMT differentiation and release of fatty acids (FA). Unbalanced metabolism of FA has been reported in several studies in SSc. Other adipose tissue secretome molecules (e.g. lysophosphatidic acid), novel adipokines and extracellular vesicles from adipose mesenchymal stem cells make important contributions to the pro-/antifibrotic balance.There is a growing evidence of important contribution of adipose tissue and its secretome to SSc pathogenesis. Novel techniques such as single-cell RNA sequencing (scRNAseq) and metabolomics, albeit challenging to use in adipose tissue, will provide further evidence.