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"... In a new study, Yale researchers have started to uncover what happens at the cellular and molecular levels as skin fibrosis progresses, and the findings, they say, yield potential targets for treating fibrotic diseases in the future. ...
When the researchers stopped fibrosis stimulation, they saw that the adipocytes refilled with lipids as the skin began to recover. ..."
the researchers found that adipocyte depletion happens quite early in the fibrotic process.
Adipocytes in the skin contain one large liquid droplet of fat molecules (or lipids), which can be released from the cell in response to various biological events. In the two mouse models of skin fibrosis used in the new study, the researchers observed that adipocytes in the area where fibrosis was stimulated lost their lipid droplets as early as five days into fibrosis development.
From the abstract:
"During skin fibrosis, extracellular matrix (ECM) proteins are overproduced, and resident lipid-filled, mature dermal adipocytes are depleted in both human disease and mouse models. However, the mechanisms by which the reduction in lipid-filled adipocytes occurs during fibrosis are not well understood.
Here, we identify that adipocyte lipolysis via the rate limiting enzyme, adipocyte triglyceride lipase (Atgl), is required for loss of adipose tissue during skin fibrosis in mice. We find that in two fibrotic mouse models, adipocyte lipolysis occurs early during skin fibrosis development and lipid storage is reestablished during fibrosis recovery.
In mice lacking Atgl in adipocytes, maintenance of adipocyte lipid storage occurs in both chemical and genetic models of fibrosis development. Transcriptional analysis revealed upregulation of lipid metabolism/lipolysis genes in fibrotic patient skin.
Interestingly, loss of adipocyte Atgl-driven lipolysis results in precocious, fibrotic remodeling of the dermal ECM in bleomycin treated mice as indicated by histological and transcriptional changes. These data suggest that dermal adipocyte-derived fatty acids prevent fibrotic ECM remodeling in fibroblasts during fibrosis development.
Thus, we suggest that dermal adipocyte-derived fatty acids are released during fibrosis development and delay fibroblast fibrogenic responses, which may hold therapeutic potential for treating fibrotic diseases."
Atgl-dependent adipocyte lipolysis promotes lipodystrophy and restrains fibrogenic responses during skin fibrosis (open access)
Figure 3 Fibrotic lipodystrophy requires Atgl expression in adipocytes.
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