Visceral and subcutaneous fat have different origins and evidence supports a mesothelial source

Abstract

Fuelled by the obesity epidemic, there is considerable interest in the developmental origins of white adipose tissue (WAT) and the stem/progenitor cells from which it arises. While increased visceral fat mass is associated with metabolic dysfunction, increased subcutaneous WAT is protective. There are 6 visceral fat depots: perirenal, gonadal, epicardial, retroperitoneal, omental and mesenteric and it is a subject of much debate whether these have common developmental origins and whether this differs from subcutaneous WAT. Here we show that all 6 visceral WAT depots receive a significant contribution from cells expressing Wt1 late in gestation. Conversely, no subcutaneous WAT or brown adipose tissue (BAT) arises from Wt1 expressing cells. Postnatally, a subset of visceral WAT continues to arise from Wt1 expressing cells, consistent with the finding that Wt1 marks a proportion of cell populations enriched in WAT progenitors. We show all visceral fat depots have a mesothelial layer like the visceral organs with which they are associated and provide several lines of evidence that Wt1 expressing mesothelium can produce adipocytes. These results: reveal a major ontogenetic difference between visceral and subcutaneous WAT; pinpoint the lateral plate mesoderm as a major source of visceral WAT; support the notion that visceral WAT progenitors are heterogeneous; and suggest that mesothelium is a source of adipocytes.