Abstract
Fat accumulation and the dysfunction of visceral white adipose tissue (WAT), but not subcutaneous WAT, cause abnormalities in whole body metabolic homeostasis. However, no current drugs specifically target visceral WAT. The primary reason for this is that a practical in vitro culture system for mesenteric adipocytes has not been established. To resolve this issue, we sought to identify in vitro adipogenic cells in mesenteric and subcutaneous WATs. First, we examined the expression pattern of surface antigens in stromal-vascular fraction (SVF) cells from mouse mesenteric and subcutaneous WATs, and found the expression of 30 stem cell-related surface antigens. Then, to evaluate the adipogenic ability of each fraction, we performed in vitro screening, and identified five candidate markers for mesenteric adipogenic cells and one candidate marker for subcutaneous adipogenic cells. To investigate whether in vitro adipogenic ability accurately reflects the conditions in vivo, we performed transplantation experiments, and identified CD9− CD201+ Sca-1− cells and CD90+ cells as mesenteric and subcutaneous in vitro adipogenic cells, respectively. Furthermore, mature adipocytes derived from mesenteric and subcutaneous adipogenic cells maintained each characteristic phenotype in vitro. Thus, our study should contribute to the development of a useful culture system for visceral adipocytes.
Highlights
White adipose tissue (WAT) is anatomically classified into intra-abdominal visceral white adipose tissue (WAT) and subcutaneous WAT1
Isolated Stromal-vascular fraction (SVF) cells from mesenteric and subcutaneous WATs were gated into Lin− CD29+ CD34+ fibroblasts according to a previous report[22], and antigen expression was tested in this fraction (Fig. 1)
As SSEA-3 was not expressed in Lin− CD29+ CD34+ fibroblasts from mesenteric WAT, this antigen was assessed only in cells derived from subcutaneous WAT (Supplementary Fig. S1-2)
Summary
White adipose tissue (WAT) is anatomically classified into intra-abdominal visceral WAT and subcutaneous WAT1. But not subcutaneous, WAT fat accumulation and dysfunction cause abnormalities in whole body metabolic homeostasis resulting in life-threatening disorders[1]. In human obesity, increased lipolysis in accumulated visceral WAT results in a greater release of free fatty acids into the portal vein, and exposes the liver to high concentrations of free fatty acids, causing metabolic abnormalities[1,6]. There are cell culture models for the molecular analysis of adipocytes, including 3T3-L1, 3T3-F442, C3H10T1/2, and Ob1711,12. These cell lines are derived from mouse embryos or epididymal WAT, which means they cannot be used to examine the function of distinct fat depots, such as visceral or subcutaneous WATs. Primary culture cells are another model type. CD36 CD38 CD40 CD41 CD43 CD44 CD47 CD48 CD49b CD49d CD49e CD49f CD51 CD54 CD55 CD56 CD59 CD71 CD73 CD79a
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