Fig. 1Adipose tissue distribution in human and heterogeneous characteristics between subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) in obese mice. (A) In human, adipose tissues are found in areas all over the body. In particular, brown adipose tissue is localized in neck, shoulder, and thorax to generate heat via higher activity of mitochondria and uncoupling protein-1 (UCP-1). VAT is localized in intra-abdomen and SAT is spread throughout the whole body. Both SAT and VAT have a higher capacity for lipid storage than brown adipose tissue. (B) In obese mice, SAT and VAT are differentially respond to obesity in many aspects such as immune responses, adipogenesis, and vasculatures. In obese mice, VAT exhibit elevated fibrosis and inflammatory responses accompanied with increased in vivo adipogenic potential. In contrast, such effects were rarely observed in obese SAT. Moreover, prolonged obesity reduces vasculature in obese VAT, whereas vasculature in obese SAT is denser than that in obese VAT.
Fig. 2Dissimilarity of vascularization and angiogenesis in subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) upon high-fat diet (HFD) feeding. Endothelial cells were stained with CD31 antibody conjugated with fluorescein isothiocyanate (FITC) fluorescence. Upon HFD feeding, vascular structures of visceral epididymal adipose tissue (EAT) are dramatically reduced compared to normal chow diet (NCD) fed mice. However, subcutaneous inguinal adipose tissue (IAT) in obesity maintains a similar degree of vasculatures compared to IAT in NCD condition. Scale bar indicates 100 µm.
Fig. 3Immune cells and pro-inflammatory responses in obesity. Normal and healthy adipose tissue harbors various types of anti-inflammatory immune cells such as M2-like macrophages (M2 MAC), eosinophils, helper T type 2 (TH2) cells, regulatory T (Treg) cells, and invariant natural killer T (iNKT) cells. These immune cells are involved in maintaining normal adipose functions and insulin sensitivity. In obesity, the number of pro-inflammatory immune cells including neutrophil, M1-like macrophages (M1 MAC), neutrophils, helper T type 1 (TH1) cells, Cytotoxic T (Tc) cells, and natural killer (NK) cells are elevated. In parallel, anti-inflammatory immune cells are decreased, leading to aggravation of adipose tissue inflammation and adipose dysfunction.
Fig. 4Subcutaneous and visceral adipogenic progenitors (APs) differentially respond to obesity and exert opposite effects on adipose tissue inflammation. Visceral APs are composed of mesothelial and mesodermal cells, but a certain portion of these cells lose adipogenic potential and are transformed into pro-inflammatory fibrocytes in obesity. The fibrotic-APs in visceral adipose tissue (VAT) exacerbate adipose tissue inflammation via inducing fibrosis and secreting pro-inflammatory cytokines. On the other hand, subcutaneous APs suppress pro-inflammatory macrophage infiltration into subcutaneous adipose tissue (SAT) in response to gamma-aminobutyric acid (GABA). Consequently, these anti-inflammatory effects on SAT would contribute to improvement of energy metabolism in obesity.
Table 1A list of surface marker genes identified for APs
Gene |
Discovery and identification |
Remark |
Reference |
CD10/NEP/cALLA |
Hematopoietic stem cells and mesenchymal tumour cells |
Alternative marker for mesenchymal stem cells |
Br J Haematol 1994;87:655-7 |
Arthritis Rheum 2002;46:3349-60 |
Ann N Y Acad Sci 2007;1106:262-71 |
Mod Pathol 2002;15:923-30 |
CD73/NT5E |
Placenta |
Mesenchymal stem cell marker |
Eur J Biochem 1990;191:563-9 |
Cytotherapy 2006;8:315-7 |
CD90/Thy-1 |
Thymocytes |
Mesenchymal and hematopoietic stem cell marker |
J Exp Med 1964;120:413-33 |
Am J Physiol Gastrointest Liver Physiol 2006;291:G45-54 |
CD105/Endoglin |
Mesenchymal stem cells |
Mesenchymal stem cell marker |
Biochem Biophys Res Commun 1999;265:134-9 |
CD31/PECAM-1 |
Endothelial cells |
Negative surface marker staining endothelial cell |
Science 1990;247:1219-22 |
Cell 2008;135:240-9 |
CD45/LCA |
Hematopoietic stem cells |
Negative surface marker staining hematopoietic immune cells |
Annu Rev Immunol 2003;21:107-37 |
Science 2008;322:583-6 |
Cell 2008;135:240-9 |
Ter119/Ly-76 |
Bone marrow cells |
Negative surface marker staining hematopoietic immune cells |
Cell 1990;62:863-74 |
Blood 2000;95:2559-68 |
Diabetes 2012;61:1691-9 |
Science 2008;322:583-6 |
CD34 |
Hematopoietic stem cells |
AP marker, but not mesenchymal stem cell marker |
J Immunol 1992;148:267-71 |
Cell 2008;135:240-9 |
Science 2008;322:583-6 |
Sca-1/Ly6a |
Hematopoietic stem cells |
AP marker |
Mol Cell Biol 1990;10:5150-9 |
Cell 2008;135:240-9 |
Science 2008;322:583-6 |
PDGFRα |
APs |
AP marker |
Cell Metab 2012;15:480-91 |
Cell Metab 2013;18:355-67 |
PDGFRβ |
Perivascular cells |
AP marker |
Science 2008;322:583-6 |
Elife 2018;7:e39636 |
CD24 |
Adipose stromal cells |
AP marker |
Cell 2008;135:240-9 |
DPP4 |
Adipose stromal cells |
Progenitor cell type marker of AP |
Science 2019;364:eaav2501 |
ICAM-1 |
Adipose stromal cells |
AP marker |
Science 2019;364:eaav2501 |