FSP1-positive fibroblasts are adipogenic niche and regulate adipose homeostasis

Rui Zhang; Yuan Gao; Xiaotong Zhao; Mei Gao; Yanjun Wu; Yingying Han; Yuemei Qiao; Zheng Luo; Li Yang; Jianfeng Chen; Gaoxiang Ge

doi:10.1371/journal.pbio.2001493

FSP1-positive fibroblasts are adipogenic niche and regulate adipose homeostasis

PLoS Biol. 2018 Aug 6;16(8):e2001493. doi: 10.1371/journal.pbio.2001493. eCollection 2018 Aug.

Authors

Rui Zhang^{1

2

3

4}, Yuan Gao^{1

2

3}, Xiaotong Zhao^{1

2

3

4}, Mei Gao^{1

2

3}, Yanjun Wu^{1

2

3}, Yingying Han^{1

2

3

4}, Yuemei Qiao^{1

2

3}, Zheng Luo^{4

5}, Li Yang^{4

5}, Jianfeng Chen^{1

4}, Gaoxiang Ge^{1

2

3

4}

Affiliations

¹ State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China.
² CAS Key Laboratory of Systems Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China.
³ Innovation Center for Cell Signaling Network, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China.
⁴ University of Chinese Academy of Sciences, Beijing, China.
⁵ CAS Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.

Abstract

Adipocyte progenitors reside in the stromal vascular fraction (SVF) of adipose tissues that are composed of fibroblasts, immune cells, and endothelial cells. It remains to be elucidated how the SVF regulates adipocyte progenitor fate determination and adipose homeostasis. Here, we report that fibroblast-specific protein-1 (FSP1)+ fibroblasts in the SVF are essential to adipose homeostasis. FSP1+ fibroblasts, devoid of adipogenic potential, are adjacent to the preadipocytes in the SVF. Ablation of FSP1+ fibroblasts in mice severely diminishes fat content of adipose depots. Activation of canonical Wnt signaling in the FSP1+ fibroblasts results in gradual loss of adipose tissues and resistance to diet-induced obesity. Alterations in the FSP1+ fibroblasts reduce platelet-derived growth factor (PDGF)-BB signaling and result in the loss of preadipocytes. Reduced PDGF-BB signaling, meanwhile, impairs the adipogenic differentiation capability of preadipocytes by regulating matrix metalloproteinase (MMP) expression, extracellular matrix remodeling, and the activation of Yes-associated protein (YAP) signaling. Thus, FSP1+ fibroblasts are an important niche essential to the maintenance of the preadipocyte pool and its adipogenic potential in adipose homeostasis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adaptor Proteins, Signal Transducing / genetics
Adaptor Proteins, Signal Transducing / metabolism
Adipocytes / cytology
Adipocytes / metabolism*
Adipose Tissue / cytology
Adipose Tissue / metabolism*
Animals
Becaplermin / genetics
Becaplermin / metabolism*
Cell Cycle Proteins
Cell Differentiation
Diet, High-Fat / adverse effects
Extracellular Matrix
Fibroblasts / cytology
Fibroblasts / metabolism*
Gene Expression Regulation
Homeostasis / genetics*
Male
Matrix Metalloproteinases / genetics
Matrix Metalloproteinases / metabolism
Mice
Mice, Transgenic
Obesity / etiology
Obesity / genetics*
Obesity / metabolism
Obesity / pathology
Phosphoproteins / genetics
Phosphoproteins / metabolism
S100 Calcium-Binding Protein A4 / genetics*
S100 Calcium-Binding Protein A4 / metabolism
Stem Cells / cytology
Stem Cells / metabolism
Wnt Signaling Pathway
YAP-Signaling Proteins

Substances

Adaptor Proteins, Signal Transducing
Cell Cycle Proteins
Phosphoproteins
S100 Calcium-Binding Protein A4
S100a4 protein, mouse
YAP-Signaling Proteins
Yap1 protein, mouse
Becaplermin
Matrix Metalloproteinases

Grants and funding

National Natural Science Foundation of China (grant number 81430067 and 31190061). (Received by GG). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Strategic Priority Research Program of the Chinese Academy of Sciences (grant number XDA12010100). (Received by GG). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. CAS/SAFEA International Partnership Program for Creative Research Teams. (Received by GG and JC). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. SA-SIBS Scholarship Program. (Received by GG and JC). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.