Divergent functions of endotrophin on different cell populations in adipose tissue

Yueshui Zhao, Xue Gu, Ningyan Zhang, Mikhail G. Kolonin, Zhiqiang An, Kai Sun

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Endotrophin is a cleavage product of collagen 6 (Col6) in adipose tissue (AT). Previously, we demonstrated that endotrophin serves as a costimulator to trigger fibrosis and inflammation within the unhealthy AT milieu. However, how endotrophin affects lipid storage and breakdown in AT and how different cell types in AT respond to endotrophin stimulation remain unknown. In the current study, by using a doxycycline-inducible mouse model, we observed significant upregulation of adipogenic genes in the white AT (WAT) of endotrophin transgenic mice. We further showed that the mice exhibited inhibited lipolysis and accelerated hypertrophy and hyperplasia in WAT. To investigate the effects of endotrophin in vitro, we incubated different cell types from AT with conditioned medium from endotrophin- overexpressing 293T cells. We found that endotrophin activated multiple pathological pathways in different cell types. Particularly in 3T3-L1 adipocytes, endotrophin triggered a fibrotic program by upregulating collagen genes and promoted abnormal lipid accumulation by downregulating hormone-sensitive lipolysis gene and decreasing HSL phosphorylation levels. In macrophages isolated from WAT, endotrophin stimulated higher expression of the collagen-linking enzyme lysyl oxidase and M1 proinflammatory marker genes. In the stromal vascular fraction isolated from WAT, endotrophin induced upregulation of both profibrotic and proinflammatory genes. In conclusion, our study provides a new perspective on the effect of endotrophin in abnormal lipid accumulation and a mechanistic insight into the roles played by adipocytes and a variety of other cell types in AT in shaping the unhealthy microenvironment upon endotrophin treatment.

Original languageEnglish (US)
Pages (from-to)E952-E963
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume311
Issue number6
DOIs
StatePublished - Dec 1 2016

Fingerprint

Adipose Tissue
Population
Collagen
Genes
Lipolysis
Lipids
Adipocytes
endotrophin
Up-Regulation
Protein-Lysine 6-Oxidase
White Adipose Tissue
Doxycycline
HEK293 Cells
Conditioned Culture Medium
Hypertrophy
Transgenic Mice
Hyperplasia
Blood Vessels
Fibrosis
Down-Regulation

Keywords

  • Adipose tissue
  • Angiogenesis
  • Endotrophin
  • Fibrosis
  • Inflammation

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

Cite this

Divergent functions of endotrophin on different cell populations in adipose tissue. / Zhao, Yueshui; Gu, Xue; Zhang, Ningyan; Kolonin, Mikhail G.; An, Zhiqiang; Sun, Kai.

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 311, No. 6, 01.12.2016, p. E952-E963.

Research output: Contribution to journalArticle

Zhao, Yueshui ; Gu, Xue ; Zhang, Ningyan ; Kolonin, Mikhail G. ; An, Zhiqiang ; Sun, Kai. / Divergent functions of endotrophin on different cell populations in adipose tissue. In: American Journal of Physiology - Endocrinology and Metabolism. 2016 ; Vol. 311, No. 6. pp. E952-E963.
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