Obesity induced by high-fat diet is associated with critical changes in biological and molecular functions of mesenchymal stromal cells present in visceral adipose tissue

Aging (Albany NY). 2020 Dec 27;12(24):24894-24913. doi: 10.18632/aging.202423. Epub 2020 Dec 27.

Abstract

The mesenchymal stromal cells (MSCs) residing within the stromal component of visceral adipose tissue appear to be greatly affected by obesity, with impairment of their functions and presence of senescence. To gain further insight into these phenomena, we analyzed the changes in total proteome content and secretome of mouse MSCs after a high-fat diet (HFD) treatment compared to a normal diet (ND). In healthy conditions, MSCs are endowed with functions mainly devoted to vesicle trafficking. These cells have an immunoregulatory role, affecting leukocyte activation and migration, acute inflammation phase response, chemokine signaling, and platelet activities. They also present a robust response to stress. We identified four signaling pathways (TGF-β, VEGFR2, HMGB1, and Leptin) that appear to govern the cells' functions. In the obese mice, MSCs showed a change in their functions. The immunoregulation shifted toward pro-inflammatory tasks with the activation of interleukin-1 pathway and of Granzyme A signaling. Moreover, the methionine degradation pathway and the processing of capped intronless pre-mRNAs may be related to the inflammation process. The signaling pathways we identified in ND MSCs were replaced by MET, WNT, and FGFR2 signal transduction, which may play a role in promoting inflammation, cancer, and aging.

Keywords: mesenchymal stromal cells; senescence; visceral adipose tissue.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / metabolism*
  • Animals
  • Diet, High-Fat*
  • Granzymes / metabolism
  • HMGB1 Protein / metabolism
  • Inflammation / metabolism*
  • Interleukin-1 / metabolism
  • Intra-Abdominal Fat / cytology
  • Intra-Abdominal Fat / metabolism*
  • Leptin / metabolism
  • Mesenchymal Stem Cells / metabolism*
  • Methionine / metabolism
  • Mice
  • Obesity / metabolism*
  • Proteome
  • Proto-Oncogene Proteins c-met / metabolism
  • RNA Precursors / metabolism
  • RNA Processing, Post-Transcriptional
  • Receptor, Fibroblast Growth Factor, Type 2 / metabolism
  • Secretory Vesicles / metabolism
  • Signal Transduction
  • Transforming Growth Factor beta / metabolism
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism
  • Wnt Signaling Pathway

Substances

  • HMGB1 Protein
  • Interleukin-1
  • Leptin
  • Proteome
  • RNA Precursors
  • Transforming Growth Factor beta
  • Methionine
  • Proto-Oncogene Proteins c-met
  • Receptor, Fibroblast Growth Factor, Type 2
  • Vascular Endothelial Growth Factor Receptor-2
  • Granzymes