Adipogenic Impairment of Adipose Tissue-Derived Mesenchymal Stem Cells in Subjects With Metabolic Syndrome: Possible Protective Role of FGF2

J Clin Endocrinol Metab. 2017 Feb 1;102(2):478-487. doi: 10.1210/jc.2016-2256.

Abstract

Context: The decreased expansion capacity of adipose tissue plays a crucial role in the onset of disorders associated with metabolic syndrome.

Objective: The aim of this study was to examine the state of adipose tissue-derived mesenchymal stem cells (ASCs) from obese subjects with different metabolic profiles.

Design: This was a 2-year study to enroll subjects who underwent bariatric surgery or cholecystectomy.

Setting: University Hospital.

Patients and intervention: Patients who underwent either bariatric surgery (20 morbidly obese) or cholecystectomy (40 subjects) participated in the study.

Main outcome measures: ASCs were obtained from both visceral and subcutaneous adipose tissue. Adipogenic, fibrotic gene expression was quantified by quantitative polymerase chain reaction; Smad7 and fibroblast growth factor 2 were quantified by western blotting and enzyme-linked immunosorbent assay, respectively. The susceptibility of ASCs to apoptosis, their population doubling time, and their clonogenic potential were evaluated.

Results: The worsening metabolic profile of the patients was accompanied by a decrease in the intrinsic levels of adipogenic gene expression, reduced proliferation rate, clonogenic potential, and exportation of fibroblast growth factor 2 to the cell surface of the ASCs derived from both tissues. In addition, the ASCs from patients without metabolic syndrome showed differences in susceptibility to apoptosis and expression of TGFβ-signaling inhibitory protein Smad7 with respect to the ASCs from patients with metabolic syndrome.

Conclusion: Our results suggest that the decrease in adipogenic-gene mRNA and clonogenic potential, as well as the accumulation of fibrotic proteins with metabolic alterations, could be a relevant mechanism controlling the number and size of neogenerated adipocytes and involved in alteration of adipose-tissue expansion.

MeSH terms

  • Adipogenesis / genetics
  • Adipogenesis / physiology*
  • Adipose Tissue / metabolism
  • Adipose Tissue / pathology*
  • Adult
  • Anthropometry / methods
  • Apoptosis / physiology
  • Bariatric Surgery
  • Cell Differentiation / physiology
  • Cell Proliferation
  • Cholecystectomy
  • Colony-Forming Units Assay
  • Fibroblast Growth Factor 2 / metabolism
  • Fibroblast Growth Factor 2 / physiology*
  • Gene Expression Regulation / physiology
  • Glucose Transporter Type 4 / biosynthesis
  • Glucose Transporter Type 4 / genetics
  • Humans
  • Mesenchymal Stem Cells / metabolism
  • Mesenchymal Stem Cells / pathology
  • Mesenchymal Stem Cells / physiology*
  • Metabolic Syndrome / genetics
  • Metabolic Syndrome / metabolism
  • Metabolic Syndrome / pathology*
  • Middle Aged
  • Obesity, Morbid / metabolism
  • Obesity, Morbid / pathology
  • Obesity, Morbid / surgery
  • Perilipin-1 / biosynthesis
  • Perilipin-1 / genetics
  • RNA, Messenger / genetics

Substances

  • Glucose Transporter Type 4
  • PLIN1 protein, human
  • Perilipin-1
  • RNA, Messenger
  • SLC2A4 protein, human
  • Fibroblast Growth Factor 2