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Adipogenic differentiation of adipose tissue-derived human mesenchymal stem cells: effect of gastric bypass surgery

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Abstract

Background

Adipose tissue dysfunction is an important feature of obesity characterized by enlarged adipocytes and marked changes in secretion of cytokines. These changes result in insulin resistance, chronic vascular inflammation, oxidative stress, and activation of the renin–angiotensin system (RAS), eventually leading to type 2 diabetes, obesity-related hypertension, and cardiovascular disease (CVD). Several trials have shown that bariatric surgery significantly reduces these comorbidities. However, there is a gap in knowledge regarding the mechanisms whereby bariatric surgery reduces the burden of CVD in obese individuals.

Method

Mesenchymal stem cells (MSCs) were isolated from adipose tissue collected from three groups: (1) nonobese control subjects, (2) obese subjects undergoing gastric bypass surgery (GBS), and (3) subjects 1 year or more after GBS. In the study, MSCs were induced to adipogenic differentiation, and RAS-related gene expressions were determined by quantitative polymerase chain reaction. The effect of angiotensin II (Ang II) on adipogenic differentiation of MSCs also was investigated.

Results

Angiotensinogen mRNA levels in MSCs and differentiated adipocytes were significantly higher in the obese group than in the nonobese control subjects. Renin mRNA levels were significantly higher in the obese group MSCs than in the nonobese and post-GBS groups. Angiotensin-converting enzyme mRNA levels were significantly lower in the MSCs derived from the post-GBS group than in the obese and nonobese control subjects. Serum Ang II levels were significantly lower in the post-GBS group (52.1 ± 4.2 pg/ml) than in the nonobese (85.4 ± 12.4 pg/ml) and obese (84.7 ± 10.0 pg/ml) groups. Ang II treatment inhibited adipogenesis of MSCs in a dose-dependent manner. The inhibitory effect of Ang II was mainly abolished by PD123319, a receptor 2 blocker.

Conclusions

The adipogenesis of MSCs is inhibited by Ang II treatment. Obese individuals are characterized by an upregulation of the RAS-related gene expressions in adipose tissue. This upregulation resolves in post-GBS subjects.

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Acknowledgments

The study was supported by a SAGES Research Grant Award and an NIH K23 DK07597 award to A.T. The authors thank all the participants in this study.

Disclosures

Jie-Gen Chen, Anna Spagnoli, and Alfonso Torquati have no conflicts of interest or financial ties to disclose.

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Authors and Affiliations

  1. Department of Surgery, Duke University Medical Center, 407 Crutchfield St, Durham, NC, 27704, USA

    Jie-Gen Chen & Alfonso Torquati

  2. Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA

    Anna Spagnoli

Authors
  1. Jie-Gen Chen
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  2. Anna Spagnoli
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  3. Alfonso Torquati
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Corresponding author

Correspondence to Alfonso Torquati.

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Chen, JG., Spagnoli, A. & Torquati, A. Adipogenic differentiation of adipose tissue-derived human mesenchymal stem cells: effect of gastric bypass surgery. Surg Endosc 26, 3449–3456 (2012). https://doi.org/10.1007/s00464-012-2353-x

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  • DOI: https://doi.org/10.1007/s00464-012-2353-x

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