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


METHODS
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.
Department of Surgery, Duke University Medical Center, 407 Crutchfield St, Durham, NC 27704, USA.
Jie-Gen
JG
Chen
Anna
A
Spagnoli
Alfonso
A
Torquati
D017667:Adipocytes / Q000166:cytology*; D000273:Adipose Tissue / Q000166:cytology*; D000328:Adult; D002454:Cell Differentiation; D002478:Cells, Cultured; D015390:Gastric Bypass; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D008875:Middle Aged; D009765:Obesity / Q000601:surgery*