Stromal-vascular fraction content and adipose stem cell behavior are altered in morbid obese and post bariatric surgery ex-obese women

Abstract

IntroductionSubcutaneous adipose tissue is an interesting source of autologous stem cells with a fundamental role in the pathophysiology of obesity, metabolic syndromes and insulin resistance. We hypothesize that obesity could alter the stromal-vascular fraction (SVF) and adipose stem cell (ASCs) functions, which could compromise its regenerative behavior. Furthermore, we aimed to evaluate whether ASCs derived from post bariatric surgery ex-obese women maintain their functions in a similar fashion as do those from individuals who have never been obese.MethodsThe SVF of subcutaneous adipose tissue from control (n = 6, body mass index – BMI - 27.5 ± 0.5 kg/m2), obese (n = 12, BMI 46.2 ± 5.1 kg/m2) and post bariatric surgery ex-obese (n = 7, initial BMI 47.8 ± 1.3 kg/m2; final BMI 28.1 ± 1.1 kg/m2) women were isolated and evaluated by flow cytometry. ASCs were tested for lipid accumulation by perilipin, adipose differentiation-related protein (ADRP) and Oil Red O staining after adipogenic stimulus. The cytokines secreted by the ASCs and after lipid accumulation induction were also evaluated.ResultsThe subcutaneous adipose tissue of obese and post bariatric surgery ex-obese women was enriched in pericytes (p = 0.0345). The number of supra-adventitial cells was not altered in the obese patients, but it was highly enriched in the post bariatric surgery ex-obese women (p = 0.0099). The ASCs of the post bariatric surgery ex-obese patients secreted more MCP-1 (monocyte chemoattractant protein-1; p = 0.0078). After lipid accumulation induction, the ASCs of the patients in all groups secreted less IL-6 than the ASCs with no adipogenic stimulus (p < 0.0001). Obese ASCs with lipid accumulation secreted the highest amount of IL-6 (p < 0.001) whereas the ASCs from the controls secreted the highest amount of adiponectin (p < 0.0001). The ASCs from the post bariatric surgery ex-obese patients showed the highest levels of lipid accumulation whereas those from the obese women had the lowest levels (p < 0.0001).ConclusionsSVF content and ASC behavior are altered in the subcutaneous adipose tissue of morbid obese women; these changes are not completely restored after bariatric surgery-induced weight loss. The cellular alterations described in this study could affect the regenerative effects of adipose stem cells. Further investigations are required to avoid jeopardizing the development of autologous stem cell-based therapies.

Insight into the development of obesity: functional alterations of adipose‐derived mesenchymal stem cells

“…Furthermore, impaired ASCs could be a crucial step in deteriorating inflammation in adipose tissue. First, obese ASCs secrete pro‐inflammatory cytokines including TNF‐α, IL‐6, IL‐8 and MCP‐1 , which recruit peripheral monocytes and polarize them to M1 macrophages and contribute to insulin resistance and metabolic dysfunction. Second, obese ASCs are not able to promote angiogenesis by reducing their secretion of pro‐angiogenic factors like VEGF, HGF, FGF and platelet derived growth factor , resulting in impaired angiogenesis and fuelling hypoxia, adipocyte death and cellular stress in diseased obese tissue.…”

“…Second, obese ASCs are not able to promote angiogenesis by reducing their secretion of pro‐angiogenic factors like VEGF, HGF, FGF and platelet derived growth factor , resulting in impaired angiogenesis and fuelling hypoxia, adipocyte death and cellular stress in diseased obese tissue. Third, obese ASCs display a reduced adipogenic differentiation potential , losing their surveillance and repair function and deregulating further adipose tissue homeostasis. Fourth, obese ASCs show a diminished multipotency and self‐renewal capability , similar to aged ASCs undergoing numerous changes in inflammatory status, progenitor function and senescent cell induction .…”

“…This is further underlined by a study reporting that adipose tissue macrophages inhibited adipogenesis of mesenchymal precursor cells via the Wingless‐type MMTV integration site family 5 α (Wnt‐5α) signalling . In addition, obesity alters ASCs own secretion profile by producing pro‐inflammatory cytokines/chemokines , which fuels not only inflammation but also disrupts their own plasticity. Thus, the pro‐inflammatory factors impair directly the ASC differentiation potential and alter their regenerative capability.…”

“…Incubation with pro‐inflammatory cytokines from adipose tissue macrophages inhibited adipogenesis of adipocyte precursor cells in vitro . Lipid accumulation in ASCs derived from morbid obese patients was decreased after induction , suggestive of being less adipogenic differentiated. Obese ASCs differentiated much less toward adipogenic lineage than non‐obese control ASCs .…”

Adipocyte biology: It is time to upgrade to a new model

“…Obesity has numerous effects on the biology and function of ASCs that persist when these cells are maintained in cell culture, including reduced proliferative capacity, hypertrophy in the undifferentiated state (Pérez et al, , ), an impaired adipogenic response (Oñate et al, ; Pérez et al, ; Permana et al, ; Roldan et al, ; Van Harmelen et al, ), insulin resistance, and increased secretion of proinflammatory cytokines (Nair et al, ; Pérez et al, ; Pérez et al, ; Roldan et al, ; Silva et al, ; Zhou et al, ). The attenuated adipogenic response in obese‐derived ASC cultures is governed by a complex interplay of factors.…”