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

• Published in: The journal of clinical endocrinology and metabolism Vol. 102; no. 2; pp. 478 - 487
• Main Authors: Oliva-Olivera, Wilfredo, Coín-Aragüez, Leticia, Lhamyani, Said, Clemente-Postigo, Mercedes, Torres, Juan Alcaide, Bernal-López, Maria Rosa, El Bekay, Rajaa, Tinahones, Francisco José
• Format: Journal Article
• Language: English
• Published: Washington, DC Endocrine Society 01.02.2017; Copyright Oxford University Press; Oxford University Press
• Subjects: Adipocytes; Adipogenesis - genetics; Adipogenesis - physiology; Adipose tissue; Adipose Tissue - metabolism; Adipose Tissue - pathology; Adult; Anthropometry - methods; Apoptosis; Apoptosis - physiology; Bariatric Surgery; Body fat; Cell Differentiation - physiology; Cell Proliferation; Cell surface; Cholecystectomy; Colony-Forming Units Assay; Enzyme-linked immunosorbent assay; Fibroblast growth factor 2; Fibroblast Growth Factor 2 - metabolism; Fibroblast Growth Factor 2 - physiology; Fibroblasts; Gastrointestinal surgery; Gene expression; Gene Expression Regulation - physiology; Glucose Transporter Type 4 - biosynthesis; Glucose Transporter Type 4 - genetics; Growth factors; Humans; Mesenchymal stem cells; Mesenchymal Stromal Cells - metabolism; Mesenchymal Stromal Cells - pathology; Mesenchymal Stromal Cells - physiology; Mesenchyme; Metabolic syndrome; Metabolic Syndrome - genetics; Metabolic Syndrome - metabolism; Metabolic Syndrome - pathology; Middle Aged; Obesity, Morbid - metabolism; Obesity, Morbid - pathology; Obesity, Morbid - surgery; Patients; Perilipin-1 - biosynthesis; Perilipin-1 - genetics; Polymerase chain reaction; RNA, Messenger - genetics; Smad7 protein; Stem cells; Surgery; Western blotting
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2016-2256

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.We studied the state of ASCs from obese patients with different metabolic profiles. ASC impairment could contribute to the decrease in adipose-tissue expandability in metabolic syndrome.