National Medical Research Centre of Cardiology named after academician E.I.Chazov, 121552, Moscow, Russia.
Lomonosov Moscow State University, 119991, Moscow, Russia.
Int J Obes (Lond). 2023 Aug;47(8):732-742. doi: 10.1038/s41366-023-01317-1. Epub 2023 Apr 26.
In recent years, there has been an increase in the prevalence of obesity and type 2 diabetes mellitus (T2DM). Development of visceral instead of subcutaneous adipose tissue is pathogenic and increases the risk of metabolic abnormalities. We hypothesize that visceral adipocytes and stromal cells are able to deteriorate other fat depots metabolism via secretory mechanisms.
We study the regulatory role of visceral adipose-derived stem cells (vADSC) from donors with obesity and T2DM or normal glucose tolerance (NGT) on healthy subcutaneous ADSC (sADSC) in the Transwell system. Lipid droplets formation during adipogenesis was assessed by confocal microscopy. Cell metabolism was evaluated by 14C-glucose incorporation analysis and western blotting. vADSC secretome was assessed by Milliplex assay.
We showed that both NGT and T2DM vADSC had mesenchymal phenotype, but expression of CD29 was enhanced, whereas expressions of CD90, CD140b and IGF1R were suppressed in both NGT and T2DM vADSC. Co-differentiation with T2DM vADSC increased lipid droplet size and stimulated accumulation of fatty acids in adipocytes from healthy sADSC. In mature adipocytes T2DM vADSC stimulated triglyceride formation, whereas NGT vADSC activated oxidative metabolism. Secretome of NGT vADSC was pro-inflammatory and pro-angiogenic in comparison with T2DM vADSC.
The present study has demonstrated the critical role of secretory interactions between visceral and subcutaneous fat depots both in the level of progenitor and mature cells. Mechanisms of these interactions are related to direct exchange of metabolites and cytokines secretion.
近年来，肥胖和 2 型糖尿病（T2DM）的患病率有所上升。内脏脂肪而非皮下脂肪的增加与发病机制相关，并增加了代谢异常的风险。我们假设内脏脂肪细胞和基质细胞能够通过分泌机制使其他脂肪组织代谢恶化。
我们在 Transwell 系统中研究了肥胖和 T2DM 或正常糖耐量（NGT）供体的内脏脂肪衍生干细胞（vADSC）对健康皮下脂肪衍生干细胞（sADSC）的调节作用。通过共聚焦显微镜评估脂肪生成过程中脂滴的形成。通过 14C-葡萄糖掺入分析和 Western blot 评估细胞代谢。通过 Milliplex 测定法评估 vADSC 分泌组。
我们表明，NGT 和 T2DM vADSC 均具有间充质表型，但 CD29 的表达增强，而 NGT 和 T2DM vADSC 的 CD90、CD140b 和 IGF1R 表达均受抑制。与 T2DM vADSC 共分化增加了健康 sADSC 脂肪细胞中的脂滴大小并刺激脂肪酸的积累。在成熟脂肪细胞中，T2DM vADSC 刺激甘油三酯的形成，而 NGT vADSC 激活氧化代谢。与 T2DM vADSC 相比，NGT vADSC 的分泌组具有促炎和促血管生成作用。
本研究表明，内脏和皮下脂肪组织之间的分泌相互作用在祖细胞和成熟细胞水平上都具有重要作用。这些相互作用的机制与代谢物和细胞因子分泌的直接交换有关。
