Division of Endocrinology, Diabetes, and Metabolism, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
The Cardiovascular Research Center and Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, USA.
Physiol Rep. 2022 Aug;10(16):e15424. doi: 10.14814/phy2.15424.
Adipose tissue secretes an abundance of lipid and protein mediators, and this secretome is depot-specific, with local and systemic effects on metabolic regulation. Intermuscular adipose tissue (IMAT) accumulates within the skeletal muscle compartment in obesity, and is associated with insulin resistance and metabolic disease. While the human IMAT secretome decreases insulin sensitivity in vitro, its composition is entirely unknown. The current study was conducted to investigate the composition of the human IMAT secretome, compared to that of the subcutaneous (SAT) and visceral adipose tissue (VAT) depots. IMAT, SAT, and VAT explants from individuals with obesity were used to generate conditioned media. Proteomics analysis of conditioned media was performed using multiplex proximity extension assays, and eicosanoid analysis using liquid chromatography-tandem mass spectrometry. Compared to SAT and/or VAT, IMAT secreted significantly more cytokines (IL2, IL5, IL10, IL13, IL27, FGF23, IFNγ and CSF1) and chemokines (MCP1, IL8, CCL11, CCL20, CCL25 and CCL27). Adipokines hepatocyte growth factor and resistin were secreted significantly more by IMAT than SAT or VAT. IMAT secreted significantly more eicosanoids (PGE TXB , 5-HETE, and 12-HETE) compared to SAT and/or VAT. In the context of obesity, IMAT is a distinct adipose tissue with a highly immunogenic and inflammatory secretome, and given its proximity to skeletal muscle, may be critical to glucose regulation and insulin resistance.
脂肪组织分泌大量的脂质和蛋白质介质，这些分泌物具有特定的储存库特异性，对代谢调节具有局部和全身作用。肌间脂肪组织（IMAT）在肥胖症中积聚在骨骼肌隔室中，与胰岛素抵抗和代谢疾病有关。虽然人类 IMAT 分泌组在体外降低胰岛素敏感性，但它的组成完全未知。本研究旨在研究人类 IMAT 分泌组的组成，与皮下（SAT）和内脏脂肪组织（VAT）储存库的组成进行比较。使用肥胖个体的 IMAT、SAT 和 VAT 外植体来生成条件培养基。使用多重邻近延伸测定法对条件培养基进行蛋白质组学分析，并使用液相色谱-串联质谱法对类二十烷酸进行分析。与 SAT 和/或 VAT 相比，IMAT 分泌的细胞因子（IL2、IL5、IL10、IL13、IL27、FGF23、IFNγ 和 CSF1）和趋化因子（MCP1、IL8、CCL11、CCL20、CCL25 和 CCL27）明显更多。IMAT 分泌的脂肪因子肝细胞生长因子和抵抗素明显多于 SAT 或 VAT。与 SAT 和/或 VAT 相比，IMAT 分泌的类二十烷酸（PGE TXB、5-HETE 和 12-HETE）明显更多。在肥胖的情况下，IMAT 是一种具有高度免疫原性和炎症性分泌组的独特脂肪组织，并且由于其靠近骨骼肌，可能对葡萄糖调节和胰岛素抵抗至关重要。
