Department of Food Science and Biotechnology, Kyungpook National University, Daegu, 41566, Republic of Korea.
Department of Immunology, School of Medicine, Keimyung University, Daegu, 42601, Republic of Korea.
Exp Mol Med. 2023 Mar;55(3):520-531. doi: 10.1038/s12276-023-00947-9. Epub 2023 Mar 1.
Extracellular matrix proteins are associated with metabolically healthy adipose tissue and regulate inflammation, fibrosis, angiogenesis, and subsequent metabolic deterioration. In this study, we demonstrated that transforming growth factor-beta (TGFBI), an extracellular matrix (ECM) component, plays an important role in adipose metabolism and browning during high-fat diet-induced obesity. TGFBI KO mice were resistant to adipose tissue hypertrophy, liver steatosis, and insulin resistance. Furthermore, adipose tissue from TGFBI KO mice contained a large population of CD11b and CD206 M2 macrophages, which possibly control adipokine secretion through paracrine mechanisms. Mechanistically, we showed that inhibiting TGFBI-stimulated release of adipsin by Notch-1-dependent signaling resulted in adipocyte browning. TGFBI was physiologically bound to Notch-1 and stimulated its activation in adipocytes. Our findings revealed a novel protective effect of TGFBI deficiency in obesity that is realized via the activation of the Notch-1 signaling pathway.
细胞外基质蛋白与代谢健康的脂肪组织有关，并调节炎症、纤维化、血管生成以及随后的代谢恶化。在这项研究中，我们证明转化生长因子-β（TGFBI），一种细胞外基质（ECM）成分，在高脂肪饮食诱导肥胖期间的脂肪代谢和棕色化中发挥重要作用。TGFBI 敲除小鼠抵抗脂肪组织肥大、肝脂肪变性和胰岛素抵抗。此外，TGFBI 敲除小鼠的脂肪组织中含有大量的 CD11b 和 CD206 M2 巨噬细胞，它们可能通过旁分泌机制控制脂肪因子的分泌。从机制上讲，我们表明 Notch-1 依赖性信号抑制 TGFBI 刺激的脂联素释放会导致脂肪细胞棕色化。TGFBI 与 Notch-1 生理性结合并刺激其在脂肪细胞中的激活。我们的研究结果揭示了 TGFBI 缺乏在肥胖中的一种新的保护作用，该作用是通过 Notch-1 信号通路的激活来实现的。
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