TGFBI remodels adipose metabolism by regulating the Notch-1 signaling pathway.
TGFBI remodels adipose metabolism by regulating the Notch-1 signaling pathway.
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DOI：
10.1038/s12276-023-00947-9
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发表时间：
2023-03
影响因子：
12.8
通讯作者：
Nam, Ju-Ock
中科院分区：
文献类型：
--
作者：
Lee, Seul Gi;Chae, Jongbeom;Woo, Seon Min;Seo, Seung Un;Kim, Ha-Jeong;Kim, Sang-Yeob;Schlaepfer, David D.;Kim, In-San;Park, Hee-Sae;Kwon, Taeg Kyu;Nam, Ju-Ock
细胞外基质蛋白与代谢健康的脂肪组织相关，并调节炎症、纤维化、血管生成和随后的代谢恶化。在这项研究中，我们证明了转化生长因子-β (TGFBI)，一种细胞外基质 (ECM) 成分，在高脂饮食诱导的肥胖期间的脂肪代谢和褐变中发挥着重要作用。 TGFBI KO 小鼠对脂肪组织肥大、肝脏脂肪变性和胰岛素抵抗具有抵抗力。此外，TGFBI KO小鼠的脂肪组织含有大量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，我们发现通过Notch-1依赖性信号传导抑制TGFBI刺激的adipsin释放会导致脂肪细胞褐变。 TGFBI 在生理上与 Notch-1 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 缺乏对肥胖症的一种新的保护作用，这种作用是通过激活 Notch-1 信号通路来实现的。研究一种调节脂肪扩张的名为 TGFBI 的蛋白质，可能有助于开发预防肥胖和相关代谢紊乱（如 II 型糖尿病）的新方法。白色脂肪组织（身体脂肪）储存能量，棕色脂肪组织产生热量。促进脂肪组织“褐变”可能有助于预防肥胖。影响脂肪微环境的蛋白质可能与代谢疾病有关，因此韩国庆北国立大学的 Seul Gi Lee 和 Ju-Ock Nam、韩国大邱启明大学的 Taeg Kyu Kwon 及其同事研究了 TGFBI 如何影响小鼠模型中的脂肪代谢。删除小鼠体内的 TGFBI 可促进白色脂肪组织转化为棕色脂肪，从而防止小鼠体重增加和脂肪组织增加。这些结果为通过 TGFBI 调节治疗肥胖和相关疾病的潜在疗法提供了见解。
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. Studying a protein called TGFBI, which regulates adipose expansion, may help the development of new approaches to protect against obesity and related metabolic disorders such as type II diabetes. White adipose tissue (body fat) stores energy, and brown adipose tissue generates heat. Promoting “browning” of adipose tissue may help protect against obesity. Proteins that influence adipose microenvironment can be involved in metabolic diseases, so Seul Gi Lee and Ju-Ock Nam at Kyungpook National University, Taeg Kyu Kwon at Keimyung University, both in Daegu, South Korea, and co-workers investigated how TGFBI affects adipose metabolism in a mouse model. Deleting TGFBI in mice promoted the transformation of white adipose tissue to brown, protecting mice against weight gain and increase in adipose tissue. These results offer insights into potential therapies for obesity and related disorders via TGFBI regulation.
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影响因子：
37.8
作者：
Gealekman O;Guseva N;Hartigan C;Apotheker S;Gorgoglione M;Gurav K;Tran KV;Straubhaar J;Nicoloro S;Czech MP;Thompson M;Perugini RA;Corvera S
通讯作者：
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影响因子：
7.7
作者：
Bonner, Jeffrey S.;Lantier, Louise;Wasserman, David H.
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作者：
Lo JC;Ljubicic S;Leibiger B;Kern M;Leibiger IB;Moede T;Kelly ME;Chatterjee Bhowmick D;Murano I;Cohen P;Banks AS;Khandekar MJ;Dietrich A;Flier JS;Cinti S;Blüher M;Danial NN;Berggren PO;Spiegelman BM
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Spiegelman BM
影响因子：
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作者：
Garces, C;RuizHidalgo, MJ;Laborda, J
通讯作者：
Laborda, J
影响因子：
7.5
作者：
Kim, Jin Soo;Lee, Seul Gi;Nam, Ju-Ock
通讯作者：
Nam, Ju-Ock