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KMID : 0620920230550030520
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Experimental & Molecular Medicine
2023 Volume.55 No. 3 p.520 ~ p.531
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TGFBI remodels adipose metabolism by regulating the Notch-1 signaling pathway
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Lee Seul-Gi
Chae Jong-Beom
Woo Seon-Min
Seo Seung-Un
Kim Ha-Jeong
Kim Sang-Yeob
David D. Schlaepfer
Kim In-San
Park Hee-Sae
Kwon Taeg-Kyu
Nam Ju-Ock
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Abstract
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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.
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KEYWORD
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Mechanisms of disease, Obesity
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