TGFBI remodels adipose metabolism by regulating the Notch-1 signaling pathway

Seul Gi Lee; Jongbeom Chae; Seon Min Woo; Seung Un Seo; Ha Jeong Kim; Sang Yeob Kim; David D. Schlaepfer; In San Kim; Hee Sae Park; Taeg Kyu Kwon; Ju Ock Nam

doi:10.1038/s12276-023-00947-9

TGFBI remodels adipose metabolism by regulating the Notch-1 signaling pathway

Seul Gi Lee, Jongbeom Chae, Seon Min Woo, Seung Un Seo, Ha Jeong Kim, Sang Yeob Kim, David D. Schlaepfer, In San Kim, Hee Sae Park, Taeg Kyu Kwon, Ju Ock Nam

Research output: Contribution to journal › Article › peer-review

19 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	520-531
Number of pages	12
Journal	Experimental and Molecular Medicine
Volume	55
Issue number	3
DOIs	https://doi.org/10.1038/s12276-023-00947-9
State	Published - Mar 2023

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title = "TGFBI remodels adipose metabolism by regulating the Notch-1 signaling pathway",

abstract = "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.",

author = "Lee, \{Seul Gi\} and Jongbeom Chae and Woo, \{Seon Min\} and Seo, \{Seung Un\} and Kim, \{Ha Jeong\} and Kim, \{Sang Yeob\} and Schlaepfer, \{David D.\} and Kim, \{In San\} and Park, \{Hee Sae\} and Kwon, \{Taeg Kyu\} and Nam, \{Ju Ock\}",

note = "Publisher Copyright: {\textcopyright} 2023, The Author(s).",

year = "2023",

month = mar,

doi = "10.1038/s12276-023-00947-9",

language = "English",

volume = "55",

pages = "520--531",

journal = "Experimental and Molecular Medicine",

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T1 - TGFBI remodels adipose metabolism by regulating the Notch-1 signaling pathway

AU - Lee, Seul Gi

AU - Chae, Jongbeom

AU - Woo, Seon Min

AU - Seo, Seung Un

AU - Kim, Ha Jeong

AU - Kim, Sang Yeob

AU - Schlaepfer, David D.

AU - Kim, In San

AU - Park, Hee Sae

AU - Kwon, Taeg Kyu

AU - Nam, Ju Ock

PY - 2023/3

Y1 - 2023/3

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/85149039738

U2 - 10.1038/s12276-023-00947-9

DO - 10.1038/s12276-023-00947-9

M3 - Article

C2 - 36854775

AN - SCOPUS:85149039738

SN - 1226-3613

VL - 55

SP - 520

EP - 531

JO - Experimental and Molecular Medicine

JF - Experimental and Molecular Medicine

IS - 3

ER -

TGFBI remodels adipose metabolism by regulating the Notch-1 signaling pathway

Abstract

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