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オオツキ ミチオ
Ootsuki Michio
大月 道夫 所属 医学部 医学科（東京女子医科大学病院） 職種 教授・基幹分野長 |
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| 論文種別 | 原著 |
| 言語種別 | 英語 |
| 査読の有無 | 査読あり |
| 表題 | Transforming growth factor β1 signaling links extracellular matrix remodeling to intracellular lipogenesis upon physiological feeding events. |
| 掲載誌名 | 正式名：The Journal of biological chemistry 略 称：J Biol Chem ISSNコード：1083351X/00219258 |
| 掲載区分 | 国内 |
| 巻・号・頁 | 298(4),pp.101748 |
| 著者・共著者 | Toyoda Shinichiro, Shin Jihoon, Fukuhara Atsunori, Otsuki Michio, Shimomura Iichiro |
| 発行年月 | 2022/04 |
| 概要 | Adipose tissue dynamically changes its mass in response to external nutritional status, which plays an important role in maintaining the lipid homeostasis. Physiologically, feeding events are associated with the expansion of adipose tissue, but little is known about the detailed molecular mechanisms of this expansion. Here, using comprehensive transcriptome analysis, we found that levels of transforming growth factor β1 (TGF-β1), a key regulator of extracellular matrix (ECM) remodeling, were increased in adipose tissue under feeding conditions and associated with the lipogenic pathway. In addition, TGF-β receptors are highly expressed in adipose tissue, and pharmacological inhibition of TGF-β1 reduced adipose tissue mass and caused ectopic lipid accumulation in the liver. This reduced fat mass was associated with decreased gene expression in ECM remodeling and lipogenesis. Furthermore, similar results were observed in the adipose tissue of SMAD family member 3 knockout mice or upon systemic TGF-β neutralization, with significant reductions in both ECM remodeling and lipogenesis-related genes. Mechanistically, we found that insulin-induced TGF-β1 and cell-autonomous action remodels the ECM of adipocytes, which controls the downstream focal adhesion kinase-AKT signaling cascades and enhances the lipogenic pathway. Of note, destruction of collagens or matrix metalloproteinase/a disintegrin and metalloprotease activities, critical components of ECM remodeling, blocked TGF-β1-mediated focal adhesion kinase-AKT signaling and the lipogenic pathway. Taken together, this study identifies a previously unknown lipogenic role of TGF-β1 by which adipocytes can expand to adapt to physiological feeding events. |
| DOI | 10.1016/j.jbc.2022.101748 |
| PMID | 35189145 |