新しい細胞が肥満治療の鍵となる可能性(New cells could be key to treating obesity)

2024-05-16

2024-05-15 スイス連邦工科大学ローザンヌ校(EPFL)

脂肪組織の形成と機能を理解することは肥満や代謝疾患の対策に重要です。体内での位置により脂肪組織の特性は異なります。大網脂肪は免疫調節や組織再生に関与し、肥大によって代謝疾患リスクを高める「リンゴ型」体型を引き起こします。大網脂肪は新しい脂肪細胞の形成(脂肪生成)よりも既存の脂肪細胞の拡大(肥大)を通じて増加します。
◆EPFLのBart Deplancke教授のチームは、大網脂肪組織に脂肪生成を妨げる細胞を特定しました。これらの細胞はインスリン様成長因子結合タンパク質2(IGFBP2)を高レベルで発現し、脂肪幹細胞の成熟を阻害します。この発見は肥満管理に新たな視点を提供します。

<関連情報>

ヒトの大腿骨に特異的な中皮様間質集団が、IGFBP2分泌を介して脂肪形成を抑制する A human omentum-specific mesothelial-like stromal population inhibits adipogenesis through IGFBP2 secretion

Radiana Ferrero, Pernille Yde Rainer, Marie Rumpler, Julie Russeil, Magda Zachara, Joern Pezoldt, Guido van Mierlo, Vincent Gardeux, Wouter Saelens, Daniel Alpern, Lucie Favre, Nathalie Vionnet, Styliani Mantziari, Tobias Zingg, Nelly Pitteloud, Michel Suter, Maurice Matter, Kai-Uwe Schlaudraff, Carles Canto, Bart Deplancke
Metabolism Published: May 9, 2024
DOI:https://doi.org/10.1016/j.cmet.2024.04.017

Highlights

A single-cell transcriptomic atlas integrating Lin- SVF cells from four different human adipose depots
In-depth transcriptional analysis of stromal populations across four human adipose depots
Adipogenic characterization of five stromal populations across three human adipose depots
Omental-specific cells characterized by high IGFBP2 expression repress adipogenesis

Summary

Adipose tissue plasticity is orchestrated by molecularly and functionally diverse cells within the stromal vascular fraction (SVF). Although several mouse and human adipose SVF cellular subpopulations have by now been identified, we still lack an understanding of the cellular and functional variability of adipose stem and progenitor cell (ASPC) populations across human fat depots. To address this, we performed single-cell and bulk RNA sequencing (RNA-seq) analyses of >30 SVF/Lin- samples across four human adipose depots, revealing two ubiquitous human ASPC (hASPC) subpopulations with distinct proliferative and adipogenic properties but also depot- and BMI-dependent proportions. Furthermore, we identified an omental-specific, high IGFBP2-expressing stromal population that transitions between mesothelial and mesenchymal cell states and inhibits hASPC adipogenesis through IGFBP2 secretion. Our analyses highlight the molecular and cellular uniqueness of different adipose niches, while our discovery of an anti-adipogenic IGFBP2+ omental-specific population provides a new rationale for the biomedically relevant, limited adipogenic capacity of omental hASPCs.