焦点粘着
脂肪生成
脂肪细胞
细胞外基质
脂肪组织
细胞生物学
整合素
化学
内科学
内分泌学
白色脂肪组织
下调和上调
磷酸化
信号转导
激酶
生物
生物化学
医学
细胞
基因
作者
You-e Yan,Xiyue Yan,Ao Sun,Li Zhang,Jing Zhang
标识
DOI:10.1002/mnfr.202101088
摘要
High-fat-diet (HFD) is an important factor in obesity. Extracellular matrix (ECM) regulates white adipose tissue (WAT), but its mechanism is unknown.This study uses three models-HFD-fed mice, human with obesity, and 3T3-L1 adipocytes with oleic acid (OA)/macromolecular crowders (MMC) treatment. Glucose and lipids metabolic disorders, increased collagen I/IV and laminin α2/4 (LAMA2/4), and upregulated integrins (ITGA1/ITGA7) - focal adhesion kinase (FAK) - c-Jun N-terminal kinase (JNK)/extracellular regulated protein kinase 1/2 (ERK1/2) signals in obese WAT from mice and human are observed. The upregulation of ECM - integrin - FAK signals is stronger in subcutaneous WAT than that in visceral WAT of mice, but these results are reversed in human. In vitro, oleic acid (OA) promotes lipid accumulation and upregulates collagen IV, LAMA4, and p-JNK. MMC is used to induce ECM deposition in adipocytes. MMC promotes adipocyte differentiation and integrins - FAK - JNK/ERK1/2 signals. When FAK phosphorylation is inhibited, downstream p-JNK is decreased. Inhibition of FAK phosphorylation reduces adipocyte differentiation, but MMC partially reverses this effect.HFD-induced ECM deposition, whose signals are transmitted into adipocytes through upregulating ITGA1/ITGA7, activates the phosphorylation of intracellular FAK - JNK/ERK1/2 signals, and promotes adipogenesis in WAT. This mechanism provides novel therapeutic targets to treat obesity.
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