Graduate School of Health and Sports Science, Doshisha University, 1-3 Tatara-Miyakodani, Kyotanabe City, Kyoto, 610-0394, Japan; Japan Society for the Promotion of Sci., Tokyo, Japan.
Organization for Research Initiatives and Development, Doshisha University, 1-3 Tatara-Miyakodani, Kyotanabe City, Kyoto, 610-0394, Japan.
Biochem Biophys Res Commun. 2024 Nov 19;734:150447. doi: 10.1016/j.bbrc.2024.150447. Epub 2024 Jul 26.
Adipose-derived stem cell (ASC)-released exosomes (ASCexos) have multiple biological activities. We examined the effect of ASCexos derived from the inguinal adipose tissue of exercise-trained rats (EX-ASCexos) on adipogenic conversion of 3T3-L1 cells and analyzed their microRNA (miRNA) expression profiles. Differentiation of 3T3-L1 cells into adipocytes was performed for 9 d with EX-ASCexos or ASCexos from sedentary control rats (SED-ASCexos), and the expression of proteins and miRNA involved in adipogenic differentiation were determined. EX-ASCexos but not SED-ASCexos attenuated 3T3-L1 adipocyte differentiation with increased phosph-Ser112PPARγ expression, the inactive form of PPARγ. These differentiated adipocytes were also accompanied by increased phosph-Thr202/Tyr204ERK and decreased dual-specificity phosphatase 3 (DUSP3) levels. The exosomal miRNAs miR-323-5p, miR-433-3p, and miR-874-3p were identified specifically in EX-ASCexos. Of these, miR-323-5p mimic replicated the EX-ASCexo-induced suppression of 3T3-L1 adipocyte differentiation and altered adipogenesis-related factor expression. In conclusion, exercise training-driven exosomal miR-323-5p suppressed 3T3-L1 adipogenesis by increasing phosph-Ser112PPARγ expression, while phosph-Thr202/Tyr204ERK accumulation inhibited DUSP3 expression.
脂肪干细胞（ASC）释放的外泌体（ASCexos）具有多种生物学活性。我们研究了来源于运动训练大鼠腹股沟脂肪组织的 ASCexos（EX-ASCexos）对 3T3-L1 细胞成脂分化的影响，并分析了它们的 microRNA（miRNA）表达谱。用 EX-ASCexos 或来源于安静对照大鼠的 ASCexos（SED-ASCexos）对 3T3-L1 细胞进行 9 天的分化为脂肪细胞，测定参与成脂分化的蛋白质和 miRNA 的表达。EX-ASCexos 而非 SED-ASCexos 可增加磷酸化-Ser112PPARγ（PPARγ 的无活性形式）的表达，从而减弱 3T3-L1 脂肪细胞分化。这些分化的脂肪细胞还伴有磷酸化-Thr202/Tyr204ERK 增加和双特异性磷酸酶 3（DUSP3）水平降低。miR-323-5p、miR-433-3p 和 miR-874-3p 等外泌体 miRNA 特异性存在于 EX-ASCexos 中。其中，miR-323-5p 模拟物复制了 EX-ASCexo 诱导的 3T3-L1 脂肪细胞分化抑制作用，并改变了脂肪生成相关因子的表达。总之，运动训练驱动的外泌体 miR-323-5p 通过增加磷酸化-Ser112PPARγ 表达来抑制 3T3-L1 脂肪生成，而磷酸化-Thr202/Tyr204ERK 积累抑制 DUSP3 表达。
