衰老
内分泌学
内科学
生物
白色脂肪组织
脂肪组织
脂肪细胞
DNA损伤
小RNA
医学
生物化学
DNA
基因
作者
Caroline Antunes Lino,Tábatha de Oliveira Silva,Guilherme Lunardon,Camila S. Balbino Silva,Vanessa Batista de Sousa Lima,Zhan-Peng Huang,José Donato,Ana Paula Cremasco Takano,Maria Luiza Barreto-Chaves,Dazhi Wang,Gabriela Placoná Diniz
标识
DOI:10.1016/j.mad.2023.111775
摘要
High-fat diet (HFD) promotes obesity-related metabolic complications by activating cellular senescence in white adipose tissue (WAT). Growing evidence supports the importance of microRNA-22 (miR-22) in metabolic disorders and cellular senescence. Recently, we showed that miR-22 deletion attenuates obesity-related metabolic abnormalities. However, whether miR-22 mediates HFD-induced cellular senescence of WAT remains unknown. Here, we uncovered that obese mice displayed increased pri-miR-22 levels and cellular senescence in WAT. However, miR-22 ablation protected mice against HFD-induced WAT senescence. In addition, in vitro studies showed that miR-22 deletion prevented preadipocyte senescence in response to Doxorubicin (Doxo). Loss-of-function studies in vitro and in vivo revealed that miR-22 increases H2ax mRNA and γH2ax levels in preadipocytes and WAT without inducing DNA damage. Intriguingly, miR-22 ablation prevented HFD-induced increase in γH2ax levels and DNA damage in WAT. Similarly, miR-22 deletion prevented Doxo-induced increase in γH2ax levels in preadipocytes. Adipose miR-22 levels were enhanced in middle-aged mice fed a HFD than those found in young mice. Furthermore, miR-22 deletion attenuated fat mass gain and glucose imbalance induced by HFD in middle-aged mice. Overall, our findings indicate that miR-22 is a key regulator of obesity-induced WAT senescence and metabolic disorders in middle-aged mice.
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