| Full text | |
| Author(s): Show less - |
Lino, Caroline A.
;
de Oliveira-Silva, Tabatha
;
Lunardon, Guilherme
;
Balbino-Silva, Camila
;
Lima, Vanessa M.
;
Huang, Zhan-Peng
;
Donato, Jose
;
Takano, Ana Paula C.
;
Barreto-Chaves, Maria Luiza
;
Wang, Da-Zhi
;
Diniz, Gabriela P.
Total Authors: 11
|
| Document type: | Journal article |
| Source: | MECHANISMS OF AGEING AND DEVELOPMENT; v. 210, p. 14-pg., 2023-01-16. |
| Abstract | |
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-offunction studies in vitro and in vivo revealed that miR-22 increases H2ax mRNA and gamma H2ax levels in preadipocytes and WAT without inducing DNA damage. Intriguingly, miR-22 ablation prevented HFD-induced increase in gamma H2ax levels and DNA damage in WAT. Similarly, miR-22 deletion prevented Doxo-induced increase in gamma H2ax 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. (AU) | |
| FAPESP's process: | 18/10338-2 - Role of microRNA-22 in differentiation of brown adipocytes and in browning of white adipose tissue |
| Grantee: | Gabriela Placoná Diniz |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 20/13211-3 - Impact of microRNA-22 and cellular senescence in obesity-induced metabolic dysfunctions |
| Grantee: | Gabriela Placoná Diniz |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 18/21491-6 - Impact of miRNA-22 and cell senescence in metabolic dysfunctions induced by obesity |
| Grantee: | Caroline Antunes Lino |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |