Unveiling the Role of Mir-186 in Sirt1 Regulation in Adipocytes: Implications for Adipogenesis and Inflammation in Obesity Publisher



Tamkini M¹ ; Nourbakhsh M^{2, 3} ; Movahedi M¹ ; Golestani A⁴ Show Affiliations
Source: Journal of Diabetes and Metabolic Disorders Published:2025

Abstract

Objectives: MicroRNAs (miRNAs) play a crucial role in the onset and progress of obesity. The inflammation of adipose tissue is deemed causative of the complications associated with obesity. This study delved into the potential mechanisms of miRNA-mediated SIRT1 regulation and inflammatory factors modulation in 3T3-L1 cells. Methods: 3T3-L1 cells were differentiated into mature and hypertrophied adipocytes and the expression of selected miRNAs was evaluated by real-time PCR. 3T3-L1 cells were transfected with the mimic and inhibitor sequences of miR-186, together with the appropriate controls. Western blot analysis assessed the expression level of SIRT1 protein, and the interaction between miR-186 and SIRT1 was scrutinized through a luciferase reporter gene assay. Results: Across all the mature and hypertrophied cells, the evaluated miRNAs exhibited a significant increase in expression, highlighting their involvement in fat accumulation at a cellular scale. Notably, miR-186-5p displayed the highest expression in differentiated cells and the hypertrophy model. Induction of miR-186 led to attenuation of SIRT1, while its inhibition by miR-186 inhibitor resulted in upregulation of SIRT1 expression. miR-186 caused a remarkable elevation in the expression of inflammatory genes, including IL-6, IL-1β, TNF-α, and MCP-1, indicating a noticeable pattern of relationship between miR-186-induced SIRT-1 inhibition and inflammation. Conclusions: miR-186 emerges as a pivotal factor in amplifying inflammatory cytokines and down-regulates SIRT1, an effect that might highlight the involvement of SIRT1 in the inflammatory responses of adipocytes, as well as underscoring the crucial role of miR-186 in this process. These findings present miR-186 as a promising target for addressing health challenges related to obesity. © The Author(s), under exclusive licence to Tehran University of Medical Sciences 2024.