In conclusion, our study highlights the physiological significance of let-7a-5p in lipid accumulation and suggests that the let-7a-5p/Srebf2 and let-7a-5p/Thbs1/PI3K-AKT-mTOR axes may represent potential mechanisms for controlling lipid accumulation in obesity. This evidence concerns the gene SREBF2 and obesity due to melanocortin 4 receptor deficiency.