In summary, our results support a proposed functional model: adipose tissue Nrf2 deficiency may alleviate obesity-associated inflammation by mitigating oxidative stress, improving mitochondrial function, and maintaining membrane integrity, thereby potentially reducing mtDNA leakage into the cytoplasm and ultimately suppressing the cGAS-STING pathway. This evidence concerns the gene STING1 and obesity due to melanocortin 4 receptor deficiency.