The combined intervention protocol used in our study was able to reverse obesity-induced insulin resistance and metabolic dysfunction by increasing levels of the anti-inflammatory adipokine CTRP 12/adipolin and its regulatory factor KLF15, while at the same time suppressing furin levels to prevent cleavage of the insulin-sensitizing full form of adipolin. Here, KLF15 is linked to obesity due to melanocortin 4 receptor deficiency.