PPARG and obesity due to melanocortin 4 receptor deficiency: Another key mechanism for the alternative activation of tissue macrophages is the peroxisome proliferator activated receptor‐γ (PPARγ) pathway.(67) In animal studies, the disruption of this pathway also was associated with diet‐induced obesity, insulin resistance, and glucose intolerance.(67) PPARγ deficiency can also lead to increased itaconate production, which suggests that itaconate acts as an alternative regulator of M2‐like polarization.(55)