In summary, we show that lowering apoCIII reduces the expression of inflammatory cytokines and counteracts the negative metabolic effects of HFD-induced obesity in both SAT and VAT and, together with our previous results in liver and BAT, we entertain the possibility that this can be implemented as a treatment strategy for obesity and insulin resistance. Here, APOC3 is linked to obesity due to melanocortin 4 receptor deficiency.