INS and obesity due to melanocortin 4 receptor deficiency: Since CB2 regulates immune response, the earliest study relating CB2 and obesity disorders demonstrated that CB2 activation using the agonist JWH-133 in HFD-fed mice potentiated obesity-associated inflammation, insulin resistance, and non-alcoholic fatty acid disease [140], while treatment of WT mice with the CB2 antagonist SR 144,528 resulted in improved insulin sensitivity [35].