JNK and IKKβ are activated by inflammatory stimuli, such as tumor necrosis factor alpha (TNF-α), contributing to insulin resistance in obesity, while conventional and novel PKC isoforms are activated via their recruitment to the plasma membrane by diacylglycerol, accumulated into the cells as a consequence of the increased availability of free fatty acids. Here, TNF is linked to obesity due to melanocortin 4 receptor deficiency.