SIRT1 and obesity due to melanocortin 4 receptor deficiency: Based on these observations, we determined: 1) whether AMPK/SIRT1 not only detects excess unhealthy nutrients (e.g. saturated lipids) associated with obesity, but also responds to healthy nutrients (e.g. ω-3 PUFAs) beneficial for prevention and treatment of obesity-associated metabolic disorders; and 2) whether activation of AMPK/SIRT1 in response to ω-3 PUFAs antagonizes macrophage inflammation via antagonism of NF-κB signaling by deacetylating p65.