In addition to nutrient surplus, the initiation of metabolic disease is also associated with mitochondrial dysfunction.26 NLRP3 is a proposed sensor for mitochondrial damage and dysfunction through direct interaction with mitochondrial DNA and cardiolipin, or indirectly, through sensing reactive oxygen species generated by dysfunctional mitochondria.11 In keeping with a disease-driving role for NLRP3 activated by nutrient excess and mitochondrial dysfunction, Nlrp3-deficient mice appear to be resistant to several metabolic diseases. The gene discussed is NLRP3; the disease is metabolic disease.