Using a murine model of NASH, we show that increased circulatory Lcn2 upregulates expression of Lcn2 receptor (24p3R) on brain cells and secretion of a damage associated molecular pattern protein (DAMP), a high mobility group box 1 (HMGB1) that subsequently induces oxidative stress and nod-like receptor protein 3 (NLRP3) inflammasome activation on brain cells. The gene discussed is SLC22A17; the disease is metabolic dysfunction-associated steatohepatitis.