Collectively, our data suggest that under conditions where MBOAT7 activity is suppressed (obesity or with the rs641738 variant) inefficient acylation of LPI substrate allows for these lipids to accumulate and initiate autocrine, paracrine, and potentially endocrine signaling that impact the progression of NAFLD and insulin resistance. The gene discussed is MBOAT7; the disease is obesity due to melanocortin 4 receptor deficiency.