Phosphatidylcholine (PC) is the major component of cell membranes and is synthesized de novo in the Kennedy pathway and then undergoes extensive deacylation-reacylation remodeling via Lands' cycle (non- Kennedy pathway). The reacylation is catalyzed by lysophosphatidylcholine acyltransferase (LPCAT), which adds a polyunsaturated fatty acid at the sn-2 position. Polyunsaturated PC content influences plasma membrane structure and function. Four LPCAT isoforms have been described to date, and we determined that LPCAT3 is the major isoform in macrophages and adipocytes. Here, we hypothesize that an increase in saturated PCs in the plasma membrane of macrophages, as a consequence of Lpcat3 deficiency, promotes inflammation by activating NF?B and MAP kinase signaling and promotes inflammation-induced systemic insulin resistance and atherosclerosis (Aims 1 and 2). Lpcat3 deficiency in adipocytes might blunt insulin signaling, thereby accelerating inflammation, systemic insulin resistance and atherosclerosis (Aim 3). Lpcat3 overexpression should have the opposite effects. The outcomes of this study could lead to a novel anti- atherogenic strategy for clinical use.