PNPLA3 and fatty liver disease: To determine if LD targeting of hPNPLA3 I148M is required for the liver steatosis, we utilized PNPLA3-KO mice and re-expressed WT hPNPLA3, hPNPLA3 I148M, I148MAAEE, or GFP control specifically in the liver of mice and challenged them with a diet high in sucrose to induce liver steatosis (33).