To reveal whether a long-term HFD alters gene expression levels in the retina, we used 4D-label free mass spectrometry to quantify proteins in the whole retinas of HFM and age-mated NM. As the liver plays a crucial role in metabolism of the whole body, HFD has a huge impact on gene expression in the liver. To compare the similarities and differences in the effects of a HFD on retinal and hepatic gene regulatory networks, we also performed proteomic analyses on the livers from HFM and NM.