Elevated CYP2E1 is a marker for increased oxidative stress and is involved in the biotransformation of many small molecular weight xenobiotics and endogenous substrates such as fatty acids [7–9]. Furthermore, its activity and protein increased in response to HFD [7,10,11,17]. Thus, we evaluated whether HFD increased the activity of CYP2E1 in the four mouse groups. Indeed, both CYP2E1 activity and protein levels were significantly increased in the WT-HFD group compared to its corresponding LFD-fed group, while CYP2E1 was not detectable in Cyp2e1-null mice (Figs. 2A and B). p38 was used as a loading control since we observed that the levels of β-actin, glyceraldehyde 3-phosphate dehydrogenase, and tubulin are all fluctuated in response to the HFD (not shown). Staining with Coomassie blue also verified similar protein loading for all samples (not shown).