Phospholipid metabolism was significantly changed in mice fed the HFHCC diet. (A) In the liver, total ceramides (Cer) and sphingomyelins (SM) levels were both significantly elevated after HFHCC diet compared to controls. Total phosphotidylcholines (PC) levels remained unaffected, while total phosphoethanolamines (PE) levels were markedly reduced by 44% after the HFHCC diet compared to controls. Total lysophosphotidylcholines (LPC) levels were increased after HFHCC diet, and total lysophosphoethanolamines (LPE) levels were not significantly different. Hepatic PC/PE ratio was significantly higher in the HFHCC diet group compared to controls. (B) Analysis by constructing heat maps showed metabolite species that were significantly changed in the liver after HFHCC diet. All Cer and SM species, most of which were saturated and monounsaturated, were highly elevated. There was a trend that PC and PE species containing low number (0–3) of double bonds were elevated, while those with higher number (>3) of double bonds, were reduced. (C) In the plasma, total levels of Cer and SM were both significantly elevated in the HFHCC diet group. PC levels were unchanged, while PE levels were significantly increased in the HFHCC diet group compared to control diet group. LPC levels were unchanged, while LPE levels were significantly decreased in the HFHCC diet group compared to control diet group. (D) Analysis by constructing heat maps showed metabolite species that were significantly changed in the plasma after the HFHCC diet. All detected Cer, SM, PC and PE species were elevated, while LPC and LPE species appeared reduced. (*adjusted p < 0.05; n = 6 mice for HFHCC diet, n = 8 for Control diet).