Increases in traditional serum
lipid profiles are associated with
obesity,
cancer, and
cardiovascular disease. Recent lipidomic analysis has indicated changes in serum lipidome profiles, especially in regard to specific
phosphatidylcholines, associated with
obesity. However, little work has evaluated murine hepatic liver lipidomic profiles nor compared these profiles across age, high-fat diet, or specific genotypes, in this case the lack of hepatic Cyp2b
enzymes. In this study, the effects of age (9 months old), high-fat diet (4.5 months old), and the loss of three primarily hepatic xeno- and endobiotic metabolizing
cytochrome P450 (Cyp)
enzymes, Cyp2b9, Cyp2b10, and Cyp2b13 (Cyp2b-null mice), on the male murine hepatic lipidome were compared. Hierarchical clustering and principal component analysis show that age perturbs hepatic
phospholipid profiles and serum
lipid markers the most compared to young mice, followed by a high-fat diet and then loss of Cyp2b. Several
lipid biomarkers such as PC/PE ratios, PE 38 : 6, and LPC concentrations indicate greater potential for
NAFLD and
hypertension with mixed effects in Cyp2b-null mice(less
NAFLD and greater
hypertension-associated markers).
Lipid profiles from older mice contain greater total and
n-6 fatty acids than normal diet (ND)-fed young mice; however, surprisingly, young Cyp2b-null mice contain high n-6 : n-3 ratios. Overall, the lack of Cyp2b typically enhanced adverse physiological parameters observed in the older (9 mo) mice with increased
weight gain combined with a deteriorating
cholesterol profile, but not necessarily all
phospholipid profiles were adversely perturbed.