High Fat Diet Rich in Linoleic Acid Oil Increases Linoleate-Rich Cardiolipin Species in C57BL6/J Mice

Objectives Dietary fat quality alters the fatty acid composition of phospholipids in cell membranes. The fatty acid composition of the inner mitochondrial membrane phospholipid cardiolipin (CL) impacts mitochondria function where linoleic acid (LA) -rich cardiolipin, e.g., tetralinoleoyl-cardiolipin (L4CL). This study compared the effects of a LA-rich diet and a saturated fat (SF)-rich diet on L4CL in the liver of mice. Methods Male C57BL6/J mice (9 weeks, N = 24) randomized by body weight to a high fat diet (24% fat w/w) containing LA-rich safflower oil (SO) or SF-rich oil (LD) for 18 weeks. Food intake and body weight were measured every two days. Fasting blood glucose and body composition (Echo/MRI) were measured in the washout period and again 11 weeks later. Insulin tolerance test (ITT) measured insulin sensitivity on day 85, and mice were euthanized starting after day 100. Liver cardiolipin speciation was measured using HPLC/MS. A two-sample t-test at a 5% significance level was used to determine differences between diet groups. Results Body weight, cumulative food intake, adipose and lean tissues were not significantly different between diet groups at Day 130. Fasting glucose between diets was not significantly different at any timepoints throughout the study. Blood glucose during the ITT was significantly different between LA-rich and SF-rich diets for the last two time points, 90 minute and 120 minute. The SO diet increased hepatic L4CL (% of total CL) compared to the LD diet (P-value: < 0.01). Conclusions Hepatic CL fatty acid composition reflected dietary fat composition. Feeding of a high fat LA-rich diet increased hepatic L4CL species and hastened resolution of glucose levels in response to insulin in the SO diet group (vs. LD diet group). Funding Sources Supported by Human Nutrition - Human Sciences, Carol S. Kennedy endowment, OADRC.