BACKGROUND : Hepatic mitochondrial dysfunction has been found to be a major cause of fat accumulation in the liver and individuals with fatty liver conditions have hepatic mitochondrial structural abnormalities and a switch in the side chain composition of the mitochondrial phospholipid, cardiolipin, from poly- to monounsaturated fatty acids. Linoleic acid (LA), an essential dietary fatty acid, has been shown to remodel nascent cardiolipin to its tetralinoleoylcardiolipin (L4CL, cardiolipin with four LA side chains) form which is integral for mitochondrial membrane structure and function to promote fatty acid oxidation. It is unknown, however, whether increasing LA in the diet can increase hepatic L4CL levels, improve mitochondrial respiration compared to a diet rich in monounsaturated and saturated fatty acids.

OBJECTIVES : The main aim of this study was to test the ability of a diet fortified with LA-rich safflower oil (SO), vs. one fortified with lard (LD), to change levels of L4CL and mitochondrial respiration in the livers of mice.

METHODS : Twenty-four (9-week-old) C57 BL/J6 male mice were fed either the (SO) or (LD) diets for ∼ 100 days while food intake and body weight, fasting glucose and glucose tolerance tests were performed to determine any changes in glycemic control.

RESULTS : Livers from mice fed SO diet had higher relative levels of hepatic L4CL species compared to LD diet-fed mice (p-value: 0.004). Uncoupled mitochondria of mice fed the SO diet, vs. LD diet, had an increased baseline oxygen consumption rate (OCR) and succinate driven respiration (p-values:0.03 & 0.01). SO diet fed mice had increased LA content in all phospholipid classes compared to LD fed mice (p-values: <0.05).

CONCLUSIONS : Our findings reveal that maintaining or increasing hepatic L4CL may result in increased OCR in uncoupled hepatic mitochondria in healthy mice whereas higher OA content of CL reduced mitochondrial function shown by lower OCR in uncoupled mitochondria.