Plasma Linoleic Acid Is Related to Lower Hepatic Steatosis Index and Higher Linoleate-Rich Cardiolipin in Adults with MAFLD

Linoleic acid (LA: 18:2n-6) is a required nutrient that supports mitochondrial function as a component of the inner mitochondrial membrane, cardiolipin (CL). Tetralinoleoyl CL (LA4CL) supports optimal fatty acid oxidation, which is impaired in the liver in adults with MAFLD. Data were analyzed from 74 adults with MAFLD recruited from the Columbus region, Ohio, United States. Fatty acid content and CL species were measured in blood and peripheral blood mononuclear cells (PBMCs). Liver fat was assessed using magnetic resonance imaging-proton density fat fraction (MRI-PDFF), and liver stiffness using magnetic resonance elastography (MRE). Although plasma LA was not significantly associated with liver fat or stiffness, there was a borderline inverse association with liver fat in females (p = 0.091). Plasma LA was negatively associated with hepatic steatosis index (HSI) (p = 0.014) and homeostatic model assessment for insulin resistance (HOMA-IR) (p = 0.05). Plasma LA was positively correlated with LA4CL in PBMC expressed as a % of total cardiolipin (r = 0.501, p < 0.001) and of 72-C CL (r = 0.535, p < 0.001). Borderline inverse relationships with liver fat were observed for LA4CL expressed as % of 72-C CL (p = 0.074) and % of total CL (p = 0.063). LA4CL (% of 72-C CL) was positively associated with HOMA-IR in men (p = 0.006) but not women. Plasma LA was inversely associated with the presence of T2DM (OR= 0.831, 95% CI: 0.711, 0.955, p = 0.013). Mediation analysis indicated that HOMA-IR accounted for ~25.2% of this relationship.