Plasma linoleic acid is related to lower hepatic steatosis index and higher linoleate-rich cardiolipin in adults with MAFLD.

Linoleic acid (LA, C18:2n-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 metabolic dysfunction-associated fatty liver disease (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, and liver stiffness was assessed using magnetic resonance elastography. 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 (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 percentage of total cardiolipin (r = 0.501, P < 0.001) and 72-C CL (r = 0.535, P < 0.001). Borderline inverse relationships with liver fat were observed for LA4CL expressed as a percentage of 72-C CL (P = 0.074) and 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 type 2 diabetes mellitus (odds ratio = 0.831, 95% confidence interval = 0.711, 0.955, P = 0.013). Mediation analysis indicated that HOMA-IR accounted for ∼25.2% of this relationship.NEW & NOTEWORTHY Remodeling of cardiolipin (CL) is altered in the peripheral blood mononuclear cells (PBMCs) of individuals with metabolic dysfunction-associated fatty liver disease (MAFLD), with reduced linoleic acid (LA). Whether specific CL species, such as LA4CL in PBMCs, or circulating LA levels relate to liver stiffness or hepatic fat is unknown. This study identifies both global- and sex-specific associations between plasma LA, PBMC-derived LA4CL, hepatic fat, liver stiffness, and type 2 diabetes mellitus in adults with MAFLD.