Excessive
fat deposition is the main character in nonalcoholic
fatty liver disease (NAFLD), while γ-linolenic acid (GLA) is
a polyunsaturated fatty acid that can reduce lipid deposition. This
study investigated the effect and regulatory mechanism of GLA (100
μM) on lipid metabolism in alpha mouse liver 12 (AML-12) cells
treated by 400 μM palmitic acid (PA). GLA reduced lipid content
and increased fatty acid β oxidation, as indicated by decreasing
triglyceride and cholesterol contents and increasing mRNA and protein
expressions of CPT1α and PPARα. GLA relieved oxidative
stress caused by PA, upregulated mRNA levels of superoxide dismutase
and glutathione peroxidase, and decreased reactive oxygen species
content. GLA reduced apoptosis, as indicated by decreases in the BAX/BCL2
expression level and apoptosis percentage. GLA activated autophagy,
autophagosome-lysosome fusion, and LKB1-AMPK-mTOR signaling and upregulated
mRNA and protein expressions of Beclin-1, autophagy-related 5, and
liver kinase B1 (LKB1). These effects of GLA on lipid metabolism disorders
of PA-treated hepatocytes were reversed by autophagy inhibitor 3MA
and AMPK inhibitor compound C, confirming our conclusions. Overall,
GLA can protect AML-12 cells from lipid metabolism disorder caused
by PA via balancing autophagy and apoptosis mediated by the LKB1-AMPK-mTOR
pathway. Consequently, GLA, as a dietary supplement, can help to prevent
and treat NAFLD by regulating lipid metabolism and autophagy.