γ-Linolenic Acid Prevents Lipid Metabolism Disorder in Palmitic Acid-Treated Alpha Mouse Liver-12 Cells by Balancing Autophagy and Apoptosis via the LKB1-AMPK-mTOR Pathway

Abstract

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.

2-Amino-3-Methylimidazo[4,5-f]quinoline Triggering Liver Damage by Inhibiting Autophagy and Inducing Endoplasmic Reticulum Stress in Zebrafish (Danio rerio)

“…In addition, accumulating evidence show that autophagy and apoptosis may share common signaling mechanisms and occur simultaneously in hepatocytes [46][47][48]. Therefore, it is particularly important to explore the relationship among ERS, autophagy, and apoptosis, which may be the potential mechanism of IQ-induced liver damage.…”

Research Progress of Rhubarb in the Treatment of Liver Fibrosis

“…The organic acids contained in rhubarb mainly include palmitic acid, linoleic acid, etc.Palmitic acid is a saturated fatty acid, which is of great significance for the pathogenesis of lipid metabolism-related diseases.Abnormally increased lipids in liver tissue can promote liver fibrosis by affecting lipid metabolism balance and enhancing lipid peroxidation,at the same time, hepatic stellate cell activation is also closely related to lipid metabolism.When the liver is injured, the phenotype and function of hepatic stellate cells change, they can secrete a variety of cytokines to promote their own activation [6], and the vitamin A lipid droplets they contain are gradually lost [7].Palmitic acid can participate in vitamin A metabolism and affect the biological activity of hepatic stellate cells.Abergel [8] found that adding palmitic acid (75uM) and normal dose of vitamin A to the culture medium of hepatic stellate cell line (PAV-1) can increase the number of lipid droplets in PAV-1 cells, significantly inhibit cell proliferation and α-SMA , and significantly reduced the level of collagen I, indicating that palmitic acid can induce the transformation of hepatic stellate cells from activation to quiescence.Linolenic acid is a polyunsaturated fatty acid that reduces lipid deposition and also plays an important role in regulating lipid metabolism [9].…”

Hotspots and trends in liver kinase B1 research: A bibliometric analysis

“…LKB1 also can inhibit cell growth through suppressing the anti-apoptotic factors, such as STAT3, JNK, KRAS, MAPK, cyclooxygenase-2, and c-myc [42,59,60]. In recent studies, LKB1-AMPK is still the major signaling pathway to regulate cell apoptosis [61][62][63]. The role of LKB1 plays in epithelial polarity is associated with MARK/PAR1 and AMPK.…”