Abstract
Perilla oil has been considered to have excellent potential for treating various diseases due to its contents of beneficial fatty acids, such as α-linolenic acid, oleic acid and linoleic acid. The therapeutic effects and molecular mechanism of an α-linolenic acid-enriched cold-pressed perilla oil (LEP) on hepatic steatosis of an obesity model were investigated by analyzing alterations in fat accumulation and endoplasmic reticulum (ER) stress-mediated autophagy, in high-fat diet (HFD)-induced obesity C57BL/6N mice treated with LEP for 16 weeks. Although no significant alterations were detected in body weight and most organ weights, the liver weight and accumulation of lipid droplets in the liver section were significantly lower in HFD + LEP treated group as compared to the HFD + Vehicle treated group. Reduced mRNA expression levels of adipogenesis and lipogenesis regulating factors, including the peroxisome proliferator-activated receptor (PPAR)γ, CCAAT/enhancer-binding protein (C/EBP)α, fatty acid synthase (FAS), and adipocyte fatty acid-binding protein 2 (aP2) were observed after LEP treatment for 16 weeks, while the levels of lipolysis were remarkably increased in the same group. Moreover, the LEP-treated groups showed suppression of ER stress-regulating factors, such as the C/EBP homologous protein (CHOP), eukaryotic translation initiation factor 2α (eIF2α), inositol-requiring protein 1 (IRE1)α, and Jun-N-terminal kinase (JNK) during anti-hepatic steatosis effects. The expression level of the microtubule-associated protein 1A/1B-light chain 3 (LC3) protein and phosphatidylinositol-3-kinase (PI3K)/AKT/ mammalian target of rapamycin (mTOR) pathway for the autophagy response showed a significant decrease in the HFD+LEP-treated group. Furthermore, ER stress-mediated autophagy was accompanied with enhanced phosphorylation of extracellular signal-regulated kinase (ERK), JNK, and p38 protein in the mitogen-activated protein (MAP) kinase signaling pathway. Taken together, the results of the present study indicate that treatment with LEP inhibits hepatic steatosis in the HFD-induced obese model through regulation of adipogenesis and lipolysis. We believe our results are the first to show that the anti-hepatic steatosis activity of α-linolenic acid from cold-pressed perilla oil might be tightly correlated with the amelioration of ER stress-mediated autophagy.
Highlights
One of nonalcoholic fatty liver disease (NAFLD) is accompanied by intracellular accumulation of lipid droplets in the liver as hepatic steatosis [1]
(4.95%), and stearic acid acid (2.35%) (Figure 1A). These results indicate the potential of linolenic acid-enriched cold-pressed perilla oil (LEP) for treating high-fat diet (HFD)-induced. These results indicate the potential of LEP for treating HFD-induced hepatic steatosis
The current study investigates the molecular mechanism of endoplasmic reticulum (ER) stress-mediated autophagy based onthe the molecular mechanism of stress-mediated autophagy based on the inhibitory effect exerted by for inhibitory effect exerted by LEP for hepatic steatosis
Summary
One of nonalcoholic fatty liver disease (NAFLD) is accompanied by intracellular accumulation of lipid droplets in the liver as hepatic steatosis [1]. Several previous studies on steatosis in the liver tissue of NAFLD, genetic, and diet-induced obesity (DIO) models show scientific evidence correlating hepatic steatosis and ER stress [5,6]. Autophagy is a well-known lysosomal degradative pathway that stimulates cell survival through the regulation of energy supplements or defective organelle elimination during injury conditions [12]. This pathway is linked to the reduction of intracellular lipid droplets, attenuation of inflammation, and improvement of hepatic injury in NAFLD [13]. The role and mechanism of ER stress-mediated autophagy in hepatic steatosis remains unclear, many studies have shown evidence for the interplay between ER stress and inflammation in the pathogenesis of hepatic steatosis [14,15]
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