α-Linolenic Acid-Enriched Cold-Pressed Perilla Oil Suppress High-Fat Diet-Induced Hepatic Steatosis through Amelioration of the ER Stress-Mediated Autophagy

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.

Effects of Mediterranean Diet in Patients with Nonalcoholic Fatty Liver Disease: A Systematic Review, Meta-Analysis, and Meta-Regression Analysis of Randomized Controlled Trials

“…27 Specifically, the consumption of extra virgin olive oil and lower carbohydrate content was shown to reduce hepatic fat content in the PREDIMED (Prevención con Dieta Mediterránea) 26 and CENTRAL (Diet and Body Composition) trials, 13 respectively. The Med-Diet contains high levels of α-linolenic acids and polyphenols, which have been shown to attenuate hepatic steatosis through downregulation of transcription factors implicated in adipogenesis and lipogenesis, including the peroxisome proliferator-activated receptor 28 and the carbohydrate response element binding protein. 29,30 In both meta-analysis and meta-regression analysis, the Med-Diet led to significant reductions in the FLI.…”

Dysbiosis of Fecal Microbiota From Complement 3 Knockout Mice With Constipation Phenotypes Contributes to Development of Defecation Delay

“…After quantification of the RNA concentration, complement DNA (cDNA) was synthesized using a mixture of oligo-dT primer (Thermo Fisher Scientific Inc., MA, United States), dNTP, and reverse transcriptase (Superscript II, Thermo Fisher Scientific Inc.). RT-qPCR was then conducted using a cDNA template and 2 × Power SYBR Green (Toyobo Co., Osaka, Japan), as described in a previous study ( Bae et al, 2020 ). The primer sequences used to evaluate mRNA levels were as follows: AQP3, sense primer 5'-GGTGG TCCTG GTCAT TGGAA-3', antisense primer 5'-AGTCA CGGGC AGGGT TGA-3'; C-kit, sense primer 5'-TGTTG CCTTC ACGGT TTTCC-3', antisense primer 5'-AACGA TCACT TCTTC CAGGT TCA-3'; 5-HT, sense primer 5'-CTGAG GCCCT CCCAC ATCT-3', antisense primer 5'-GGAAA GGAAC AAGGC CAACA-3'; β-actin, sense and antisense primers 5'-ACGGC CAGGT CATCA CTATT G-3' and 5'-CAAGA AGGAA GGCTG GAAAA GA-3', respectively.…”

Metabolomics Profiling of EUS-FNA Sample Predicts Advanced Pancreatic Adenocarcinoma Prognosis

“…Studies already proved the protective effect of α-linolenic acid in several in ammatory conditions, such as ulcerative colitis and hepatic steatosis. (17,18) Meanwhile, epidemiologic evidence on the risk of PAC remains controversial. (19) As a member of n-3 polyunsaturated fatty acids, α-linolenic acid plays a distinctive role of carbon source substitution in athletes' aerobic performance when the carbohydrate reserve is consumed.…”