• 한국축산식품학회지
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• 제37권6호
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• pp.931-939
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• 2017

Alcoholic liver disease (ALD) is a complex multifaceted disease that involves oxidative stress and inflammation as the key mediators. Despite decades of intensive research, there are no FDA-approved therapies, and/or no effective cure is yet available. Probiotics have received increasing attention in the past few years due to their well-documented gastrointestinal health-promoting effects. Interestingly, emerging studies have suggested that certain probiotics may offer benefits beyond the gut. Lactobacillus fermentum LA12 has been previously demonstrated to play a role in inflammatory-related disease. However, the possible protective effect of L. fermentum LA12 on ALD still remain to be explored. Thus, the aim of this study was to evaluate the possible protective effect of L. fermentum LA12 on alcohol-induced gut barrier dysfunction and liver damage in a rat model of alcoholic steatohepatitis (ASH). Daily oral administration of L. fermentum LA12 in rat model of ASH for four weeks was shown to significantly reduced intestinal nitric oxide production and hyperpermeability. Moreover, small intestinal histological- and qRT-PCR analysis further revealed that L. fermentum LA12 treatment was capable of up-regulating the mRNA expression levels of tight junction proteins, thereby stimulating the restitution of barrier structure and function. Serum and hepatic analyses also revealed that the restoration of epithelial barrier function may prevent the leakage of endotoxin into the blood, subsequently improve liver function and hepatic steatosis in the L. fermentum LA12-treated rats. Altogether, results in this study suggest that L. fermentum LA12 may be used as a dietary adjunct for the prevention and treatment of ASH.

• Natural Product Sciences
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• 제9권1호
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• pp.13-17
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• 2003

The hepatoprotective effect of the ethanolic extract of Coccinia indica fruits in rats treated with carbon tetrachloride. In hepatotoxic rats, liver damage was studied by assessing parameters such as aspartate aminotransferase (AST), alanine aminotransferase (AlT), alkaline phosphatase (AIP) and gamma glutamyl transpeptidase (GGT) in serum, and concentrations of total proteins, total lipids, phospholipids, triglycerides and cholesterol in both serum and liver. The effect of co-administration of ethanolic extract on the above parameters was further investigated. Histopathological study of the liver in experimental animals was also undertaken. Hepatic damage as evidenced by a rise in the levels of AST, AIT, AIP and GGT in serum, and also changes observed in other biochemical parameters In serum and liver showed a tendency to attain near normalcy in animals co-administered with the extract. The normal values for AST (IU/L), AIP (IU/I), protein (g/100 ml) and total lipids (mg/100 ml) in serum (i.e.,20.24, 70.04, 5.72 and 135.54 respectively) were found to alter towards values 32.61, 127.11, 3.83 and 265.91 in hepatotoxic rats. These parameters Attained near normal values (I.e.,22.82, 79.30, 5.22 and 151.24 for AST, AIP protein and total lipids respectively) in ethanolic extract co-administered rats. Profound steatosis, ballooning degeneration and nodule formation observed in the hepatic architecture of $CCl_4$ treated rats were found to acquire near-normalcy in drug co-administered rats, thus corroborating the biochemical observations. Thus the study substantiates the hepatoprotective potential of ethanolic extract of Coccinia indica fruits.

• Nutrition Research and Practice
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• 제7권4호
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• pp.267-272
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• 2013

The anti-obesity effects of a hot water extract from wasabi (Wasabia japonica Matsum.) leaves (WLE), without its specific pungent constituents, such as allyl-isothiocyanate, were investigated in high fat-diet induced mice. C57J/BL mice were fed a high-fat diet (control group) or a high-fat diet supplemented with 5% WLE (WLE group). Physical parameters and blood profiles were determined. Gene expression associated with lipid metabolism in liver and white adipose tissue were analyzed. After 120 days of feeding, significantly lower body weight gain, liver weight and epididymal white adipose tissue weight was observed in the WLE group compared to the control group. In liver gene expression within the WLE group, PPAR${\alpha}$ was significantly enhanced and SREBP-1c was significantly suppressed. Subsequent downstream genes controlled by these regulators were significantly suppressed. In epididymal white adipose tissue of the WLE group, expression of leptin, PPAR${\gamma}$, and C/EBP${\alpha}$ were significantly suppressed and adiponectin was significantly enhanced. Acox, related to fatty acid oxidization in adipocytes, was also enhanced. Our results demonstrate that the WLE dietary supplement induces mild suppression of obesity in a high-fat diet induced mice, possibly due to suppression of lipid accumulation in liver and white adipose tissue.

• 대한한방내과학회지
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• 제44권2호
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• pp.138-145
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• 2023

Objective: This study identified the effects of Korean medicine treatment on a patient with metabolic dysfunction-associated fatty liver disease (MAFLD). Methods: A 43-year-old man with MAFLD was treated with Saenggangunbi-tang with regular exercise from August 13, 2022, to December 24, 2022, to reduce fatigue and dyspepsia and to improve laboratory findings, such as liver enzymes and lipid profiles. We observed changes in symptoms and laboratory findings during the approximately four-month treatment. Results: Treatment with Saenggangunbi-tang resulted in decreased serum levels of liver enzymes, triglycerides, hepatic steatosis index scores, and clinical symptoms. During the treatment, the patient performed regular exercise; however, there was no significant change in body weight until the end of the study. Conclusion: This study suggests the availability of Saenggangunbi-tang as a therapeutic option for managing MAFLD patients.

• Biomolecules & Therapeutics
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• 제32권1호
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• pp.94-103
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• 2024

Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive accumulation of fat in the liver, and there is a global increase in its incidence owing to changes in lifestyle and diet. Recent findings suggest that p53 is involved in the development of non-alcoholic fatty liver disease; however, the association between p53 expression and the disease remains unclear. Doxorubicin, an anticancer agent, increases the expression of p53. Therefore, this study aimed to investigate the role of doxorubicin-induced p53 upregulation in free fatty acid (FFA)-induced intracellular lipid accumulation. HepG2 cells were pretreated with 0.5 ㎍/mL of doxorubicin for 12 h, followed by treatment with FFA (0.5 mM) for 24 h to induce steatosis. Doxorubicin pretreatment upregulated p53 expression and downregulated the expression of endoplasmic reticulum stress- and lipid synthesis-associated genes in the FFA -treated HepG2 cells. Additionally, doxorubicin treatment upregulated the expression of AMP-activated protein kinase, a key modulator of lipid metabolism. Notably, siRNA-targeted p53 knockdown reversed the effects of doxorubicin in HepG2 cells. Moreover, doxorubicin treatment suppressed FFA -induced lipid accumulation in HepG2 spheroids. Conclusively, these results suggest that doxorubicin possesses potential application for the regulation of lipid metabolism by enhance the expression of p53 an in vitro NAFLD model.

• Journal of Microbiology and Biotechnology
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• 제23권11호
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• pp.1569-1576
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• 2013

In mice, supplementation of t10,c12 conjugated linoleic acid (CLA) increases liver mass and hepatic steatosis via increasing uptake of fatty acids released from adipose tissues. However, the effects of t10,c12 CLA on hepatic lipid synthesis and the associated mechanisms are largely unknown. Thus, we tested the hypothesis that gut microbiota-producing t10,c12 CLA would induce de novo lipogenesis and triglyceride (TG) synthesis in HepG2 cells, promoting lipid accumulation. It was found that treatment with t10,c12 CLA ($100{\mu}M$) for 72 h increased neutral lipid accumulation via enhanced incorporation of acetate, palmitate, oleate, and 2-deoxyglucose into TG. Furthermore, treatment with t10,c12 CLA led to increased mRNA expression and protein levels of lipogenic genes including SREBP1, ACC1, FASN, ELOVL6, GPAT1, and DGAT1, presenting potential mechanisms by which CLA may increase lipid deposition. Most strikingly, t10,c12 CLA treatment for 3 h increased phosphorylation of mTOR, S6K, and S6. Taken together, gut microbiota-producing t10,c12 CLA activates hepatic de novo lipogenesis and TG synthesis through activation of the mTOR/SREBP1 pathway, with consequent lipid accumulation in HepG2 cells.

• Biomolecules & Therapeutics
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• 제29권4호
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• pp.419-426
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• 2021

In this study, we aimed to investigate the effects of 8 weeks of treatment with a combination of evogliptin and leucine, a branched-chain amino acid, in mice with high-fat diet (HFD)-induced diabetes. Treatment with evogliptin alone or in combination with leucine reduced the body weight of the mice, compared to the case for those from the HFD control group. Long-term treatment with evogliptin alone or in combination with leucine resulted in a significant reduction in glucose intolerance; however, leucine alone did not affect postprandial glucose control, compared to the case for the mice from the HFD control group. Furthermore, the combination of evogliptin and leucine prevented HFD-induced insulin resistance, which was associated with improved homeostasis model assessment for insulin resistance, accompanied by markedly reduced liver fat deposition, hepatic triglyceride content, and plasma alanine aminotransferase levels. The combination of evogliptin and leucine increased the gene expression levels of hepatic peroxisome proliferator-activated receptor alpha, whereas those of the sterol regulatory element-binding protein 1 and stearoyl-CoA desaturase 1 were not altered, compared to the case in the HFD-fed mice (p<0.05). Thus, our results suggest that the combination of evogliptin and leucine may be beneficial for treating patients with type 2 diabetes and hepatic steatosis; however, further studies are needed to delineate the molecular mechanisms underlying the action of this combination.

• 한국환경성돌연변이발암원학회:학술대회논문집
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• 한국환경성돌연변이발암원학회 2004년도 KSOT/KEMS Fall Annual Meeting
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• pp.134-134
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• 2004

• BMB Reports
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• 제50권7호
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• pp.367-372
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• 2017

Monoacylglycerol acyltransferase 1 (MGAT) is a microsomal enzyme that catalyzes the synthesis of diacylglycerol (DAG) and triacylglycerol (TAG). However, the subcellular localization and catalytic function domain of this enzyme is poorly understood. In this report, we identified that murine MGAT1 localizes to the endoplasmic reticulum (ER) under normal conditions, whereas MGAT1 co-localize to the lipid droplets (LD) under conditions of enriching fatty acids, contributing to TAG synthesis and LD expansion. For the enzyme activity, both the N-terminal transmembrane domain and catalytic HPHG motif are required. We also show that the transmembrane domain of MGAT1 consists of two hydrophobic regions in the N-terminus, and the consensus sequence FLXLXXXn, a putative neutral lipid-binding domain, exists in the first transmembrane domain. Finally, MGAT1 interacts with DGAT2, which serves to synergistically increase the TAG biosynthesis and LD expansion, leading to enhancement of lipid accumulation in the liver and fat.

• Journal of Ginseng Research
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• 제38권3호
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• pp.167-172
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• 2014

Background: Roles of immune reaction and toll-like receptor-4 (TLR-4) have widely been established in the pathogenesis of alcoholic liver disease (ALD). Methods: We evaluated the biologic efficacy of Korean Red Ginseng (KRG), urushiol, and probiotics (Lactobacillus rhamnosus R0011 and Lactobacillus acidophilus R0052) in mouse models of ALD. Sixty C57BL/6 mice were equally divided into six feeding groups for 10 weeks: normal diet, alcohol, control, alcohol + KRG, alcohol + urushiol, and alcohol + probiotics. Alcohol was administered via a LiebereDeCarli liquid diet containing 10% alcohol. TLR-4 expression, proinflammatory cytokines, and histology, as well as the results of liver function tests were evaluated and compared. Results: No between-group differences were observed with regard to liver function. TLR-4 levels were significantly lower in the KRG, urushiol, and probiotics groups than in the alcohol group ($0.37{\pm}0.06ng/mL$, $0.39{\pm}0.12ng/mL$, and $0.33{\pm}0.07ng/mL$, respectively, vs. $0.88{\pm}0.31ng/mL$; p < 0.05). Interleukin-$1{\beta}$ levels in liver tissues were decreased among the probiotics and KRG groups. The tumor necrosis factor-${\alpha}$ level of liver tissue was decreased in the KRG group. Conclusion: The pathological findings showed that alcohol-induced steatosis was significantly reduced by KRG and urushiol. As these agents improve immunologic capacity, they may be considered in potential anti-ALD treatments.