• Journal of Ginseng Research
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• v.34 no.4
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• pp.369-375
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• 2010

This study evaluated the protective effects of ginseng leaf extract (GLE) against high fat-diet-induced hyperglycemia and hyperlipidemia, and explored the potential mechanism underlying these effects in C57BL/6J mice. The mice were randomly divided into four groups: normal control, high fat diet control (HFD), GLE-treated at 250 mg/kg, and GLE-treated at 500 mg/kg. To induce hyperglycemic and hyperlipidemic states, mice were fed a high fat diet for 6 weeks and then administered GLE once daily for 8 weeks. At the end of the treatment, we examined the effects of GLE on plasma glucose, lipid levels, and the expression of genes related to lipogenesis, lipolysis, and gluconeogenesis. Both GLE groups lowered levels of plasma glucose, insulin, triglycerides, total cholesterol, and non-esterified fatty acids when compared to those in HFD group. Histological analysis revealed significantly fewer lipid droplets in the livers of GLE-treated mice compared with HFD mice. To elucidate the mechanism, Western blots and RT-PCR were performed using liver tissue. Compared with HFD mice, GLE-treated mice showed higher levels of phosphorylation of AMP-activated protein kinase (AMPK) and its substrate, acetyl-CoA carboxylase, but no differences in the expression of lipogenic genes such as sterol regulatory element-binding protein 1a, fatty acid synthase, sterol-CoA desaturase 1 and glycerol-3-phosphate acyltransferase. However, the expression levels of lipolysis and fatty acid uptake genes such as peroxisome proliferator-activated receptor-$\alpha$ and CD36 were increased. In addition, phosphoenolpyruvate carboxykinase gene expression was decreased. These results suggest that GLE ameliorates hyperglycemia and hyperlipidemia by inhibiting gluconeogenesis and stimulating lipolysis, respectively, via AMPK activation.

• Animal Bioscience
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• v.35 no.1
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• pp.22-28
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• 2022

Objective: Endoplasmic reticulum (ER) stress engages the unfolded protein response (UPR) that serves as an important mechanism for modulating hepatic fatty acid oxidation and lipogenesis. Chronic fasting in mice induced the UPR activation to regulate lipid metabolism. However, there is no direct evidence of whether negative energy balance (NEB) induces ER stress in the liver of cows. This study aimed to elucidate the relationship between the NEB attributed to feed deprivation and ER stress in bovine hepatocytes. Methods: Blood samples and liver biopsy tissues were collected from 6 non-lactating cows before and after their starvation for 48 h. The blood non-esterified fatty acids (NEFA), β-hydroxybutyric acid (BHBA) and glucose level were analyzed. Real-time quantitative polymerase chain reaction and Western blotting were used to explore the regulation of genes associated with UPR and lipid metabolism. Results: The starvation increased the plasma BHBA and NEFA levels and decreased the glucose level. Additionally, the starvation caused significant increases in the mRNA expression level of spliced X-box binding protein 1 (XBP1s) and the protein level of phosphorylated inositol-requiring kinase 1 alpha (p-IRE1α; an upstream protein of XBP1) in the liver. The mRNA expression levels of peroxisome proliferator-activated receptor alpha and its target fatty acid oxidation- and ketogenesis-related genes were significantly upregulated by the starvation-mediated NEB. Furthermore, we found that the mRNA expression levels of lipogenic genes were not significantly changed after starvation. Conclusion: These findings suggest that in the initial stage of NEB in dairy cows, the liver coordinates an adaptive response by activating the IRE1 arm of the UPR to enhance ketogenesis, thereby avoiding a fatty liver status.

• BMB Reports
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• v.51 no.9
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• pp.462-467
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• 2018

A previous study of ours indicated that Drosophila flightless-1 controls lipid metabolism, and that there is an accumulation of triglycerides in flightless-1 (fliI)-mutant flies, where this mutation triggers metabolic stress and an obesity phenotype. Here, with the aim of characterizing the function of FliI in metabolism, we analyzed the levels of gene expression and metabolites in fliI-mutant flies. The levels of enzymes related to glycolysis, lipogenesis, and the pentose phosphate pathway increased in fliI mutants; this result is consistent with the levels of metabolites corresponding to a metabolic pathway. Moreover, high-throughput RNA sequencing revealed that Drosophila FliI regulates the expression of genes related to biological processes such as chromosome organization, carbohydrate metabolism, and immune reactions. These results showed that Drosophila FliI regulates the expression of metabolic genes, and that dysregulation of the transcription controlled by FliI gives rise to metabolic stress and problems in the development and physiology of Drosophila.

• Biomolecules & Therapeutics
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• v.24 no.6
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• pp.650-658
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• 2016

Chronic alcohol consumption causes alcoholic liver disease, which is associated with the initiation of dysregulated lipid metabolism. Recent evidences suggest that dysregulated cholesterol metabolism plays an important role in the pathogenesis of alcoholic fatty liver disease. Ecklonia stolonifera (ES), a perennial brown marine alga that belongs to the family Laminariaceae, is rich in phlorotannins. Many studies have indicated that ES has extensive pharmacological effects, such as antioxidative, hepatoprotective, and antiinflammatory effects. However, only a few studies have investigated the protective effect of ES in alcoholic fatty liver. Male Sprague-Dawley rats were randomly divided into normal diet (ND) (fed a normal diet for 10 weeks) and ethanol diet (ED) groups. Rats in the ED group were fed a Lieber-DeCarli liquid diet (containing 5% ethanol) for 10 weeks and administered ES extract (50, 100, or 200 mg/kg/day), silymarin (100 mg/kg/day), or no treatment for 4 weeks. Each treatment group comprised of eight rats. The supplementation with ES resulted in decreased serum levels of triglycerides (TGs), total cholesterol, alanine aminotransferase, and aspartate aminotransferase. In addition, there were decreases in hepatic lipid and malondialdehyde levels. Changes in liver histology, as analyzed by Oil Red O staining, showed that the ES treatment suppressed adipogenesis. In addition, the ES treatment increased the expression of fatty acid oxidation-related genes (e.g., PPAR-${\alpha}$ and CPT-1) but decreased the expression of SREBP 1, which is a TG synthesis-related gene. These results suggest that ES extract may be useful in preventing fatty acid oxidation and reducing lipogenesis in ethanol-induced fatty liver.

• Nutrition Research and Practice
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• v.16 no.3
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• pp.314-329
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• 2022

BACKGROUND/OBJECTIVES: Oocyte lipid droplets play a crucial role in meiosis and embryo development. Biotin is associated with fatty acid synthesis and is the coenzyme for acetyl-CoA carboxylase (ACC). The effects of a biotin deficiency on the oocyte lipid metabolism remain unknown. This study examined the effects of a biotin deficiency and its replenishment on murine 1) oocyte lipid droplet levels, 2) ovary lipid metabolism, and 3) oocyte meiosis. MATERIALS/METHODS: Mice were divided into 3 groups: control, biotin deficient (BD), and recovery groups. The control and BD groups were fed a control diet or BD diet (0.004 or 0 g biotin/kg), respectively. The recovery group mice were fed a BD diet until day 21, and were then fed the control diet from days 22 to 64. This study then quantified the oocyte lipid droplet levels, assessed the oocyte mitochondrial function, and examined the ability of oocytes to undergo meiosis. Ovarian phosphorylated ACC (p-ACC), lipogenesis, β-oxidation, and ATP production-related genes were evaluated. RESULTS: The BD group showed a decrease in lipid droplets and mitochondrial membrane potential and increased p-ACC levels. In the recovery group, the hepatic biotin concentration, ovarian p-ACC levels, and mitochondrial membrane potential were restored to the control group levels. On the other hand, the quantity of lipid droplets in the recovery group was not restored to the control levels. Furthermore, the percentage of oocytes with meiotic abnormalities was higher in the recovery group than in the control group. CONCLUSIONS: A biotin deficiency reduced the oocyte lipid droplet levels by downregulating lipogenesis. The decreased lipid droplets and increased oocyte meiosis failure were not fully restored, even though the biotin nutrition status and gene expression of lipid metabolism was resumed. These results suggest that a biotin deficiency remains robust and can be long-lasting. Biotin might play a crucial role in maintaining the oocyte quality.

• Journal of Life Science
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• v.34 no.1
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• pp.1-8
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• 2024

Brain-type natriuretic peptide (BNP) is a cardiac hormone that exerts cardiovascular and renal effects and regulates metabolic processes. In the current study, to determine the hepatic effects of BNP, we investigated whether it improves high-fat diet (HFD)-induced hepatic IR and characterized its possible mechanism. No significant differences in body weight, fat mass, or lean mass were observed between the saline- and BNP-treated groups of normal diet-and HFD-fed mice. During the clamp test, the BNP infusion into HFD-fed mice led to lower blood glucose levels and increased glucose infusion rates versus that into saline-treated HFD-fed mice. The BNP infusion also inhibited hepatic glucose production and decreased hepatic triglyceride levels concomitant with decreased expression of gluconeogenesis and lipogenesis-related genes, resulting in reduced levels of alanine aminotransferase and aspartate aminotransferase. BNP increased the phosphorylation of Akt and AMP-acti- vated protein kinase (AMPK) in the livers of HFD-fed mice compared to saline-fed HFD mice. The incubation of AML12 murine hepatocytes with BNP increased the basal levels of phosphorylated Akt and AMPK and recovered the phosphorylated Akt and phosphorylated AMPK levels reduced by palmitate treatment. Furthermore, BNP incubation prevented palmitate-induced increases in lipo- genesis gene expressions. Taken together, the current study's findings indicated that BNP ameliorates hepatic IR, resulting in reduced hepatic glucose production and hepatic steatosis.

• Journal of Physiology & Pathology in Korean Medicine
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• v.22 no.3
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• pp.642-648
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• 2008

The aim of this study is to investigate Chegameuiin-tang water extracts (CETE) have potent anti-obesity activities in a high fat diet-induced obesity mouse model. In this study, we designed three group (normal diet group, high fat diet group, high fat diet plus CETE group for 13-week oral administration). Increases in body weight and fat storage were inhibited by 13-week oral administration of CETE at a 500 mg/kg concentration in this animal model, while the amount of food intake was not affected. Results from blood lipid analysis showed that the levels of triglyceride, total cholesterol and LDL-cholesterol were significantly lowered by CETE administration, also HDL-cholesterol was increased more than high fat diet-induced obese mouse. To understand the underlying mechanism at the molecular level, the effects of CETE were examined on the expression of the genes involved in lipogenesis and lipolysis by real-time PCR. In epididymal fat of CETE-treated mice, the mRNA level of lipogenic genes such as sterol regulatory element binding protein 1 and fatty acid synthase were decreased, which was well correlated with the reduction of the epididymal fat weight. Also, CETE administration inhibited decreases of the hormone-sensitve lipase and lipoprotein lipase mRNA expressions, which are genes related with lipolysis. These results suggest that Chegameuiin-tang may have great potential as a novel anti-obesity agent.

• Microbiology and Biotechnology Letters
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• v.50 no.1
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• pp.135-146
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• 2022

Obesity is closely associated with profound dyslipidemia, insulin resistance, and fatty liver disease. Recent reports have suggested that alterations in gut microbiota can be linked to diet-induced obesity. In this study, the anti-obesity effects of Weissella confusa WIKIM51 isolated from kimchi were investigated, as evidenced by: i) reduced lipid accumulation and downregulated adipogenesis-related genes in 3T3-L1 adipocytes; ii) suppressed gains in body weight and epididymal fat mass; iii) reduced serum lipid levels, for example, triglyceride and total cholesterol; iv) increased serum adiponectin levels and reduced serum leptin levels; v) downregulated lipogenesis and upregulated β-oxidation-related genes in the epididymal fat; and vi) altered microbial communities. The collective evidence indicate the potential value of W. confusa WIKIM51 as a functional food supplement for the prevention and amelioration of obesity.

• Journal of Applied Biological Chemistry
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• v.66
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• pp.369-378
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• 2023

Smilax sieboldii is one of the Smilax species. A number of Smilax plants have multiple physiologically-active components and anti-inflammatory/anti-oxidant effects. Antiobesity effects induced by Smilax sieboldii have not been reported. In this study, we investigated the effects and molecular mechanisms of anti-obesity activity of 70% ethanol Smilax sieboldii extract (SSE). The anti-obesity effect of SSE was determined using 3T3-L1 adipocytes. We confirmed that SSE was not cytotoxic to murine 3T3-L1 preadipocytes, we evaluated SSE dose-dependently decreased the accumulation of lipids via an Oil Red O assay and triglyceride assay. These anti-obesity activities of SSE were mediated by the inhibition of adipogenesis-related marker genes (peroxisome proliferator activated receptor-γ, CCAAT-enhancer-binding protein α, and SREBP1c) and lipogenesis-related marker genes (fatty acid synthase and aP2). These results suggest that SSE has the potential to exert anti-obesity and anti-hyperlipidemia effects by regulating adipogenic transcription factors and inhibiting the expression of adipogenic markers.

• Asian-Australasian Journal of Animal Sciences
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• v.22 no.10
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• pp.1420-1428
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• 2009

In this study we cloned and characterized a novel lipid-accumulating gene, the oxidized low-density lipoprotein receptor 1 (OLR1), which is associated with lipogenesis. We analyzed the gene structure and detected the mRNA transcriptional expression levels in pig adipose tissues at different months of age (MA) and in different economic types (lean type and obese type) using real-time fluorescence quantitative PCR. OLR1 expression profile in different tissues of pig was analyzed. Finally, we studied the correlation between OLR1 and lipid metabolism related genes including peroxisome proliferator-activated $receptor{\gamma}2$ ($PPAR{\gamma}2$), fatty acid synthetase (FAS), triacylglycerol hydrolase (TGH), CAAT/enhancer binding protein $\alpha$ ($C/EBP{\alpha}$) and sterol regulatory element binding protein-1c (SREBP-1c). Results indicated that the OLR1 gene of the pig exhibited the highest homology with the cattle (84%), and the lowest with the mouse (27%). The signal peptide located from amino acid 38 to 60 and the domain from amino acid 144 to 256 were shared by the C-type lectin family. The expression level of OLR1 in pig lung was exceedingly higher than other tested tissues (p<0.01). In pig adipose tissue, the expression level of OLR1 mRNA increased significantly with growth (p<0.01). The expression level of OLR1 mRNA in obese-type pigs was significantly higher than that of lean-type pigs of the same monthly age (p<0.05). In adipose tissue, the expression of OLR1 correlated with $PPAR{\gamma}2$, FAS and SREBP-1c, but not TGH or C/EBP${\alpha}$. In conclusion, OLR1 was highly associated with fat deposition and its transcription, as suggested by high correlations, was possibly regulated by $PPAR{\gamma}2$ and SREBP-1c.