• Korean Journal of Veterinary Service
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• v.44 no.4
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• pp.195-207
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• 2021

Species A rotaviruses (RVAs) replicate and assemble their immature particles within electron dense compartments known as viroplasms, where lipid droplets (LDs) interact with the viroplasm and facilitate viral replication. Despite the importance of LD formation in the life cycle of RVAs, the upstream molecules modulating LD formation remain unclear. This study aimed to find out the role of sterol regulatory element-binding proteins (SREBPs) in reprogramming of LD formation after RVA infection. Here, we demonstrate that RVA infection reprograms the sterol regulatory element-binding proteins (SREBPs)-dependent lipogenic pathways in virus-infected cells, and that both SREBP-1 and -2 transactivated genes, which are involved in fatty acid and cholesterol biosynthesis, are essential for LD formation. Our results showed that pharmacological inhibition of SREBPs using AM580 and betulin and inhibition of their downstream cholesterol biosynthesis (simvastatin for HMG-CoA reductase) and fatty acid enzymes (TOFA) negatively modulated the intracellular triacylglycerides and cholesterol levels and their resulting LD and viroplasm formations. Interestingly, pharmacological inhibition of SREBPs significantly reduced RVA protein synthesis, genome replication and progeny production. This study identified SREBPs-mediated lipogenic reprogramming in RVA-infected host cells, which facilitates virus replication through LD formation and its interaction with viroplasms, suggesting that SREBPs can be a potential target for the development of efficient and affordable therapeutics against RVA infection.

• Asian-Australasian Journal of Animal Sciences
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• v.30 no.2
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• pp.160-166
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• 2017

Objective: This study identifies single-nucleotide polymorphisms (SNP) or gene combinations that affect the flavor and quality of Korean cattle (Hanwoo) by using the SNP Harvester method. Methods: Four economic traits (oleic acid [C18:1], saturated fatty acids), monounsaturated fatty acids, and marbling score) were adjusted for environmental factors in order to focus solely on genetic effects. The SNP Harvester method was used to investigate gene combinations (two-way gene interactions) associated with these economic traits. Further, a multifactor dimensionality reduction method was used to identify superior genotypes in gene combinations. Results: Table 3 to 4 show the analysis results for differences between superior genotypes and others for selected major gene combinations using the multifactor dimensionality reduction method. Environmental factors were adjusted for in order to evaluate only the genetic effect. Table 5 shows the adjustment effect by comparing the accuracy before and after correction in two-way gene interactions. Conclusion: The g.3977-325 T>C and (g.2988 A>G, g.3977-325 T>C) combinations of fatty acid-binding protein4 were the superior gene, and the superior genotype combinations across all economic traits were the CC genotype at g.3977-325 T>C and the AACC, GACC, GGCC genotypes of (g.2988 A>G, g.3977-325 T>C).

• Asian-Australasian Journal of Animal Sciences
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• v.25 no.8
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• pp.1055-1062
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• 2012

Two SNPs, i.e. L127V and T172M, of bovine growth hormone (GH) causing the presence of GH gene haplotypes A, B, and C was previously shown to alter intramuscular fatty acid (FA) composition in Japanese Black (JB) heifers. To determine the SNP effect on somatotropic hormone concentration and lipogenesis, we measured plasma GH, insulin, and insulin-like growth factor-1 (IGF-1) concentrations. We also measured mRNA levels of fatty acid synthase (FASN), stearoyl-coA desaturase (SCD), and sterol regulatory element binding proteins-1 (SREBP-1) and FA composition in diaphragm tissues. Heifers with genotype CC had the lowest plasma insulin concentration and FASN and SCD mRNA levels among genotypes. FASN mRNA levels in haplotype A tended to positively correlate with saturated FA (SFA) content and negatively correlated with C18:2 and unsaturated FA (USFA) contents. SCD mRNA levels in haplotype A positively correlated with monounsaturated FA (MUFA) contents and negatively correlated with C18:0 content. They also tended to positively correlate with C16:1, C18:1, and USFA contents and USFA/SFA ratio and negatively correlate with SFA content. Taken together, GH gene polymorphism affects the lipogenic genes expression levels and their relationships with fatty acid compositions in diaphragm tissues of JB heifers at 31 months of age.

• Journal of Life Science
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• v.33 no.4
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• pp.315-324
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• 2023

The underlying action of policosanol in lowering cholesterol level has not yet been clearly elucidated. Several recent studies have suggested that sterol regulatory element-binding proteins (SREBP)-1c play a role in the regulation of cholesterol synthesis via the fatty acid synthesis pathway. To date, no study has evaluated the effects of policosanol on SREBP-1c-mediated fatty acid synthesis. Therefore, this study aimed to investigate whether the SREBP-1c-mediated fatty acid biosynthetic pathway is associated with the cholesterol-lowering effects of policosanol. Seven-week-old C57BL/6 male mice were randomly divided into 7 groups (n=7 per group) and treated for 8 weeks as follows: 1) normal diet (normal control), 2) high-fat diet (HFD), 3) HFD+ethanol (Pol-0), 4) HFD+policosanol 1 mg/kg (Pol-1), 5) HFD+policosanol 2 mg/kg (Pol-2), 6) HFD+policosanol 4 mg/kg (Pol-4), and 7) HFD+simvastatin 50 ㎍/kg (positive control). Policosanol and simvastatin were administered at the same time every day while maintaining the HFD. Body weight and food intake were measured weekly for 8 weeks. After 8 weeks, serum cholesterol levels were measured, histological analysis was carried out, and the expressions of SREBP-1c and fatty acid synthase (FAS) in the liver tissues were examined. Policosanol reduced body weight and the amount of food intake in a dose-dependent manner. Serum cholesterol levels were significantly lowered in the Pol-1 and Pol-4 groups. The expression of SREBP-1c and FAS was also significantly decreased in the Pol-4 group. These results suggest that the cholesterol-lowering effects of policosanol can occur due to the inhibition of the expression of SREBP-1c and FAS.

• Journal of Life Science
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• v.24 no.11
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• pp.1224-1230
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• 2014

The red radish (Raphanus sativus L.; RR) sprout is a plant of the cruciferous family. In this study, we elucidated the effect of the water extract of RR sprout (RRSE) against ${\alpha}$-amylase, ${\alpha}$-glucosidase, and pancreatic lipase enzyme activity and adipogenesis in 3T3-L1 preadipocytes. ${\alpha}$-amylase, ${\alpha}$-glucosidase, and pancreatic lipase enzyme activity was inhibited in a concentration-dependent manner by RRSE treatment. RSSE also abolished adipocyte differentiation and lipid and triglyceride accumulation without cytotoxicity in 3T3-L1 adipocytes. In addition, RRSE modulated the expression of the proteins related to adipogenic transcription factors: peroxisome proliferator-activated receptor (PPAR)${\gamma}$, sterol regulatory element-binding protein 1 (SREBP-1), and CCAT/enhancer binding protein (C/EBP)${\alpha}$. RRSE also suppressed expression of the proteins responsible for lipid synthesis, transport, and storage: adiponectin, fatty acid synthesis (FAS), perilipin, and fatty acid bind protein-4 (FABP4). This study showed that RRS treatment has the potential to inhibit obesity by controlling the expression of adipogenic transcription factors and adipogenic proteins.

• Korean Journal of Food Science and Technology
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• v.51 no.6
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• pp.558-564
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• 2019

Hypertriglyceridemia is one of the metabolic syndrome that is often observed as a result of lipid abnormalities. It is associated with other lipids, metabolic disorders, cardiovascular disease and liver disease. Korean red ginseng is known to affect obesity, dyslipidemia, liver disease and liver function, but the mechanism of its effect is not clear. This study examined the beneficial effects of hypertriglyceridemia and the mechanism of action of Jinan red ginseng extract (JRG) in hepatoma cells. To measure the levels of triglyceride accumulation, we studied the expression of proteins and mRNAs related to lipidogenesis in hepatoma cells (Huh7 and HepG2). JRG decreases the lipidogenic markers, peroxisome proliferator-activated receptor γ (PPARγ), CCAAT-enhancer-binding proteins α (C/EBPα) and C/EBPβ which are major regulators of triglyceride synthesis in hepatoma cells. We also found that JRG reduced sterol regulatory element binding proteins 1c (SREBP-1c), C/EBPα and C/EBPβ by regulating liver X receptor (LXR) and stearoyl CoA desaturase (SCD) expressions. In addition, the first-limited step of synthesis triglyceride (TG), glycerol-3-phosphate (G3P) is decreased by JRG. These results suggest that the anti-hypertriglyceride effect of JRG in hepatoma cells could be accompanied with the inhibition of lipidogenic transcription factors by regulating LXR and SCD expression.

• Journal of Life Science
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• v.31 no.9
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• pp.796-805
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• 2021

Hepatic endoplasmic reticulum (ER) stress contributes to the development of steatosis and insulin resistance. The components of unfolded protein response (UPR) regulate lipid metabolism. Recent studies have reported an association between ER stress and aberrant cellular lipid control; moreover, research has confirmed the involvement of sterol regulatory element-binding proteins (SREBPs)-the central regulators of lipid metabolism-in the process. However, the exact role of SREBPs in controlling lipid metabolism during ER stress and its contribution to fatty liver disease remain unknown. Here, we show that SREBP-1c deficiency protects against ER stress-induced hepatic steatosis in mice by regulating UPR, inflammation, and fatty acid oxidation. SREBP-1c directly regulated inositol-requiring kinase 1α (IRE1α) expression and mediated ER stress-induced tumor necrosis factor-α activation, leading to a reduction in expression of peroxisome proliferator-activated receptor γ coactivator 1-α and subsequent impairment of fatty acid oxidation. However, the genetic ablation of SREBP-1c prevented these events, alleviating hepatic inflammation and steatosis. Although the mechanism by which SREBP-1c deficiency prevents ER stress-induced inflammatory signaling remains to be elucidated, alteration of the IRE1α signal in SREBP-1c-depleted Kupffer cells might be involved in the signaling. Overall, the results suggest that SREBP-1c plays a crucial role in the regulation of UPR and inflammation in ER stress-induced hepatic steatosis.

• Nutrition Research and Practice
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• v.18 no.2
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• pp.180-193
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• 2024

BACKGROUND/OBJECTIVES: Obesity is a major cause of metabolic disorders; to prevent obesity, research is ongoing to develop natural and safe ingredients with few adverse effects. In this study, we determined the anti-obesity effects of Rosa multiflora root extract (KWFD-H01) in 3T3-L1 adipocytes and Sprague-Dawley (SD) rats. MATERIALS/METHODS: The anti-obesity effects of KWFD-H01in 3T3-L1 adipocytes and SD rats were examined using various assays, including Oil Red O staining, gene expression analyses, protein expression analyses, and blood biochemical analyses. RESULTS: KWFD-H01 reduced intracellular lipid accumulation and inhibited the mRNA expression of peroxisome proliferator-activated receptor γ (PPARγ), cytidine-cytidine-adenosine-adenosine-thymidine (CCAAT)/enhancer binding proteins (C/EBPα), sterol regulatory element-binding transcription factor 1 (SREBP-1c), acetyl-CoA carboxylase (ACC), and fatty acid synthase (FAS) in 3T3-L1 cells. KWFD-H01 also reduced body weight, weight gain, and the levels of triglycerides, total and LDL-cholesterol, glucose, and leptin, while increasing high-density lipoprotein-cholesterol and adiponectin in SD rats. PPARγ, C/EBPα, SREBP-1c, ACC, and FAS protein expression was inhibited in the epididymal fat of SD rats. CONCLUSION: Overall, these results confirm the anti-obesity effects of KWFD-H01 in 3T3-L1 adipocytes and SD rats, indicating their potential as baseline data for developing functional health foods or pharmaceuticals to control obesity.

• The Korean Journal of Physiology and Pharmacology
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• v.23 no.3
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• pp.161-169
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• 2019

Fumigaclavine C (FC), an active indole alkaloid, is obtained from endophytic Aspergillus terreus (strain No. FC118) by the root of Rhizophora stylosa (Rhizophoraceae). This study is designed to evaluate whether FC has anti-adipogenic effects in 3T3-L1 adipocytes and whether it ameliorates lipid accumulation in high-fat diet (HFD)-induced obese mice. FC notably increased the levels of glycerol in the culture supernatants and markedly reduced lipid accumulation in 3T3-L1 adipocytes. FC differentially inhibited the expressions of adipogenesis-related genes, including the peroxisome proliferator-activated receptor proteins, CCAAT/enhancer-binding proteins, and sterol regulatory element-binding proteins. FC markedly reduced the expressions of lipid synthesis-related genes, such as the fatty acid binding protein, lipoprotein lipase, and fatty acid synthase. Furthermore, FC significantly increased the expressions of lipolysis-related genes, such as the hormone-sensitive lipase, Aquaporin-7, and adipose triglyceride lipase. In HFD-induced obese mice, intraperitoneal injections of FC decreased both the body weight and visceral adipose tissue weight. FC administration significantly reduced lipid accumulation. Moreover, FC could dose-dependently and differentially regulate the expressions of lipid metabolism-related transcription factors. All these data indicated that FC exhibited anti-obesity effects through modulating adipogenesis and lipolysis.

• Korean Journal of Food Science and Technology
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• v.53 no.2
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• pp.149-153
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• 2021

Mandarin peel (MP) is a by-product of the processing of citrus juice or other products. This study aimed to investigate the potential anti-obesity effect of an enzymatic extract of MP on the inhibition of adipogenesis in 3T3-L1 adipocytes. The enzymatic extract (MPCE) was prepared using the commercial food-grade carbohydrase Celluclast. Lipid accumulation and triglyceride levels were significantly lower in MPCE-treated cells than in untreated cells. In addition, MPCE treatment reduced the protein expression levels of peroxisome proliferator-activated receptor-γ, CCAAT/enhancer-binding protein α, sterol regulatory element-binding protein 1, and fatty acid-binding protein 4. These results suggest that MPCE inhibits adipogenesis by downregulating the expression levels of adipogenesis-related proteins. Therefore, the current findings demonstrate that MPCE possesses potent anti-obesity properties and could be a potential ingredient in functional food industries.