• The Korean Journal of Physiology and Pharmacology
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• v.19 no.5
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• pp.451-460
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• 2015

Sirtuin 1 (SIRT1) is a mammalian $NAD^+$-dependent protein deacetylase that regulates cellular metabolism and inflammatory response. The organ-specific deletion of SIRT1 induces local inflammation and insulin resistance in dietary and genetic obesity. Macrophage-mediated inflammation contributes to insulin resistance and metabolic syndrome, however, the macrophage-specific SIRT1 function in the context of obesity is largely unknown. C57/BL6 wild type (WT) or myeloid-specific SIRT1 knockout (KO) mice were fed a high-fat diet (HFD) or normal diet (ND) for 12 weeks. Metabolic parameters and markers of hepatic steatosis and inflammation in liver were compared in WT and KO mice. SIRT1 deletion enhanced HFD-induced changes on body and liver weight gain, and increased glucose and insulin resistance. In liver, SIRT1 deletion increased the acetylation, and enhanced HFD-induced nuclear translocation of nuclear factor kappa B (NF-${\kappa}B$), hepatic inflammation and macrophage infiltration. HFD-fed KO mice showed severe hepatic steatosis by activating lipogenic pathway through sterol regulatory element-binding protein 1 (SREBP-1), and hepatic fibrogenesis, as indicated by induction of connective tissue growth factor (CTGF), alpha-smooth muscle actin (${\alpha}$-SMA), and collagen secretion. Myeloid-specific deletion of SIRT1 stimulates obesity-induced inflammation and increases the risk of hepatic fibrosis. Targeted induction of macrophage SIRT1 may be a good therapy for alleviating inflammation-associated metabolic syndrome.

• The Journal of Korean Obstetrics and Gynecology
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• v.31 no.1
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• pp.20-42
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• 2018

Objectives: This study was designed to investigate anti-obesity effects the improvement effects of Gyejibongnyeong-hwan and Gyejibongnyeong-hwan-Gangji-hwan (CIPPDF) in a ob/ob mouse model. Methods: Seven-week old mice (wild-type C57BL/6J and ob/ob) were used for all experiments. Wild-type C57BL/6J mice were used as normal group and obese ob/ob mice were randomly divided into 4 groups. a normal group given a standard diet, an obese control group given a standard diet with CIPP (300 mg/kg), CIPPDF (1) (300+300 mg/kg), CIPPDF (2) (300+600 mg/kg) respectively. After 10 weeks of treatment, body weight gain, feeding efficiency ratio, blood lipid markers, mRNA levels of genes involved in fatty acid ${\beta}-oxidation$ and lipogenesis in in-vivo, were examined. Results: 1. Body weight gain and Feeding efficiency ratio were significantly decreased in CIPPDF (1) compared with control. Fat mass was significantly decreased in CIPPDF (2) in EAT compared with control. 2. Consistent their effects on body weight gain and fat mass, circulating concentrations of LDL-cholesterol were decreased in CIPPDF (1), CIPPDF (2) groups compared with control. 3. MCAD mRNA levels of genes was increased in CIPPDF (1), CIPPDF (2) groups in the liver, epididymal adipose tissue compared with control. VLCAD mRNA levels of genes was increased in CIPPDF (1), CIPPDF (2) groups in the skeletal muscle compared with control. 4. $PPAR{\gamma}$ mRNA was decreased in CIPPDF (1) in the liver compared with control. SCD1 mRNA was decreased in CIPPDF (1), CIPPDF (2) groups in the epididymal adipose tissue compared with control. Conclusions: In conclusion, These results suggest that CIPPDF not only decrease feeding efficiency ratio, and LDL-cholesterol, but also reduce EAT fat mass contributing to the improvement of ovesity. CIPPDF also were increased in mRNA levels of genes involved in fatty acid ${\beta}-oxidation$ and decreased in mRNA levels of genes involved in lipogenesis.

• Journal of Life Science
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• v.21 no.1
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• pp.155-158
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• 2011

Uncoupling protein (UCP) 3 has a number of proposed roles in the regulation of fatty acid metabolism. A number of polymorphisms in the human UCP3 gene have been identified, and the correlation with obesity related phenotypes evaluated. The objective of this study was to identify SNP in porcine UCP3 gene and to investigate the effect of the SNP on economic traits. The sequencing analysis method was used to identify nucleotide polymorphisms at position 1405 bp (Genebank accession No : AY739704) in porcine UCP3 gene. The SNP (G150R), located in the exon 3, changed the amino acid to glycine (GGG) from arginine (AGG). This G150R showed three genotypes - GG, GR and RR - by digestion with the restriction enzyme Sma Ⅰ using the PCR-RFLP method. The G150R showed significant effects only on back fat (P<0.05). Animals with the genotype GG had significantly higher back fat thickness (1.358 cm) than animals with the genotype GR (1.288 cm, P<0.05) and RR (1.286 cm, P<0.05). However, the genotypes had no significant association with ADG and days to 90kg. According to results of this study, a G allele of the G150R was found to have a significant effect on back fat thickness. It will be possible to use SNP markers on selected pigs to improve backfat thickness, an important economic trait.

• Journal of Biomedical and Translational Research
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• v.19 no.4
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• pp.116-124
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• 2018

Korean Native Pig (KNP) has a uniform black coat color, excellent meat quality, white colored fat, solid fat structure and good marbling. However, its growth performance is low, while the western origin Yorkshire pig has high growth performance. To take advantage of the unique performance of the two pig breeds, we raised crossbreeds (KNP ${\times}$ Yorkshire to make use of the heterotic effect. We then analyzed the liver transcriptome as it plays an important role in fat metabolism. We sampled at two stages: 10 weeks and at 26 weeks. The stages were chosen to correspond to the change in feeding system. A total of 16 pigs (8 from each stage) were sampled and RNA sequencing was performed. The reads were mapped to the reference genome and differential expression analysis was performed with edgeR package. A total of 324 genes were found to be significantly differentially expressed (${\left|log2FC\right|}$ > 1 & q < 0.01), out of which 180 genes were up-regulated and 144 genes were down-regulated. Principal Component Analysis (PCA) showed that the samples clustered according to stages. Functional annotation of significant DEGs (differentially expressed genes) showed that GO terms such as DNA replication, cell division, protein phosphorylation, regulation of signal transduction by p53 class mediator, ribosome, focal adhesion, DNA helicase activity, protein kinase activity etc. were enriched. KEGG pathway analysis showed that the DEGs functioned in cell cycle, Ras signaling pathway, p53 signaling pathway, MAPK signaling pathway etc. Twenty-nine transcripts were also part of the DEGs, these were predominantly Cys2His2-like fold group (C2H2) family of zinc fingers. A protein-protein interaction (PPI) network analysis showed that there were three highly interconnected clusters, suggesting an enrichment of genes with similar biological function. This study presents the first report of liver tissue specific gene regulation in a cross-bred Korean pig.

• Nutrition Research and Practice
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• v.15 no.6
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• pp.673-685
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• 2021

BACKGROUND/OBJECTIVES: Obesity is associated with the impaired regulation of T cells characterized by increased numbers of Th1 and Th17 cells and the dysregulation of vitamin D metabolism. Both obesity and vitamin D have been reported to affect autophagy; however, a limited number of studies have investigated the effects of vitamin D on T cell autophagy in obese mice. Therefore, we aimed to determine whether in vitro treatment with vitamin D affects the proliferation, function, and autophagy of T cells from obese and control mice. MATERIALS/METHODS: Five-week-old male C57BL/6 mice were fed control or high-fat diets (10% or 45% kcal fat: CON or HFDs, respectively) for 12 weeks. Purified T cells were stimulated with anti-CD3 and anti-CD28 monoclonal antibodies and cultured with either 10 nM 1,25(OH)₂D₃ or 0.1% ethanol (vehicle control). The proliferative response; expression of CD25, Foxp3, RORγt, and autophagy-related proteins (LC3A/B, SQSTM1/P62, BECLIN-1, ATG12); and the production of interferon (IFN)-γ, interleukin (IL)-4, IL-17A, and IL-10 by T cells were measured. RESULTS: Compared with the CON group, T cell proliferation tended to be lower, and the production of IFN-γ was higher in the HFD group. IL-17A production was reduced by 1,25(OH)2D₃ treatment in both groups. The LC3 II/I ratio was higher in the HFD group than the CON group, but P62 did not differ. We observed no effect of vitamin D treatment on T cell autophagy. CONCLUSIONS: Our findings suggest that diet-induced obesity may impair the function and inhibit autophagy of T cells, possibly leading to the dysregulation of T cell homeostasis, which may be behind the aggravation of inflammation commonly observed in obesity.

• Journal of Ginseng Research
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• v.46 no.4
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• pp.561-571
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• 2022

Background: Ginsenoside Rb1 (GRb1) is capable of regulating lipid and glucose metabolism through its action on adipocytes. However, the beneficial role of GRb1-induced up-regulation of adiponectin in liver steatosis remains unelucidated. Thus, we tested whether GRb1 ameliorates liver steatosis and insulin resistance by promoting the expression of adiponectin. Methods: 3T3-L1 adipocytes and hepatocytes were used to investigate GRb1's action on adiponectin expression and triglyceride (TG) accumulation. Wild type (WT) mice and adiponectin knockout (KO) mice fed high fat diet were treated with GRb1 for 2 weeks. Hepatic fat accumulation and function as well as insulin sensitivity was measured. The activation of AMPK was also detected in the liver and hepatocytes. Results: GRb1 reversed the reduction of adiponectin secretion in adipocytes. The conditioned medium (CM) from adipocytes treated with GRb1 reduced TG accumulation in hepatocytes, which was partly attenuated by the adiponectin antibody. In the KO mice, the GRb1-induced significant decrease of TG content, ALT and AST was blocked by the deletion of adiponectin. The elevations of GRb1-induced insulin sensitivity indicated by OGTT, ITT and HOMA-IR were also weakened in the KO mice. The CM treatment significantly enhanced the phosphorylation of AMPK in hepatocytes, but not GRb1 treatment. Likewise, the phosphorylation of AMPK in liver of the WT mice was increased by GRb1, but not in the KO mice. Conclusions: The up-regulation of adiponectin by GRb1 contributes to the amelioration of liver steatosis and insulin resistance, which further elucidates a new mechanism underlying the beneficial effects of GRb1 on obesity.

• The Korea Journal of Herbology
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• v.29 no.2
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• pp.23-31
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• 2014

Objectives : This study was undertaken to verify the effects of Massa Medicata Fermentata (MMF) on nonalcoholic fatty liver disease (NAFLD) using high fat diet-fed male mice. Methods : Fifty four male C57BL/6N mice (age matched) were used for all experiments. Nine standard chow diet-fed mice were used as normal group and forty five high fat diet-fed obese mice were randomly divided into 5 groups: control, atorvastatin-10mg/kg, MMF(1)-62.5mg/kg, MMF(2)-125mg/kg and MMF(3)-250mg/kg. After all groups were treated with several kinds of diets for 8 weeks, we measured body weight gain, adipose tissue weights, plasma lipid and glucose metabolism, visceral organ weights, histological analysis for liver on the mice. Results : MMF-treated mice had lower body weight gain compared with controls. Among MMF-treated mice, the effect was magnified in MMF(2). MMF(3)-treated mice had lower blood plasma total cholesterol (TC) and glucose level compared with controls. MMF decreased hepatic lipid accumulation, liver fibrosis and liver inflammation of mice compared with controls. The effects was maximized in MMF(2) and atorvastatin. Blood plasma aspartate aminotransferase (AST), alanine aminotransferase (ALT), ${\gamma}$-glutamyltransferase (${\gamma}$-GT) concentrations tends to be decreased by MMF compared with controls. Blood plasma AST, ALT, ${\gamma}$-GT concentrations and organ weights were not changed by MMF, indicating that all three kinds of MMF do not show any hepatotoxicity. Conclusions : These results suggest that MMF improves NAFLD by reducing body weight gain, hepatic lipid accumulation, liver fibrosis, liver inflammation.

• Animal Bioscience
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• v.35 no.9
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• pp.1327-1339
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• 2022

Objective: Fat deposition in poultry is an important factor in production performance and meat quality research. miRNAs also play important roles in regulating adipocyte differentiation process. This study was to investigate the expression patterns of miRNAs in duck adipocytes after differentiation and explore the role of miR-214 in regulating carnitine palmitoyltransferases 2 (CPT2) gene expression during duck adipocyte differentiation. Methods: Successful systems for the isolation, culture, and induction of duck primary fat cells was developed in the experiment. Using Illumina next-generation sequencing, the miRNAs libraries of duck adipocytes were established. miRanda was used to predict differentially expressed (DE) miRNAs and their target genes. The expression patterns of miR-214 and CPT2 during the differentiation were verified by quantitative real-time polymerase chain reaction and western blot. Luciferase reporter assays were used to explore the specific regions of CPT2 targeted by miR-214. We used a miR-214 over-expression strategy in vitro to further investigate its effect on differentiation process and CPT2 gene transcription. Results: There were 481 miRNAs identified in duck adipocytes, included 57 DE miRNA candidates. And the 1,046 targets genes of DE miRNAs were mainly involved in p53 signaling, FoxO signaling, and fatty acid metabolism pathways. miR-214 and CPT2 showed contrasting expression patterns before and after differentiation, and they were selected for further research. The expression of miR-214 was decreased during the first 3 days of duck adipocytes differentiation, and then increased, while the expression of CPT2 increased both in the transcriptional and protein level. The luciferase assay suggested that miR-214 targets the 3'untranslated region of CPT2. Overexpression of miR-214 not only promoted the formation of lipid droplets but also decreased the protein abundance of CPT2. Conclusion: Current study reports the expression profile of miRNAs in duck adipocytes differentiated for 4 days. And miR-214 has been proved to have the regulator potential for fat deposition in duck.

• Journal of Animal Science and Technology
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• v.46 no.3
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• pp.347-354
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• 2004

Four Holstein cows were used in a 4 ${\times}$ 4 Latin square experiment to study effects of fat sources on rumen metabolism and digestibility of nutrients. All cows were fed a total mixed diets containing 60% silage and 40% concentrate. The four concentrates were formulated to contain either Megalac(MEG), formaldehyde-treated whole linseed(LIN), a mixture (50 : 50, oil basis) of fish oil and formaldehyde-treated whole linseed(MIX), or no fat source in the concentrate but 500g per day of linseed oil being infused into the duodemm (OIL). The rumen pH was lowest in OIL among the treatments(P < 0.05), but ammonia N concentration in the rumen was not significantly different among the treatments. The differences of total VFA, acetate, propionate, iso-butyrate and iso-valerate concentrations were not significant among the treatments. While, butyrate and valerate were highest in OIL and lowest in MEG(P < 0.05 and P <0.01, respectively). In addition, A:P ratio was also highest in OIL and lowest in MEG(P < 0.05). As expected, intake of nutrients(DM, OM, NDF and ADF) was lowest in OIL among the treatments(P < 0.01). However, all nutrients flow to the duodenum, and digestion in the rumen and total tract were not significantly different among the treatments. Intake of N was highest in MEG, but lowest in OIL treatment(P < 0.01). Duodenal flow of total N, nonammonia N and microbial N was not significantly different across the treatments. In addition, microbial synthesis and ammonia N and total N digestibility were not affected by different dietary fat sources. The present results show that fermentative characteristic and microbial efficiency in the rumen, and nutrients digestibility in the rumen and total tract were not depressed by supplementation of as much as 6% dietary fat sources.

• Journal of the Korean Society of Food Science and Nutrition
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• v.40 no.10
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• pp.1411-1416
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• 2011

In this study, we investigated the anti-obesity activity of Aceriphyllum rossii ethanol extract on rat fed a high fat diet. Male SD rats were divided into four groups. Group 1 was the control. Group 2 was fed a high-fat diet. Group 3 was the positive control, fed a high-fat diet supplemented with Garcinia Cambogia extracts. Group 4 was fed a high fat diet supplemented with ethanol extracts of Aceriphyllum rossii (EEAR). Precisely 166 mg/kg of powdered Garcinia Cambogia extracts was used for Group 3. Also, 250 mg/kg of EEAR was used for Group 4. The Body weight increased Group 2, but decreased Group 4. The serum total cholesterol in Group 2 increased by 15.26% when compared to Group 1, but only increased 5.29% in Group 3 and 4.29% in Group 4. The liver and mesenteric adipose tissue weights of Group 2 increased compared to Group 1, whereas they decreased in Group 3 and Group 4. As a result of measuring the concentration of triglycerides in extracted livers, Group 2 showed a significant increase compared to the Group 1, and Groups 3 and 4 showed significant decrease compared Group 2. These results suggest that Aceriphyllum rossii ethanol extracts may be useful as an anti-obesity agent.