• Biomedical Science Letters
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• v.15 no.1
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• pp.101-103
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• 2009

The hepatocyte nuclear factor-$4{\alpha}$ (HNF-$4{\alpha}$), transcription factor involved in the regulation of serum lipid and glucose levels, has recently been reported to be associated with type 2 diabetes. Therefore, we investigated the genotype for the rs1884614 of HNF-$4{\alpha}$ gene in Korean population and compared genotype of patients with control group. 100 patients (Male 63, Female 37), who previously underwent type 2 diabetes (T2DM) and 100 controls (Male 36, Female 64) participated in this study. According to our present study there was no association between rs1884614 polymorphism in HNF-$4{\alpha}$ gene and T2DM in Koreans although other reports showed that HNF-$4{\alpha}$ polymorphisms might be associated with the pathogenesis of T2DM in Pima Indians et al. We assume that this finding should contribute to understanding of type 2 diabetes in Korean population in detail at genetic level.

• Journal of Life Science
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• v.19 no.3
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• pp.362-365
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• 2009

Type 2 diabetes is a typical polygenic disease complex, for which several common risk alleles have been identified. The hepatocyte nuclear factor-$4{\alpha}$ (HNF-$4{\alpha}$), a transcription factor involved in the regulation of serum lipid and glucose levels, has recently been associated with type 2 diabetes. Therefore, we investigated the genotype for the C>T polymorphism at position 12352 of the HNF-$4{\alpha}$ gene in Koreans and compared patient genotypes with those of the control group. 100 patients (63 males, 37 females) with a history of type 2 diabetes (T2DM) and 100 controls (36 males, 64 females) participated in this study. There was no association between 12352 C>T polymorphism in the HNF-$4{\alpha}$ gene and T2DM. The present study shows that HNF-$4{\alpha}$ 12352 C>T polymorphism may not be associated with the pathogenesis of T2DM. Further studies with larger populations may be needed for the development of diagnostic methods at a genetic level such as DNA chip.

• Korean Journal of Poultry Science
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• v.45 no.4
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• pp.253-260
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• 2018

The hepatocyte nuclear factor 4 alpha ($HNF4{\alpha}$) gene is related to lipid transport, including abdominal fat and growth, in chickens. Interestingly, the A543G SNP within the $HNF4{\alpha}$ gene has previously been reported to be associated with body weight in both broilers and Korean native chickens (KNCs). However, its exact position within the HNF4 is not yet reported. This study aimed to identify the position of the A543G SNP and to identify additional SNPs that can be used as genetic markers in KNCs. A total of 128 KNCs were used for the sequencing and analysis of these genetic associations. As a result, A543G SNP was located in intron 4 of the $HNF4{\alpha}$ gene; it is reported as rs731246957 in the NCBI database. Fourteen SNPs were detected in the sequenced portion of the $HNF4{\alpha}$ gene; three of these, rs731246957, rs736159604 and new SNP, intron 6 (249), were significantly related with growth in the chickens. In this study, the TT genotype of rs731246957, previously reported as A543G SNP, the GG genotype of rs736159604 and GT of new SNP have are highly associated with body weight from birth to 40 weeks of age in KNCs (P<0.01). These results suggest that rs736159604, rs731246957 and intron 6 (249) SNPs within the $HNF4{\alpha}$ gene could function as growth-related markers in the selective breeding of KNCs.

• Food Science of Animal Resources
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• v.37 no.4
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• pp.529-534
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• 2017

Probiotics have been known to reduce high-fat diet (HFD)-induced metabolic diseases, such as obesity, insulin resistance, and type 2 diabetes. We recently observed that Lactobacillus acidophilus NS1 (LNS1), distinctly suppresses increase of blood glucose levels and insulin resistance in HFD-fed mice. In the present study, we demonstrated that oral administration of LNS1 with HFD feeding to mice significantly reduces hepatic expression of phosphoenolpyruvate carboxykinase (PEPCK), a key enzyme in gluconeogenesis which is highly increased by HFD feeding. This suppressive effect of LNS1 on hepatic expression of PEPCK was further confirmed in HepG2 cells by treatment of LNS1 conditioned media (LNS1-CM). LNS1-CM strongly and specifically inhibited $HNF4{\alpha}-induced$ PEPCK promoter activity in HepG2 cells without change of $HNF4{\alpha}$ mRNA levels. Together, these data demonstrate that LNS1 suppresses PEPCK expression in the liver by regulating $HNF4{\alpha}$ transcriptional activity, implicating its role as a preventive or therapeutic approach for metabolic diseases.

• Parasites, Hosts and Diseases
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• v.49 no.4
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• pp.431-436
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• 2011

The onset, severity, and ultimate outcome of malaria infection are influenced by parasite-expressed virulence factors as well as by individual host responses to these determinants. In both humans and mice, liver injury follows parasite entry, persisting to the erythrocytic stage in the case of infection with the fatal strain of Plasmodium falciparum. Hepatic nuclear factor (HNF)-$1{\alpha}$ is a master regulator of not only the liver damage and adaptive responses but also diverse metabolic functions. In this study, we analyzed the expression of host HNF-$1{\alpha}$ in relation to malaria infection and evaluated its interaction with the 5'-untranslated region of subtilisin-like protease 2 (subtilase, Sub2). Recombinant human HNF-$1{\alpha}$ expressed by a lentiviral vector (LV HNF-$1{\alpha}$) was introduced into mice. Interestingly, differences in the activity of the 5'-untranslated region of the Pf-Sub2 promoter were detected in 293T cells, and LV HNF-$1{\alpha}$ was observed to influence promoter activity, suggesting that host HNF-$1{\alpha}$ interacts with the Sub2 gene.

• Journal of Nutrition and Health
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• v.47 no.3
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• pp.167-175
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• 2014

Purpose: Previous studies have shown that treatment with Smilax china L. leaf extract (SCLE) produces antidiabetic effects due to ${\alpha}$-glucosidase inhibition. In this study, we examined the mechanism underlying these antidiabetic effects by examining glucose uptake in HepG2 cells cultured with SCLE. Methods: Glucose uptake and glucokinase activity were examined using an assay kit. Expression of glucose transporter (GLUT)-2, GLUT-4, and HNF-$1{\alpha}$ was measured by RT-PCR or western blot. Results: Treatment with SCLE resulted in enhanced glucose uptake in HepG2 cells, and this effect was especially pronounced when cells were cultured in an insulin-free medium. SCLE induced an increase in expression of GLUT-2 but not GLUT-4. The increase in the levels of HNF-$1{\alpha}$, a GLUT-2 transcription factor, in total protein extract and nuclear fraction suggest that the effects of SCLE may occur at the level of GLUT-2 transcription. In addition, by measuring the change in glucokinase activity following SCLE treatment, we confirmed that SCLE stimulates glucose utilization by direct activation of this enzyme. Conclusion: These results demonstrate that the potential antidiabetic activity of SCLE is due at least in part to stimulation of glucose uptake and an increase in glucokinase activity, and that SCLE-stimulated glucose uptake is mediated through enhancement of GLUT-2 expression by inducing expression of its transcription factor, HNF-$1{\alpha}$.

• Korean Journal of Ecology and Environment
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• v.43 no.1
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• pp.55-68
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• 2010

The seasonal variation of microbial community, based on the bacteria, heterotrophic nanoflagellates (HNF), phytoplankton and ciliates, was investigated at three sites in the eutrophic brackish water of Lake Shihwa and its adjacent areas from May 2007 through May 2008. At the upstream-region site St. 1, compared to the other two sites, significantly lower salinities and higher concentrations of nutrients and chlorophyll $\alpha$ (Chl. $\alpha$) were recorded. The annual average abundances of bacteria at St. 1, St. 2 and St. 3 were $6.8{\times}10^6$, $7.4{\times}10^6$ and $4.6{\times}10^6\;cells\;mL^{-1}$, respectively. As for the annual average concentrations of HNF, $19{\times}10^2$, $6.7{\times}10^2$ and $5.9{\times}10^2\;cells\;mL^{-1}$, were recorded in St. 1, St. 2 and St. 3 respectively. The highest ciliate abundance appeared at St. 1 on 29 April, 2008 and in which, 99% were autotrophic ciliate Mesodinium rubrum (Myrionecta rubra). Significant linear correlations between the biomass of bacteria and Chl. $\alpha$ were found, however, no significant relationships between ciliates abudance/biomass and their prey organisms were detected in all three sites, implying relatively low energy transfer efficiencies between them. These results indicated that the trophic relationship between ciliates and their prey organisms in the microbial community might be influenced by indirect route since higher trophic level organisms did not directly correlate to those of lower trophic level, although high primary productions were detected in the eutrophic brackish water of Lake Shihwa and its adjacent areas.

• Journal of Physiology & Pathology in Korean Medicine
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• v.28 no.5
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• pp.499-505
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• 2014

Immunosuppressors cyclosporine A(CsA) and tacrolimus(FK506), the primary cellular target of which is calcineurin/nuclear factor of activated T cells(NFAT) signalling pathways, decrease beta-cell insulin content and mRNA expression. The posttransplantation diabetes mellitus(PTDM) is a frequent complication in immunosuppressive therapy. The present study was to examine the effect of a crude water extracts of medicinal herbs such as Sanguisorba officinalis(SOE) on the immunosuppressive activity with lymphocyte and insulin secretion in insulinoma cell lines with RIN-5mF. It was found that SOE treatment had effect of immunosuppressor on lymphocytes and also significantly increased insulin secretion in RIN-5mF compared to other agents. we might suggest a mechanism on insulin secretion by HNF4a. Taken together, the present study suggested that SOE might serve as immunosuppressive drug in PTDM.

• BMB Reports
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• v.46 no.6
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• pp.322-327
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• 2013

The ATP-binding cassette transporters ABCG5 and ABCG8 form heterodimers that limit absorption of dietary sterols in the intestine and promote cholesterol elimination from the body through hepatobiliary secretion. To identify cis-regulatory elements of the two genes, we have cloned and analyzed twenty-three evolutionary conserved region (ECR) fragments using the CMV-luciferase reporter system in HepG2 cells. Two ECRs were found to be responsive to the Liver-X-Receptor (LXR). Through elaborate deletion studies, regions containing putative LXREs were identified and the binding of $LXR{\alpha}$ was demonstrated by EMSA and ChIP assay. When the LXREs were inserted upstream of the intergenic promoter, synergistic activation by $LXR{\alpha}/RXR{\alpha}$ in combination with GATA4, $HNF4{\alpha}$, and LRH-1, which had been shown to bind to the intergenic region, was observed. In conclusion, we have identified two LXREs in ABCG5/ABCG8 genes for the first time and propose that these LXREs, especially in the ECR20, play major roles in regulating these genes.

• Korean Journal of Ecology and Environment
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• v.41 no.2
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• pp.174-187
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• 2008

In an effort to identify structure and function of microbial loop in Paldang reservoir, we monitored environmental and biological factors at Kyungan stream (station K), Paldang dam (station P) and the confluence of North and South Han River (station M) from March to December, 2005. DOC concentration was higher in March to May and November than the others. Nutrient concentration in station K detected relatively higher than that of two stations. Both of phosphate and silicate gradually increased at all stations until September, after then decreased. The highest Chl-$\alpha$ concentration was observed at all stations in April, and November. The carbon biomass of bacteria and HNF were relatively higher in March, May and August than the others, whereas that of the ciliate showed no significant difference in monthly fluctuation. Nevertheless, the significant relationships revealed between ciliate (P<0.001) and HNF (P<0.05) and bacterial density. Tintinnopsis cratera, Didinium sp., Vorticella sp., Paramecium sp. and Strombidium sp. were dominant species in ciliate community. The dominant species of phytoplankton were Stephanodiscus hantzschii and Cyclotella meneghiniana at almost stations in Spring, Summer and Autumn. However, Aulacoseira granulata accounted for >95% of phytoplankton biomass at station P and M in Autumn. The carbon biomass of zooplankton was highest at station P and M in June, and relatively higher biomass observed at all stations in August, October and November. Diaphanosoma brachyurum and Bosmina longirostris were dominant in stations P and M of June and in all stations of October and November, respectively. The maximum growth (A. granulata: $0.17\;d^{-1}$, S. hantzschii: $0.14\;d^{-1}$) and grazing rate (A. granulata: 1.93 preys $d^{-1}$, S. hantzschii: 1.63 preys $d^{-1}$) of Bosmina longirostris revealed in algal preys as Aulacoseira granulata and Stephanodiscus hantzschii. In conclusion, these results suggest that bacteria and phytoplankton can play the most crucial source as prey within microbial food chain in Spring and Summer and grazing food chain in Autumn, respectively.