• Journal of Korean Medicine for Obesity Research
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• v.14 no.2
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• pp.55-62
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• 2014

Objective: The prevalence of metabolic syndrome and type 2 diabetes is increasing worldwide. Mitochondrial dysfunction is known to be involved in insulin resistance and obesity, researches have been increasing highly. Astragali Radix extract (ARE) or its main components have been shown to perform comparably to insulin by significantly reducing blood glucose levels in animal models however, the influence on mitochondrial dysfunction are not well understood. Methods: ARE (0.2, 0.5 and 1.0 mg/ml) or metformin (2.5 mM) were treated in C2C12 after 6 day-differentiation. The expressions of adenosine monophosphate (AMP)-activated protein kinase (AMPK) and phosphorylation AMPK, peroxisome proliferators-activated receptror ${\gamma}$ coactivator $1{\alpha}$ ($PGC1{\alpha}$), nuclear respiratory factors 1 (NRF1), mitochondrial transcription factor (Tfam) and myosin heavy chain were detected with western blotting or polymerase chain reaction analysis. The morphological changes were also investigated. Results: ARE dose dependently increased phosphorylation of AMPK and respectively activated mRNA expressions of $PGC1{\alpha}$, NRF1 and Tfam which are mitochondrial biogenesis regulators. Furthermore, there were some morphologic differences of differentiated cells between ARE treatment and control. Conclusions: This study suggests that ARE has the potential to increase muscle mitochondrial function by activating AMPK and $PGC1{\alpha}$.

• The Korean Journal of Food & Health Convergence
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• v.4 no.4
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• pp.18-25
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• 2018

Proteins play a key role in many functions such as metabolic activity, differentiation, as cargos and cell fate regulators. It is necessary to know about the markers involved in male fertility in order to develop remedies for the treatment of male infertility. But, the role of the proteins is not limited to particular function in the biological systems. Some of the proteins act as ion channels such as catsper and proteins like Nanos acts as a translational repressor in germ cells and expressed in prenatal period whose role in male fertility is uncertain. Rbm5 is a pre mRNA splicing factor necessary for sperm differentiation whose loss of function results deficit in sperm production. DEFB114 is a beta defensin family protein necessary for sperm motility in LPS challenged mice where as TEX 101 is a plasma membrane specific germ cell protein whose function is not clearly known u to now. Gpr56 is another adhesion protein whose null mutation leads to arrest of production of pups in rats. Amyloid precursor protein role in Alzheimer's disease is already known but it plays an important role in male fertility also but its function is uncertain and has to be considered while targeting APP during the treatment of Alzheimer's disease. The study on amyloid precursor protein in male fertility is a novel thing but requires further study in correlation to alzheimer's disease.

• Genomics & Informatics
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• v.13 no.3
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• pp.76-80
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• 2015

Type 2 diabetes mellitus is a complex metabolic disorder associated with multiple genetic, developmental and environmental factors. The recent advances in gene expression microarray technologies as well as network-based analysis methodologies provide groundbreaking opportunities to study type 2 diabetes mellitus. In the present study, we used previously published gene expression microarray datasets of human skeletal muscle samples collected from 20 insulin sensitive individuals before and after insulin treatment in order to construct insulin-mediated regulatory network. Based on a motif discovery method implemented by iRegulon, a Cytoscape app, we identified 25 candidate regulons, motifs of which were enriched among the promoters of 478 up-regulated genes and 82 down-regulated genes. We then looked for a hierarchical network of the candidate regulators, in such a way that the conditional combination of their expression changes may explain those of their target genes. Using Genomica, a software tool for regulatory network construction, we obtained a hierarchical network of eight regulons that were used to map insulin downstream signaling network. Taken together, the results illustrate the benefits of combining completely different methods such as motif-based regulatory factor discovery and expression level-based construction of regulatory network of their target genes in understanding insulin induced biological processes and signaling pathways.

• Journal of agriculture & life science
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• v.43 no.4
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• pp.15-20
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• 2009

The transition from pregnancy to lactation, commonly referred to as the "transition period" is characterized by dramatic changes in metabolic processes and their regulation in order to prepare the dairy cow for parturition and lactogenesis. An important adaptation to lactation is the increase in gluconeogenesis by the liver to meet the tremendous increase in demand of glucose for lactose synthesis, and the accumulation of lipid in adipose tissue during pregnancy, its mobilization that begins prior to lactation and the dramatic increase in plasma NEFA concentration early lactation. Epinephrine and insulin, the homeostatic regulators of metabolism are responsible for the adaptations of lipid and carbohydrate metabolism in support of milk production along with mobilization of body fat to meet overall energy demands because dry matter intake is insufficient to meet these demands during early lactation.

• Asian-Australasian Journal of Animal Sciences
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• v.32 no.9
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• pp.1458-1468
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• 2019

Objective: As one of the most important metabolic organs, the liver plays vital roles in modulating the lipid metabolism. This study was to compare miRNA expression profiles of the Large White liver between two different developmental periods and to identify candidate miRNAs for lipid metabolism. Methods: Eight liver samples were collected from White Large of 70-day fetus (P70) and of 70-day piglets (D70) (with 4 biological repeats at each development period) to construct sRNA libraries. Then the eight prepared sRNA libraries were sequenced using Illumina next-generation sequencing technology on HiSeq 2500 platform. Results: As a result, we obtained 346 known and 187 novel miRNAs. Compared with the D70, 55 down- and 61 up-regulated miRNAs were shown to be significantly differentially expressed (DE). Gene ontology and Kyoto encyclopedia of genes and genomes enrichment analysis indicated that these DE miRNAs were mainly involved in growth, development and diverse metabolic processes. They were predicted to regulate lipid metabolism through adipocytokine signaling pathway, mitogen-activated protein kinase, AMP-activated protein kinase, cyclic adenosine monophosphate, phosphatidylinositol 3 kinase/protein kinase B, and Notch signaling pathway. The four most abundantly expressed miRNAs were miR-122, miR-26a and miR-30a-5p (miR-122 only in P70), which play important roles in lipid metabolism. Integration analysis (details of mRNAs sequencing data were shown in another unpublished paper) revealed that many target genes of the DE miRNAs (miR-181b, miR-145-5p, miR-199a-5p, and miR-98) might be critical regulators in lipid metabolic process, including acyl-CoA synthetase long chain family member 4, ATP-binding casette A4, and stearyl-CoA desaturase. Thus, these miRNAs were the promising candidates for lipid metabolism. Conclusion: Our study provides the main differences in the Large White at miRNA level between two different developmental stages. It supplies a valuable database for the further function and mechanism elucidation of miRNAs in porcine liver development and lipid metabolism.

• Food Science and Preservation
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• v.30 no.4
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• pp.716-728
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• 2023

The anti-adipogenic activity of Glycyrrhiza uralensis was investigated by examining the effects of its ethanol extract (GUE) on a mouse model with a high-fat diet (HFD) and 3T3-L1 preadipocytes during adipocyte differentiation. GUE administration for eight weeks significantly reduced weight gain in mice fed an HFD. GUE effectively inhibited 3T3-L1 preadipocyte differentiation and lipid droplet accumulation. This inhibitory effect is associated with the downregulation of key adipogenic regulators, including PPARγ and C/EBPα, and the modulation of adipose metabolism regulators, such as Fasn and Fabp4. LC-Q-TOF-MS analysis identified twelve phenolic and flavonoid compounds, including liquiritigenin and licorice saponin, in the GUE. These findings demonstrate that the anti-obesity effect of the GUE is attributed to the biological activity of its phenolic and flavonoid compounds. Therefore, the GUE has potential anti-obesity activity. Moreover, further studies on the isolation of bioactive components from the GUE and the investigation of the underlying molecular mechanisms of the GUE are required to establish its efficacy in metabolic disorders, including obesity.

• Journal of Nutrition and Health
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• v.2 no.4
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• pp.113-125
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• 1969

These experiments were designed to study the influence of early protein undernutrition on growth, behaviors toward food, general attitude toward a new environment, brain size and body composition of the experimental rats. The following experimental groups were studied. Lactation period (3 weeks) (Diets of mother rats) 25% Casein diet 12% Casein diet 25% Casein diet 25% Casein diet 12% Casein diet 12% Casein diet After-weaning protein deprivation period None deprivation (25% Casein diet) None deprivation (25% Casein diet) 5% Casein diet (4 weeks) 5% Casein diet (8 weeks) 5% Casein diet (4 weeks) 5% Casein diet (8 weeks) After a long period of rehabilitation with 25% casein diet the following results were obtained. 1. Growth rate during lactation period is closely related with the protein levels of the diet for mother rats. The average body weight of offsprings of the mother rat fed 25% casein diet is 46.0 grams at 21 days old. However, that of the mother rat fed 12% casein diet is only 25.0 grams. 2. The group of protein undernutrition during lactation (S weeks) (offsprings of mother rat fed low protein diet, 12% casein diet) could never catch up with the normal group in its growth even after twenty-four (24) weeks of rehabilitation. 3. However, the groups of protein undernutrition during either four (4) or even eight (8) weeks after weaning could catch up with the normal group in their growth after long period of rehabilitation. 4. The absolute amounts of carcass protein and fat of the normal group are larger than those of the protein deficient groups. In terms of percent carcass, however, the normal group showed higher body fat and lower body protein than the early deficient groups. However, there is no difference between preweaning (3 weeks) and postweaning (8 weeks) deficient groups. It is assumed, from these differences in body composition, that there might be any differences in physiological and metabolic functions among these various groups, and also that the basic formation of various metabolic regulators (protein-nature) might be fixed mostly during lactation and postweaning period. 5. The groups of protein undernutrition during either three (3) weeks lactation or four (4) weeks after weaning are not so remarkably different from the normal group in their amounts of food intake and spillage. However, the groups of undernutrition during either eight (8) weeks postweaning or eleven (11) weeks (3 weeks lactation period plus 8 weeks postweaning period) showed higher amounts of food intake and spillage. In these respects, it seems that desire for food is closely related with the degree of early hunger in protein and also seems that the longer be deficient in early life the more food spillage is found. 6. Both preweaning and postweaning deficient groups showed generally nervous and restless. The normal group is staid and showed less mobilities. 7. The average size of the brains of the group subjected to protein deficiency during three (3) weeks lactation period is smaller than that of the group of the eight (8) weeks postweaning deficiency. This means that the development of the brain is made mostly during lactation period. The group of the eleven (11) weeks postnatal deficiency is significantly different from the normal group in its brain development. It is assumed, in connection with the results of various maze tests reported, that the brain size is closely related with the intellectual ability.

• Toxicological Research
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• v.24 no.4
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• pp.245-251
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• 2008

Dietary restriction (DR) is the most efficacious intervention for retarding the deleterious effects of aging. DR increases longevity, decreases the occurrence and severity of age-related diseases, and retards the physiological decline associated with aging. The beneficial effects of DR have been mostly studied in non-neuronal tissues. However, several studies have showed that DR attenuate neuronal loss after several different insults including exposure to kainate, ischemia, and MPTP. Moreover, administration of the non-metabolizable glucose analog 2-deoxy-D-glucose (2DG) could mimic the neuroprotective effect of DR in rodent, presumably by limiting glucose availability at the cellular level. Based on the studies of chemically induced DR, it has been proposed that the mechanism whereby DR and 2DG protect neurons is largely mediated by stress response proteins such as HSP70 and GRP78 which are increased in neurons of rats and mice fed a DR regimen. In addition, DR, as mild metabolic stress, could lead to the increased activity in neuronal circuits and thus induce expression of neurotrophic factors. Interestingly, such increased neuronal activities also enhance neurogenesis in the brains of adult rodents. In this review, we focus on what is known regarding molecular mechanisms of the protective role of DR in neurodegenerative diseases and aging process. Also, we propose that DR is a mild cellular stress that stimulates production of neurotrophic factors, which are major regulators of neuronal survival, as well as neurogenesis in adult brain.

• Journal of Microbiology and Biotechnology
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• v.18 no.5
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• pp.828-836
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• 2008

The biocontrol rhizobacterium Pseudomonas sp. M18 can produce two kinds of antibiotics, namely pyoluteorin (Plt) and phenazine-1-carboxylic acid (PCA), and is antagonistic against a number of soilborne phytopathogens. In this study, a luxR-type quorum-sensing regulatory gene, vqsR, was identified and characterized immediately downstream of the Plt gene cluster in strain MI8. A vqsR-inactivated mutant led to a significant decrease in the production of Plt and its biosynthetic gene expression. However, this was restored when introducing the vqsR gene by cloning into the plasmid pME6032 in trans. The vqsR mutation did not exert any obvious influence on the production of PCA and its biosynthetic gene expression and the production of N-acylhomoserine lactones (C4 and C8-HSLs) and their biosynthetic gene rhlI expression. Accordingly, these results introduce VqsR as a regulator of Plt production in Pseudomonas spp., and suggest that the regulatory mechanism of vqsR in strain M18 is distinct from that in P. aeruginosa. In addition, it was demonstrated that vqsR mutation did not have any obvious impact on the expression of Plt-specific ABC transporters and other secondary metabolic global regulators, including GacA, RpoS, and RsmA.

• Molecules and Cells
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• v.45 no.4
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• pp.180-192
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• 2022

Nuclear receptor coactivator 6 (NCOA6) is a transcriptional coactivator of nuclear receptors and other transcription factors. A general Ncoa6 knockout mouse was previously shown to be embryonic lethal, but we here generated liver-specific Ncoa6 knockout (Ncoa6 LKO) mice to investigate the metabolic function of NCOA6 in the liver. These Ncoa6 LKO mice exhibited similar blood glucose and insulin levels to wild type but showed improvements in glucose tolerance, insulin sensitivity, and pyruvate tolerance. The decrease in glucose production from pyruvate in these LKO mice was consistent with the abrogation of the fasting-stimulated induction of gluconeogenic genes, phosphoenolpyruvate carboxykinase 1 (Pck1) and glucose-6-phosphatase (G6pc). The forskolin-stimulated inductions of Pck1 and G6pc were also dramatically reduced in primary hepatocytes isolated from Ncoa6 LKO mice, whereas the expression levels of other gluconeogenic gene regulators, including cAMP response element binding protein (Creb), forkhead box protein O1 and peroxisome proliferator-activated receptor γ coactivator 1α, were unaltered in the LKO mouse livers. CREB phosphorylation via fasting or forskolin stimulation was normal in the livers and primary hepatocytes of the LKO mice. Notably, it was observed that CREB interacts with NCOA6. The transcriptional activity of CREB was found to be enhanced by NCOA6 in the context of Pck1 and G6pc promoters. NCOA6-dependent augmentation was abolished in cAMP response element (CRE) mutant promoters of the Pck1 and G6pc genes. Our present results suggest that NCOA6 regulates hepatic gluconeogenesis by modulating glucagon/cAMP-dependent gluconeogenic gene transcription through an interaction with CREB.