• Molecular & Cellular Toxicology
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• v.5 no.4
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• pp.298-303
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• 2009

(-)-Epigallocatechin-3-gallate (EGCG), a major flavonoid in green tea has multiple health benefits including chemoprevention, anti-inflammatory, anti-diabetic, and anti-obesity effects. In connection with these effects, EGCG can be a candidate to help the treatment of metabolic diseases. Metformin is a widely used anti-diabetic drug regulating cellular energy homeostasis via AMP-activated protein kinase (AMPK) activation. Therefore, the combination of metformin with EGCG may have additive or synergistic effects on treatment of type 2 diabetes. Nevertheless, there is no report for the pharmacokinetic and/or pharmacodynamic interaction of EGCG with metformin. Here, we evaluated the pharmacokinetic and pharmacodynamic interaction between metformin and EGCG in rats. Pharmacokinetics parameters of metformin were measured after oral administration of metformin in rats pre-treated with EGCG (10 mg/kg) or saline for 7 days. The results showed that there is no significant difference in pharmacokinetic parameters between saline control and EGCG-treated group. In addition, the hepatic AMPK activation by metformin in EGCG-treated rats was also similar to the control. The lack of additive effects of EGCG on AMPK activation or intracellular uptake of metformin was also evaluated in cells in the presence or absence of EGCG. Treatment of HepG2 cells with EGCG inhibited the metformin-induced AMPK activation. Combined results suggested that EGCG has no effect on the pharmacokinetics of metformin but may contribute to metformin action.

• Journal of the East Asian Society of Dietary Life
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• v.19 no.5
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• pp.713-722
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• 2009

Vitamin D levels have been reported to be associated with diabetes, obesity and metabolic syndrome. There have been studies on the nutritional status of vitamin D in postmenopausal women at Seoul and premenopausal women at Busan, and these studies showed that nearly no relationship between serum vitamin D levels and the obesity index existed. However, there have been no studies that examined about the relationship between serum vitamin D levels and insulin resistance in Korea. In this study, we investigated serum vitamin D levels and the relationship between serum vitamin D levels and insulin resistance (homeostasis model assessment of insulin resistance), obesity index (body mass index, percentage of body fat and waist circumference) in 180 premenopausal women (non-obese women 87.8%, obese women 12.2%) in spring (March~April), fall (September~October) and winter (January~February) at Daejeon. Serum vitamin D levels were lower in winter than in spring-fall, after adjusting for age and the obesity index. The frequency of vitamin D inadequacy (serum vitamin D levels were $\leq$ 20 ng/mL) was 45.5% in winter and, 23.5% in spring-fall, and which showed that vitamin D inadequacy was higher in winter than in spring-fall. Multiple regression analysis showed that serum vitamin D levels had no relationship with the obesity index or insulin resistance. There was no difference in the obesity index or insulin resistance between the vitamin D inadequacy and normal group, and there was no relationship between serum vitamin D levels and the obesity index or insulin resistance in non-obese and obese premenopausal women, respectively. In conclusion, serum vitamin D levels in premenopausal women at Daejeon were lower in winter than in spring-fall, and the frequency of vitamin D inadequacy was higher in winter than in spring-fall. Serum vitamin D levels had no relationship with the obesity index or insulin resistance in premenopausal women, most of whom were not obese.

• Asian-Australasian Journal of Animal Sciences
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• v.31 no.1
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• pp.138-148
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• 2018

Objective: Fusarium mycotoxins deoxynivalenol (DON) and zearalenone (ZEN), common contaminants in the feed of farm animals, cause immune function impairment and organ inflammation. Consequently, the main objective of this study was to elucidate DON and ZEN effects on the mRNA expression of pro-inflammatory cytokines and other immune related genes in the kidneys of piglets. Methods: Fifteen 6-week-old piglets were randomly assigned to three dietary treatments for 4 weeks: control diet, and diets contaminated with either 8 mg DON/kg feed or 0.8 mg ZEN/kg feed. Kidney samples were collected after treatment, and RNA-seq was used to investigate the effects on immune-related genes and gene networks. Results: A total of 186 differentially expressed genes (DEGs) were screened (120 upregulated and 66 downregulated). Gene ontology analysis revealed that the immune response, and cellular and metabolic processes were significantly controlled by these DEGs. The inflammatory stimulation might be an effect of the following enriched Kyoto encyclopedia of genes and genomes pathway analysis found related to immune and disease responses: cytokine-cytokine receptor interaction, chemokine signaling pathway, toll-like receptor signaling pathway, systemic lupus erythematosus (SLE), tuberculosis, Epstein-Barr virus infection, and chemical carcinogenesis. The effects of DON and ZEN on genome-wide expression were assessed, and it was found that the DEGs associated with inflammatory cytokines (interleukin 10 receptor, beta, chemokine [C-X-C motif] ligand 9, CXCL10, chemokine [C-C motif] ligand 4), proliferation (insulin like growth factor binding protein 4, IgG heavy chain, receptor-type tyrosine-protein phosphatase C, cytochrome P450 1A1, ATP-binding cassette sub-family 8), and other immune response networks (lysozyme, complement component 4 binding protein alpha, oligoadenylate synthetase 2, signaling lymphocytic activation molecule-9, ${\alpha}$-aminoadipic semialdehyde dehydrogenase, Ig lambda chain c region, pyruvate dehydrogenase kinase, isozyme 4, carboxylesterase 1), were suppressed by DON and ZEN. Conclusion: In summary, our results indicate that high concentrations of DON and ZEN suppress the inflammatory response in kidneys, leading to potential effects on immune homeostasis.

• Analytical Science and Technology
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• v.30 no.6
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• pp.355-378
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• 2017

Because neurochemicals are related to homeostasis and cognitive and behavioral functions in human body and because they enable the diagnosis of numerous neurodegenerative disorders, there has been increasing interest in the development of analytical platforms for neurochemical profiling in biological samples. In particular, mass spectrometry (MS)-based analytical methods combined with chromatographic separation have been widely used to profile neurochemicals in metabolic pathways. However, development of delicate sample preparation procedures and highly sensitive instrumental detection is necessary considering the trace levels and chemical instabilities of neurochemicals in biological samples. Therefore, in this review, analytical trends in MS-based metabolomics approaches to neurochemicals in multiple biological samples, such as urine, blood, CSF, and biological tissues, are discussed. This paper is expected to contribute to the development of an analytical platform to discover biomarkers that will aid diagnosis, prognosis, and treatment of neurodegenerative disorders.

• Journal of Life Science
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• v.30 no.11
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• pp.1021-1032
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• 2020

Numbers of companion animals and people rearing them are increasing in developed countries. As a result, businesses related to companion animals are becoming more advanced and specialized. Dogs have been cohabiting with humans as companions (pets) for thousands of years and, as a result, eat carbohydrate-rich foods similar to humans and maintain lives similar to their owners. Tight bonds between dogs and their owners are formed by sharing similar lifestyles, including a dwelling and food. Owners are responsible for their pets and treat them with emotional stability. Pets depend on their owners, although the food situation can cause stress. Since pet dogs are carnivorous in nature, providing pet dogs with a nutritionally balanced diet and functional materials is important for a healthy gut microbiome. Recently, the gut microbiota has become a research focus because it is associated with protection from harmful pathogens and immune regulation while maintaining physiological homeostasis. An abnormal gut microbiota is related to pathogenic processes and various gut, metabolic, mental, and neurological diseases. Additionally, pet dogs at risk of disease affect the health of their owners. Therefore, this review discusses the composition and diversity of the gut microbiota of dogs and the relationships between the gut microbiota and diseases.

• The Korea Journal of Herbology
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• v.32 no.1
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• pp.15-23
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• 2017

Objectives : It is well known that Sibjotang (Shizaotang), traditional herbal medicine formula, regulates the body fluid blood pressure homeostasis. This study is to investigate whether Sibjotang improves diabetic renal dysfunction in type II diabetes mellitus animal model, db/db mice. Methods : The animals model were divided into three groups at the age of 8 weeks; control group (C57BLKS/J-db/m mice), diabetic group [(C57BLKS/J+Lepr)-db/db mice], and Sibjotang group [(C57BLKS/J+Lepr)-db/db mice + Sibjotang 100 mg/kg/day]. During 8 weeks of treatment, blood glucose and urinary albumin excretion were checked in metabolic chamber at 8, 12, and 16 weeks of age, respectively. Results : Body weight and food intake of diabetic group were significantly higher than control group after 8 weeks administration. However, there were not significant different between the diabetic group and Sibjotang group. Urinary albumin excretion was significantly decreased in the Sibjotang group than the diabetic group. In addition, supplementation with Sibjotang significantly lowered levels of blood glucose, insulin, and homeostatic model assessment-insulin resistance (HOMA-IR), suggesting reduced insulin resistance. The ratio of mesangial matrix/glomerular area was markedly larger in diabetic group than control group, whereas Sibjotang significantly reduced this expansion. Moreover, immunohistological study revealed that Sibjotang attenuated the increase of transforming growth $factor(TGF)-{\beta}$ expression in kidney. Conclusion : Sibjotang ameliorates diabetes-associated renal injury through the improvement of the blood glucose and insulin sensitivity, and inhibiting the $TGF-{\beta}1$ expression. Therefore, Sibjotang may be a new therapeutic formula for the treatment of diabetic-associated renal dysfunction.

• The Korean Journal of Physiology and Pharmacology
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• v.20 no.5
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• pp.459-466
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• 2016

Adipogenic differentiation of mesenchymal stem cells (MSCs) is critical for metabolic homeostasis and nutrient signaling during development. However, limited information is available on the pivotal modulators of adipogenic differentiation of MSCs. Adaptor protein Lnk (Src homology 2B3 [SH2B3]), which belongs to a family of SH2-containing proteins, modulates the bioactivities of different stem cells, including hematopoietic stem cells and endothelial progenitor cells. In this study, we investigated whether an interaction between insulin-like growth factor-1 receptor (IGF-1R) and Lnk regulated IGF-1-induced adipogenic differentiation of MSCs. We found that wild-type MSCs showed greater adipogenic differentiation potential than $Lnk^{-/-}$ MSCs. An ex vivo adipogenic differentiation assay showed that $Lnk^{-/-}$ MSCs had decreased adipogenic differentiation potential compared with wild-type MSCs. Interestingly, we found that Lnk formed a complex with IGF-1R and that IGF-1 induced the dissociation of this complex. In addition, we observed that IGF-1-induced increase in the phosphorylation of Akt and mammalian target of rapamycin was triggered by the dissociation of the IGF-1R-Lnk complex. Expression levels of a pivotal transcription factor peroxisome proliferator-activated receptor gamma ($PPAR-{\gamma}$) and its adipogenic target genes (LPL and FABP4) significantly decreased in $Lnk^{-/-}$ MSCs. These results suggested that Lnk adaptor protein regulated the adipogenesis of MSCs through the $IGF-1/Akt/PPAR-{\gamma}$ pathway.

• Journal of Nutrition and Health
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• v.7 no.2
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• pp.37-51
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• 1974

This Study was carried out to observe the effect of nutritional condition on the change of protein metabolism in the animal body by feeding on imbalanced protein diet. A total 242 growing male albino rats, weighing $115{\sim}120$ gm, were used for the experimental animals. The rats were fed on the standard diet(st), protein flee diet(pf) and imbalanced protein diet(ib) for twelve weeks respectively. Hemoglobin, packed cell volume in blood, and total nitrogen, amino acid nitrogen, urea-nitrogen, creatinine, transaminases(GPT, GOT) in liver and serum, and total nitrogen in small intestine, and total nitrogen, urea-nitrogen In small intestine, and total nitrogen, urea-nitrogen, creatinine, urea-nitrogen/creatinine ratio in urine were measured. The results obtained are as follows; 1. The gained body weight were lower in pf group and ib group than those of st group. The gained body weight fed for 12 weeks, were 80% lower in pf group than those of st group, and the body weight of pf group for $50{\sim}75$ days feeding were $40{\sim}60%$ decreased, compared with the stating weight, and then all of them died. 2. The change of the brain, liver, kidney, spleen and small intestine by feeding on imbalanced diet for 12 weeks were no remarkable difference with the starting weight, but those of protein free diet group were half or more decrease and those were significantly lower in spleen and small intestine especially than the other organ 3. The contents of hemoglobin in pf group for 8 weeks feeding, and the packed cell volume in pf group for 8 weeks feeding and in ib group for 12 weeks feeding were decreased. but those of the other feeding group were almost same value. 4. The total nitrogen in the liver, small intestine and serum of each diet group were no remarkable difference respectively. The contents of amino acid nitrogen in pf group for 2 and 6 weeks feeding were increased. 5. On transaminases: a) The cycle of increase and decrease of GPT activities were come periodically and the interval of cycle were fast in the early stage of feeding and slow there-after. b) The GPT activities were decreased gradually in pf group after feeding and those were increased in ib group for 6 weeks feeding but decreased there-after. The frequency of cycle were more GPT than GOT and specially those of GPT in early stage of feeding were two or three times while GOT was one. c) The interval of increase and decrease in GOT and amino acid nitrogen cycle were similar tendency. 6. The contents of total nitrogen, creatinine and urea-nitrogen of pf group in urine were decreased very sharply from sharting feeding to one week but increased dully from six weeks to eight weeks feeding. The contents of urea-nitrogen of ib group were increased dully by feeding on ten weeks but decreased by feeding on twelve weeks. From the above results, it is concluded that the trend of the metabolic change is maintained equally by homeostatic mechanism using the endogenous protein source during a certain period by imbalanced protein diet feeding. The homeostatic mechanism is come peridically, very fast in early stage of feeing and than slow there-after.

• Korean Journal of Poultry Science
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• v.46 no.3
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• pp.185-191
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• 2019

Nucleoporin 210 (Nup210) is associated with several physiological processes including muscle and neural cell differentiation, autoimmune diseases, and peripheral T cell homeostasis. Chicken Nup210 (chNup210) gene was originally identified as one of the differentially expressed genes (DEGs) in the kidney tissues of chicken. To elucidate the role of Nup210 in metabolic disease of chicken, we studied the molecular characteristics of chNup210 and analyzed its gene expression under the stimulation of Toll-like receptor 3 (TLR3) ligands. The Nup210 genomic DNA and amino acid sequences of various species including fowls, fishes, and mammals were retrieved from the Ensemble database and subjected to bioinformatics analyses. The expression of Nup210 from several chicken tissues was probed through qRT-PCR, and chicken fibroblast DF-1 cell line was used to determine the change in expression of chNup210 after stimulation with TLR3 ligand, polyinosinic-polycytidylic acid (poly (I:C)). The chNup210 gene was highly expressed in chicken lung and spleen tissues. Although highly conserved among the species, chNup210 was evolutionary clustered in the same clade as that of duck compared to other mammals. Furthermore, this study revealed that chNup210 is expressed in TLR3 signaling pathway and provides fundamental information on Nup210 expression in chicken. Future studies that offer insight into the involvement of chNup210 in the chicken innate immune response against viral infection are recommended.

• Journal of Life Science
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• v.32 no.1
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• pp.63-69
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• 2022

The thioredoxin reductase (TrxR) system is essential for cell survival and function by playing a pivotal role in maintaining homeostasis of cellular redox and regulating signal transduction pathways. The TrxR system comprises thioredoxin (Trx), TrxR, and nicotinamide adenine dinucleotide phosphate. Trx reduced by the catalytic reaction of the TrxR enzyme reduces downstream proteins, resulting in protection against oxidative stress and regulation of cell differentiation, growth, and death. Cancer cells survive by improving their intracellular antioxidant capacity to eliminate excessively generated reactive oxygen species (ROS) due to infinite cell proliferation and a high metabolic rate. Therefore, cancer cells have high dependence and sensitivity to antioxidant systems, suggesting that focusing on TrxR, a representative antioxidant system, is a potential strategy for cancer therapy. Several studies have revealed that TrxR is expressed at high levels in various types of cancers, and research on anticancer activity targeting the TrxR system is increasing. In this review, we discuss the feasibility and value of the TrxR system as a strategy for anticancer activity research by examining the relationship between the function of the intracellular TrxR system and the development and progression of cancer, considering the anticancer activity and mechanism of TrxR inhibitors.