• Journal of Life Science
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• v.24 no.5
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• pp.476-484
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• 2014

Obesity, which is characterized by a state of mild chronic inflammation, is known to cause metabolic diseases. This study was carried out to investigate the effect of lyophilized dropwort vinegar powder (DVP) on adipocyte differentiation and inflammation in T3-L1 preadipocyte and RAW 264.7 macrophage cell lines. DVP inhibited the differentiation of 3T3-L1 preadipocytes induced by a mixture of IBMX, dexamethasone, and insulin (MDI). Western blot analysis of cell lysates showed that DVP decreased the levels of two major transcription factors involved in adipogenesis, peroxisome proliferator- activated receptor-${\gamma}$ (PPAR-${\gamma}$) and CCAAT-enhancer-binding protein ${\alpha}$ ($C/EBP{\alpha}$). DVP also significantly suppressed lipopolysaccharide (LPS)-induced production of nitric oxide (NO), and this was accompanied by a decrease in inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) protein expression. These results demonstrate that DVP inhibits MDI-induced adipocyte differentiation of 3T3-L1 cells and LPS-induced inflammation in RAW 264.7 macrophage cells. The findings indicate that this natural product may be a good candidate as to prevent metabolic diseases.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.4067-4073
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• 2012

Obesity is an established risk factor for colorectal cancer. Pioglitazone is a peroxisome proliferator activated receptor$receptor{\gamma}$ ($PPAR{\gamma}$) agonist that induces differentiation in adipocytes and induces growth arrest and/or apoptosis in vitro in several cancer cell lines. In the present study, we investigated the effect of pioglitazone on the development of azoxymethane-induced colon aberrant crypt foci (ACF) in KK-$A^{\mathcal{Y}}$ obesity and diabetes model mice, and tried to clarify mechanisms by which the $PPAR{\gamma}$ ligand inhibits ACF development. Administration of 800 ppm pioglitazone reduced the number of colon ACF/mouse to 30% of those in untreated mice and improved hypertrophic changes of adipocytes in KK-$A^{\mathcal{Y}}$ mice with significant reduction of serum triglyceride and insulin levels. Moreover, mRNA levels of adipocytokines, such as leptin, monocyte chemoattractant protein-1 and plasminogen activator inhibitor-1, in the visceral fat were decreased. PCNA immunohistochemistry revealed that pioglitazone treatment suppressed cell proliferation in the colorectal epithelium with elevation of p27 and p53 gene expression. These results suggest that pioglitazone prevented obesity-associated colon carcinogenesis through improvement of dysregulated adipocytokine levels and high serum levels of triglyceride and insulin, and increase of p27 and p53 mRNA levels in the colorectal mucosa. These data indicate that pioglitazone warrants attention as a potential chemopreventive agent against obesity-associated colorectal cancer.

• Asian-Australasian Journal of Animal Sciences
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• v.31 no.4
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• pp.595-606
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• 2018

Objective: The Fusarium mycotoxins of deoxynivalenol (DON) and zerolenone (ZEN) cause health hazards for both humans and farm animals. Therefore, the main intention of this study was to reveal DON and ZEN effects on the mRNA expression of pro-inflammatory cytokines and other immune related genes in the liver of piglets. Methods: In the present study, 15 six-week-old piglets were randomly assigned to the following three different dietary treatments for 4 weeks: control diet, diet containing 8 mg DON/kg feed, and diet containing 0.8 mg ZEN/kg feed. After 4 weeks, liver samples were collected and sequenced using RNA-Seq to investigate the effects of the mycotoxins on genes and gene networks associated with the immune systems of the piglets. Results: Our analysis identified a total of 249 differentially expressed genes (DEGs), which included 99 upregulated and 150 downregulated genes in both the DON and ZEN dietary treatment groups. After biological pathway analysis, the DEGs were determined to be significantly enriched in gene ontology terms associated with many biological pathways, including immune response and cellular and metabolic processes. Consistent with inflammatory stimulation due to the mycotoxin-contaminated diet, the following Kyoto encyclopedia of genes and genomes pathways, which were related to disease and immune responses, were found to be enriched in the DEGs: allograft rejection pathway, cell adhesion molecules, graft-versus-host disease, autoimmune thyroid disease (AITD), type I diabetes mellitus, human T-cell leukemia lymphoma virus infection, and viral carcinogenesis. Genome-wide expression analysis revealed that DON and ZEN treatments downregulated the expression of the majority of the DEGs that were associated with inflammatory cytokines (interleukin 10 receptor, beta, chemokine [C-X-C motif] ligand 9), proliferation (insulin-like growth factor 1, major facilitator superfamily domain containing 2A, insulin-like growth factor binding protein 2, lipase G, and salt inducible kinase 1), and other immune response networks (paired immunoglobulin-like type 2 receptor beta, Src-like-adaptor-1 [SLA1], SLA3, SLA5, SLA7, claudin 4, nicotinamide N-methyltransferase, thyrotropin-releasing hormone degrading enzyme, ubiquitin D, histone $H_2B$ type 1, and serum amyloid A). Conclusion: In summary, our results demonstrated that high concentrations DON and ZEN disrupt immune-related processes in the liver.

• Clinical and Experimental Reproductive Medicine
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• v.26 no.3
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• pp.331-338
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• 1999

The purposes of this study were to evaluate the effects of insulin-like growth factor (IGF)s in peritoneal fluid (PF) from patients with and without endometriosis on the proliferation of endometrial stromal cells and to investigate the effects of type I IGF receptor antibody on the response of endometrial stromal cells to PF from patients with endometriosis. IGFs in PF from patients with endometriosis (n=14) and without endometriosis (n=10) were measured by immunoradiometric assay and PF samples were divided into low IGF-I PF group (less than 85 ng/ml) and high IGF-I PF group (more than 85 ng/ml). Endometrial stromal cells from patients without endometriosis were cultured in serum free media in the presence or absence of 1 % PF and thymidine incorporation test were used to evaluate the proliferation of endometrial stromal cells. Also cultures were incubated with type I IGF receptor monoclonal antibody (${\alpha}IR_3$) before adding PF. PF from patients with endometriosis and without endometriosis increased thymidine incorporation in endometrial stromal cells. In patients with endometriosis, high IGF-I PF group had high IGF-II levels and resulted in higher thymidine incorporation than low IGF-I PF group but no significant difference in increase in thymidine incorporation between high IGF-I and low IGF-I PF group was noted in patients without endometriosis. There was not a significant correlation between increase in thymidine incorporation and IGF-I levels in PF from patients without endometriosis but in PF from patients with endometriosis. Preincubation with ${\alpha}IR_3$ significantly inhibited the mitogenic response of endometrial stromal cells to PF. Our data indicate that IGF-I in PF may be involved in the growth of ectopic endometrium in patients with endometriosis.

• The Journal of the Korea Contents Association
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• v.9 no.4
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• pp.355-363
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• 2009

Increased oxidative stress by abnormal mitochondrial function can damage cell signal transduction and gene expression, and induce insulin resistance or diabetes. Autophagy, however, improve insulin resistance by clearance of malfunctioning mitochondria. Exercise also recovers the muscle dysfunction and degeneration by activating mitochondrial biogenesis. As it seems that exercise and autophagy might act as an orchestrated network to induce mitochondrial biogenesis, we investigated whether autophagy is involved in AMPK signal pathway stimulated by exercise or AICAR to increase mitochondrial biogenesis. And it showed that PGC-1 and mtTFA, but not autophagy marker LC3 mRNA expression were significantly increased by 6 hr of acute exercise. On the other hand, PGC-1 and mtTFA mRNA expression were upregulated by AICAR treatment to C2C12 myotube. However these genes were not inhibited by LC3 siRNA transfection. These results provide the evidence that autopahgy affects on mitochondrial biogenesis through different signal pathway from AMPK signal transduction.

• Asian-Australasian Journal of Animal Sciences
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• v.14 no.3
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• pp.307-315
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• 2001

Litter size has been one of the important economic traits in porcine reproduction. The insulin-like growth factor (IGF) system has been shown to mediate actions of the steroid hormone or to synergize with other endocrine factors so that it consequently plays roles in reproductive processes, including ovulation, implantation, maintenance of pregnancy, and fetal development. However, the effect of the serum IGF system on porcine litter size has not been deeply studied. Therefore, this study was conducted to relate serum IFG-II concentration and IGF binding protein-3 (IGFBP-3) expression with porcine litter size. Moreover, the possible association of those with estrogen receptor (ER) as a candidate gene for litter size was investigated. Swine were separated into two groups showing high and low litter sizes, and sera were collected from sows in the estrous cycle to postnatal growth of their female progeny. Serum IFG-II concentration was measured by radioimmunoassay and IGFBP-3 expression was detected by Western ligand blotting. During the estrous cycle, IGFBP-3 expression in both groups decreased moderately from metestrus to estrus, but IFG-II concentration showed a reverse pattern. Also, IFG-II concentration and IGFBP-3 expression decreased gradually as pregnancy proceeded. Unlike IGFBP-3, IFG-II decreased moderately as newborn pigs grew. Significant differences in serum IFG-II amount between the two groups were detected at 60 (p<0.01), 75, 90, and 105 d (p<0.05) of pregnancy and at 60 (p<0.01), 45, and 105 d (p<0.05) of postnatal growth. Furthermore, based on ER genotypes, a high litter size group with genotypes AB and BB showed lower IFG-II concentration than a low litter size group with a genotype AA during pregnancy. Taken together, the results indicate that the serum IFG-II and IGFBP-3 are correlated with the litter size in pigs.

• Journal of Korean Medicine for Obesity Research
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• v.13 no.2
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• pp.74-83
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• 2013

Objectives: This study was performed to evaluate the effects of fermented lotus extracts on the inhibition of differentiation in 3T3-L1 preadipocytes. Methods: Extracts of lotus leaf and lotus root were fermented using 4 different probiotics separately, including Lactobacillus plantarum, Lactobacillus rhamnosus, Bifidobacterium breve, and Bifidobacterium longum. Inhibition of preadipocyte differentiation was examined by Oil red O dye staining. Expressions of adipogenic transcription factors including CCAAT/enhancer binding proteins (C/$EBP{\alpha}$) and peroxisome proliferators-activated receptor ${\gamma}$ ($PPAR{\gamma}$) were analyzed by real time polymerase chain reaction and Western blotting analysis. Results: Fermented lotus extracts inhibited adipogenic transcription factors by inhibiting preadipocytes differentiation. All of the groups fermented by 4 kinds of probiotics showed reduction in Oil Red O dye staining. Bifidobacterium breve showed the most effective inhibition of C/$EBP{\alpha}$. Bifidobacterium breve and Bifidobacterium longum showed the best downregulation of $PPAR{\gamma}$ expressions compared with the control and the unfermented lotus group. Conclusions: Fermented lotus extracts showed significant effects on inhibition of preadipocyte differentiation in 3T3-L1 preadipocytes showing correlation with insulin sensitivity and lipid metabolism related with obesity.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.21 no.2
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• pp.111-117
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• 2018

Purpose: The prevalence of obesity has significantly increased among children and adolescents worldwide and is becoming an important health care problem in parallel with the increased prevalence of obesity pediatric non-alcoholic fatty liver disease. Betatrophin is a newly define hormone that is commonly secreted by liver and plays role in glucose tolerance. This study aimed to investigate the relationship between serum betatrophin levels and non-alcoholic fatty liver disease in obese children. Methods: The study included 40 obese children with a body mass index (BMI) above 95th centile, and 35 non-obese subjects with a BMI 3-85th centile, whose age and gender were similar to those of the patient group. For the evaluation of metabolic parameters fasting serum glucose, insulin, alanine aminotransferase, aspartate aminotransferase, lipid profile and serum betatrophin levels were measured. Total cholesterol: high-density lipoprotein cholesterol and low-density lipoprotein cholesterol: high-density lipoprotein cholesterol ratios were calculated as "atherogenic indices." Results: Serum betatrophin levels of the obese subjects were similar to that of non-obese subjects (p=0.90). Betatrophin levels were not correlated with the metabolic parameters. Conclusion: In the present study, levels of betatrophin are not different between obese and insulin resistant children and non-obese subjects, and they are not correlated with atherogenic indices. To elucidate the exact role of betatrophin in obesity, further studies are required to identify the betatrophin receptor and/or other possible cofactors.

• Nutrition Research and Practice
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• v.9 no.6
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• pp.628-636
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• 2015

BACKGROUND/OBJECTIVES: Obesity is a risk factor of breast cancer in postmenopausal women. Estrogen deprivation has been suggested to cause alteration of lipid metabolism thereby creating a cellular microenvironment favoring tumor growth. The aim of this study is to investigate the effects of estrogen depletion in combination with excess energy supply on breast tumor development. MATERIALS/METHODS: Ovariectomized (OVX) or sham-operated C3H/HeN mice at 4 wks were provided with either a normal diet or a high-fat diet (HD) for 16 weeks. Breast tumors were induced by administration of 7,12-dimethylbenz(a)anthracene once a week for six consecutive weeks. RESULTS: Study results showed higher serum concentrations of free fatty acids and insulin in the OVX+HD group compared to other groups. The average tumor volume was significantly larger in OVX+HD animals than in other groups. Expressions of mammary tumor insulin receptor and mammalian target of rapamycin proteins as well as the ratio of pAKT/AKT were significantly increased, while pAMPK/AMPK was decreased in OVX+HD animals compared to the sham-operated groups. Higher relative expression of liver fatty acid synthase mRNA was observed in OVX+HD mice compared with other groups. CONCLUSIONS: These results suggest that excess energy supply affects the accelerated mammary tumor growth in estrogen deprived mice.

• Asian-Australasian Journal of Animal Sciences
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• v.19 no.10
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• pp.1508-1513
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• 2006

Myostatin (MSTN) and insulin-like growth factors (IGFs) are a known inhibitor and stimulators of proliferation and differentiation of muscle cells, respectively. The present study was performed to investigate the relationship of MSTN-induced growth inhibition to expression of the IGF system components and myogenin, a muscle cell-specific transcription factor, in rat L6 myoblasts. The L6 cells transfected with a green fluorescent protein-MSTN plasmid expression construct had a 47% less cell number than mock-transfected cells after 3-d serum-free culture, accompanied by delayed differentiation which was suggested by inhibited aggregation of cells. Moreover, cells transfected with the expression construct had decreased expression of IGF-II and myogenin genes, but not IGF-I or its receptor genes, as examined by reverse transcription-polymerase chain reaction. The reduced mitosis of the L6 cells transfected with the MSTN-expression construct increased following an addition of either IGF-I or IGF-II to the culture medium, but not to the level of mock-transfected cells. By contrast, myogenin gene expression in these cells increased after the addition of either IGF to the level of mock-transfected cells. Collectively, these results suggest that the inhibitory effect of MSTN on L6 cell proliferation and differentiation is likely to be partly mediated by serially suppressed expression of IGF-II and myogenin genes, not IGF-I gene.