• Proceedings of the Korean Nutrition Society Conference
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• 1995.11b
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• pp.11-34
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• 1995

Growth hormone (GH) plays a key role in regulating postnatal growth and can stimulate growth of animals by acting directly on specific receptors on the plasma membrane of tissues or indirectly through stimulating insulin-like growth factor (IGF)-I synthesis and secretion by the liver and other tissues. IGF-I and IGF-Ⅱ are polypeptides with structural similarity with proinsulin that stimulate cell proliferation by endocrine, paracrine and autocrine mechanisms. The initial event in the metabolic action of IGFs on target cells appears to be their binding to specific receptors on the plasma membrane. Current evidence indicates that the mitogenic actions of both IGFs are mediated primarily by binding to the type I IGF receptors, and that IGF action is also mediated by interactions with IGF-binding proteins (IGFBPs). Six distinct IGFBPs have been identified that are characterized by cell-specific interaction, transcriptional and post-translational regulation by many different effectors, and the ability to either potentiate or inhibit IGF actions. Nutritional deficiencies can have their devastating consequence during growth. Although IGF-I is the major mediator of GH's action on somatic growth, nutritional status of an organism is a critical regulator of IGF-I and IGFBPs. Various nutrient deficiencies result in decreased serum IGF-I levels and altered IGFBP levels, but the blood levels of GH are generally unchanged or elevated in malnutrition. Effects of protein, energy, vitamin C and D, and zinc on serum IGF and IGFBP levels and tissue mRNA levels were reviewed in the text. Multiple factors are involved in the regulation of intestinal epithelial cell growth and differentiation. Among these factors the nutritional status of individuals is the most important. The intestinal epithelium is an important site for mitogenic action of the IGFs in vivo, with exogenous IGF-I stimulating mucosal hyperplasia. Therefore, the IGF system appears to provide and important mechanism linking nutrition and the proliferation of intestinal epithelial cells. In order to study the detailed mechanisms by which intestinal mucosa is regulated, we have utilized IEC-6 cells, an intestinal epithelial cell line and Caco-2 cells, a human colon adenocarcinoma cell line. Like intestinal crypt cells analyzed in vivo or freshly isolated intestinal epithelial cells, IEC-6 cells and Caco-2 cells possess abundant quatities of both type Ⅰ and type Ⅱ IGF receptors. Exogenous IGFs stimulate, whereas addition of IGFBP-2 inhibits IEC-6 cell proliferation. To investigate whether endogenously secreted IGFBP-2 inhibit proliferation, IEC-6 cells were transfected with a full-length rat IGFBP-2 cDNA anti-sense expression construct. IEC-6 cells transfected with anti-sense IGFBP-2 protein in medium. These cells grew at a rate faster than the control cells indicating that endogenous IGFBP-2 inhibits proliferation of IEC-6 cells, probably by sequestering IGFs. IEC-6 cells express many characteristics of enterocyte, but do not undergo differentiation. On the other hand, Caco-2 cells undergo a spontaneous enterocyte differentiation. On the other hand, Caco-2 cells undergo a spontaneous enterocyte differentiation after reaching confluency. We have demonstrated that Caco-2 cells produce IGF-Ⅱ, IGFBP-2, IGFBP-3, and an as yet unidentified 31,000 Mr IGFBP, and that both mRNA and peptide secretion of IGFBP-2 and IGFBP-3 increased, but IGFBP-4 mRNA and protein secretion decreased after the cells reached confluency. These changes occurred in parallel to and were coincident with differentiation of the cells, as measured by expression of sucrase-isomaltase. In addition, Caco-2 cell clones forced to overexpress IGFBP-4 by transfection with a rat IGFBP-4 cDNA construct exhibited a significantly slower growth rate under serum-free conditions and had increased expression of sucrase-isomaltase compared with vector control cells. These results indicate that IGFBP-4 inhibits proliferation and stimulates differentiation of Caco-2 cells, probably by inhibiting the mitogenic actions of IGFs.

• Journal of Korean Society of Environmental Engineers
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• v.31 no.11
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• pp.947-956
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• 2009

Residual petroleum hydrocarbons after an oil spill may accumulate in the marine benthic ecosystem due to their high hydrophobicity. A lot of monitoring data are required for the estimation of ecosystem exposure to residual petrochemicals in an ecological risk assessment in the affected region. To save time and cost, the environmental exposure to them in the affected ecosystem can also be assessed using a simple food-web bioaccumulation model. In this study, we evaluated residual concentrations of four selected polycyclic aromatic hydrocarbons (phenanthrene, anthracene, pyrene, and benzo[a]pyrene) in a hypothetic benthic ecosystem composed of six species under two exposure scenarios. Body-residue concentration ranged 5~250 mg/kg body depending on trophic positions in an extreme scenario in which the aqueous concentrations of PAHs were assumed to be one-tenth of their aqueous solubility. In addition, bioconcentration factors (BCFs) and bioaccumulation factors (BAFs) were evaluated for model species. The logarithm of bioconcentration factor (log BCF) linearly increased with increasing the logarithm of 1-octanol-water partition coefficient (log $K_{OW}$) until log $K_{OW}$ of 7.0, followed by a gradual decrease with further increase in log $K_{OW}$ without metabolic degradation. Biomagnification became significant when log $K_{OW}$ of a pollutant exceeded 5.0 in the model ecosystem, indicating that investigation of food-web structure should be critical to predict biomagnifications in the affected ecosystem because log $K_{OW}$ values of many petrochemicals are higher than 5.0. Although further research is required for better site-specific evaluation of exposure, the model simulation can be used to estimate the level of the ecosystem exposure to residual oil contaminants at the screening level.

• Clinical and Experimental Pediatrics
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• v.49 no.1
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• pp.34-39
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• 2006

Purpose : The incidence of neonatal hyperbilirubinemia is twice as high in East Asians as in Caucasians. However, its metabolic basis has not been clearly explained. The UDP-glucuronosyltransferase gene(UGT1A1) mutation was found to be a risk factor of neonatal hyperbilirubinemia. We studied whether neonatal hyperbilirubinemia is associated with the 1828G>A(rs 10929303) polymorphism of the UGT1A1 gene, which encodes for a key enzyme of bilirubin metabolism. Methods : The genomic DNA was isolated from 80 Korean full term neonates who had greater than a 12 mg/dL level of serum bilirubin with no obvious cause, and the genomic DNA was also isolated from 164 Korean neonates of the control population. We studied a single nucleotide polymorphism (SNP) of 1828G>A in the untranslated region of the UGT1A1 gene by direct sequencing. Results : Three of the 80 neonates with a serum bilirubin level above 12 mg/dL had homozygous mutations and 10 of the 80 neonates with a serum bilirubin level above 12 mg/dL had heterozygous mutations. Thirteen of the 164 neonates of the control group had homozygous mutations and 16 neonates of the control group had heterozygous mutations. The allele frequency of 1828G>A polymorphism of UGT1A1 in the hyperbilirubinemia group was 10.0 percent, which was not significantly different from the allele frequency of 12.8 percent in the control group. Conclusion : In this study, the 1828G>A polymorphism of the UGT1A1 gene was detected in the Korean neonates with neonatal hyperbilirubinemia. Our results indicated that this SNP is not associated with the prevalence of hyperbilirubinemia in Koreans.

• Journal of Nutrition and Health
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• v.40 no.8
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• pp.719-727
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• 2007

To elucidate the relationship among the levels of nutrients intake, bone mineral density(BMD) and the urinary biochemical markers of bone metabolism, this survey is conducted with 225 postmenopausal women over 50 years of age. The urinary biochemical markers including deoxypyridinoline(DPD) and Ca excretion were measured. Bone mineral densities of lumbar spine(L2-L4), femoral neck, ward's triangle and trochanter were measured with dual-energy X-ray absorptiometry and the nutrient intake data obtained by 24 hr recall method. Mean age of all subjects was 64.8 years old, and the BMDs of the subjects were $0.86g/cm^2$(lumbar spine), $0.60g/cm^2$(femoral neck), $0.49g/cm^2$(trochanter), and $0.41g/cm^2$(ward's triangle). The results were compared among 3 groups with different nutrient intake levels classified by the percentage of Dietary Reference Intakes(DRIs) for Koreans as follows: low < 75% DRIs, 75% DRI $\leq$ adequate < 125% DRIs, high $\geq$ 125% DRIs. Bone mineral density of adequate protein intake group was significantly higher than those of low and high protein intake groups(p<0.05). Urinary DPD excretion was lowest in protein and calcium adequate intake groups(p<0.05, p<0.05), respectively. In relation to urinary Ca excretion, it is revealed to be considerably lower in the groups taking protein and vitamin C adequate intake(p<0.05, p<0.05). The percent DRI of protein and calcium were positively correlated with the BMD of the femoral neck after adjusted age(p<0.05, p<0.05). These results showed that there are probably some relationships between nutrient intake levels and urinary biochemical markers. For postmenopausal women with adequate nutrition expecially protein, calcium and vitamin C, has an important role to postpone bone resorption and to prevent the decrease of bone density.

• Tuberculosis and Respiratory Diseases
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• v.39 no.1
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• pp.42-54
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• 1992

Background:It has been suggested that the cyclooxygenase metabolites play an important role in changes of early hemodynamic parameters in the endotoxin-induced acute lung injury. But there have been many debates about their role in the late increase of alveolar-capillary permeability, and it is not known whether they act directly or indirectly through oxygen free radicals which have been known to be produced during the metabolic process of cyclooxygenase pathway. So we performed this study to identify the pathogenetic role of cyclooxygenase metabolites in the endotoxin-induced acute lung injury in domestic pigs. Method: We infused endotoxin into 8 domestic pigs; endotoxin only (n=3), and pretreatment with indomethacin (n=5). We observed the sequential changes in hemodynamic parameters, the concentration of plasma oxidized glutathione (GSSG) in pulmonary arterial and venous blood, and albumin content in bronchoalveolar lavage fluid (BALF). Results: 1) While cardiac output decreased, mean pulmonary arterial pressure, pulmonary vascular resistance, and alveolar-arterial oxygen difference increased over phase 1 (0-2hr) and phase 2 (2-4.5hr) by endotoxin, indomethacin attenuated the decrease in cardiac output during phase 1 and increase in mean pulmonary arterial pressure, pulmonary vascular resistance, and alveolar-arterial oxygen difference during both phases. 2) The increase in plasma GSSG content during phase 2 was not attenuated by indomethacin. 3) The content of BALF albumin was significantly lower in indomethacin groups than that of endotoxin group. Conclusion: These results suggest that it is likely that cyclooxygenase metabolites have an effect on endotoxin-induced acute lung injury during both phases probably through direct action.

• Journal of the Korean Society of Food Science and Nutrition
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• v.44 no.3
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• pp.324-330
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• 2015

In this study, the anti-diabetic activity of a cold water extract of Korean mistletoe (KME) was investigated in C57BL/6J Lep ob (ob/ob) mice. Oral administration of KME (50 or 100 mg/kg/d) significantly inhibited the level of blood glucose of ob/ob mice after 5 days from the beginning of KME treatment. And the anti-diabetic effect of KME was stabilized 10 days after oral administration, showing a substantial reduction of blood glucose levels by more than 20% as compared with control mice. The results of oral glucose tolerance test (OGTT) revealed that oral administration of KME gave rise to a remarkable improvement in overall glucose response. Oral administration of KME in ob/ob diabetic mice also significantly reduced blood total cholesterol (TCHO) and triglyceride (TG) levels compared with the diabetic control mice. Moreover, in an in vitro experiment using C2C12 myotubes, treatment of KME prominently increased glucose uptake. Interestingly, KME significantly increased the expression of peroxisome proliferator-activated receptor gamma coactivator 1-${\alpha}$ ($PGC-1{\alpha}$), a head regulator of mitochondrial biogenesis and oxidative metabolism, and $PGC-1{\alpha}$-associated genes such as glucose transporter type 4 (GLUT4), estrogen-related receptor-${\alpha}$ ($ERR-{\alpha}$), nuclear respiratory factor-1 (NRF-1), and mitochondrial transcription factor A (TmfA) in C2C12 cells. These results suggest that KME has potential as a novel therapeutic agent for diabetes, and its anti-diabetic activity may be related to the regulation of mitochondrial biogenesis.

• Journal of the Korean Society of Food Science and Nutrition
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• v.43 no.10
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• pp.1477-1483
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• 2014

This study investigated the anti-obesity effects of African mango (Irvingia gabonesis, IGOB $131^{TM}$) extract in leptin-deficient obese mice. Experimental groups were treated with two different doses of IGOB $131^{TM}$ (1% and 2% in each AIN93G supplement) for 8 weeks. Treatment of obese mice with both low and high dose of IGOB $131^{TM}$ significantly reduced body weight gain by 10.9% and 13.3%, respectively, compared to control obese mice. Subcutaneous adipose tissue weight of mice was significantly reduced by 18% by low-dose and 23% by high-dose supplementation. This result was supported by micro-CT analysis around the abdominal regions of mice, indicating that the adipose tissue area and volume were significantly reduced by treatment with IGOB $131^{TM}$. Serum levels of triglycerides in the low- and high-dose groups were reduced by 36.5% and 43.8%, respectively, upon treatment with IGOB $131^{TM}$, whereas total cholesterol levels were reduced by 31.8% and 35.4%. Interestingly, the serum LDL level decreased upon treatment with IGOB $131^{TM}$ while the serum level of HDL dramatically increased upon high-dose treatment with IGOB $131^{TM}$, resulting in a significant reduction in the LDL to HDL ratio of 59.2%. These results were supported by the expression levels of enzymes and proteins related to lipid metabolism assessed by real-time PCR. There was a significant increase of in adiponectin expression as well as significant decreases in the expression of FAS, LPL, and lipid regulatory transcription factors such as PPAR-${\gamma}$, C/EBP, and SREBP upon both low- and high-dose IGOB $131^{TM}$ treatment. However, there was no statistical difference between low- and high-dose treatments. These results suggest that IGOB $131^{TM}$ is able to regulate the serum lipid profiles by reducing triglyceride and increasing HDL levels as well as regulate expression of lipid metabolic factors, resulting in reduction of a weight gain in leptin-deficient obese mice.

• Journal of Life Science
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• v.28 no.4
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• pp.435-443
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• 2018

AMP-activated protein kinase (AMPK) functions as a metabolic master through regulating and restoring cellular energy balance. In skeletal muscle, AMPK increases myofibril protein degradation through the expression of muscle-specific ubiquitin ligases. Mori Folium, the leaf of Morus alba, is a traditional medicinal herb with various pharmacological functions; however, the effects associated with muscle atrophy have not been fully identified. In this study, we confirmed the effects of AMPK activation by examining the effects of 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), an activator of AMPK, on the induction of atrophy and expression of atrophy-related genes in C2C12 myotubes. We also investigated the effects of the ethanol extract of Mori Folium (EEMF) on the recovery of AICAR-induced muscle atrophy in C2C12 myotubes. It was found that exposure to AICAR resulted in the stimulation of Forkhead box O3a (FOXO3a); an up-regulation of muscle-specific ubiquitin ligases such as Muscle Atrophy F-box (MAFbx)/atrogin-1 and muscle RING finger-1 (MuRF1), and a down-regulation of muscle-specific transcription factors, such as MyoD and myogenin; with the activation of AMPK. In addition, AICAR without cytotoxicity indicated a decrease in diameter of C2C12 myotubes. However, treatment with EEMF significantly suppressed AICAR-induced muscle atrophy of C2C12 myotubes in a dose-dependent manner as confirmed by a decrease in myotube diameter, which is associated with a reversed stimulation of FOXO3a by the inhibition of AMPK activation. These results indicate that the activation of AMPK by AICAR induces muscle atrophy, and EEMF has preeminent effects on the inhibition of AICAR-induced muscle atrophy through the AMPK signaling pathway.

• Korean Journal of Organic Agriculture
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• v.15 no.2
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• pp.195-205
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• 2007

This study was conducted to determine effects of probiotics on performance, nutrient digestibility and nitrogen retention in Korean black goats fed two diets differing in forage to concentrate (F:C) ratio (30:70 and 70:30), for the establishment of their more efficient feeding management system. The probiotics employed in this trial were mixtures of different microbial species, which consisted of Lactobacillus casei, Bacillus subtilis, Saccharomyces cerevisiae, Aspergillus oryzae and Streptomyces griseus. Additional levels of probiotics to each F:C ratio (70:30 or 30:70) were 0 and 0.2%, respectively. Thus, twelve Korean black male goats were allotted to treatments in four groups of three goats per treatment and then they were housed in individual metabolism cages with a randomized complete block design for 21 days. Dry matter (DM) intakes were not affected by dietary F:C ratio and probiotics. Digestible DM amounts were significantly (p<0.05) decreased with increasing levels of dietary forage, but they were not affected by probiotics addition. Dry matter intakes per metabolic body weight and their ratio per body weight had a similar trend to DM intakes with no significant difference by F:C ratio and probiotics addition. The nutrient digestibility was significantly (p<0.05) increased with decreasing levels of forage in the diet, but it was not affected by probiotics addition. Urinary nitrogen loss was significantly (p<0.05) decreased with decreasing levels of dietary forage, but there was no significant difference between probiotics-supplemented and unsupplemented groups within the same F:C ratio. On the contrary, nitrogen retention was decreased with increasing levels of dietary forage, and probiotics supplementation to two diets differing in F:C ratio showed slightly increasing trends in the nitrogen retention. From the above results, probiotics supplementation to two diets differing in F:C ratio did not have the significant influence on feed intakes, nutrient digestibility and nitrogen retention. Consequently, these parameters of Korean black goats were dominated rather by F:C ratio than by dietary probiotics.

• Asian-Australasian Journal of Animal Sciences
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• v.13 no.12
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• pp.1681-1690
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• 2000

A study on energy and protein utilization, and milk production of Bali cows on grass-legume diets was carried out using 12 first lactation cows (initial BW $263.79{\pm}21.66kg$) during a period of 16 weeks starting immediately post calving. The animals were randomly allotted into 4 dietary treatment groups R1, R2, R3 and R4, receiving from the last 2 months of pregnancy onwards, graded improved rations based on a mixture of locally available grass and legume feed ad libitum. R1 contained on a DM basis 70% elephant grass (PP, Penisetum purpureum) plus 30% Gliricidia sepia leaves (GS), R2 was 30% PP plus 55% GS supplemented with 15% Hibiscus tilliactus leaves (HT, defaunating effect), R3 and R4 were 22.5% PP+41.25% GS+11.25% HT+25% concentrate, where R3 was not and R4 supplemented with zinc di-acetate. TDN, CP and zinc contents of the diets were 58.2%, 12.05% and 18.3 mg/kg respectively for R1, 65.05%, 16.9% and 25.6 mg/kg respectively for R2, 66.03%, 16.71% and 29.02 mg/kg respectively for R3 and 66.03%, 16.71% and 60.47 mg/kg respectively for R4. Milk production and body weight were monitored throughout the experimental period. In vivo body composition by the urea space technique validated by the body density method and supported by carcass data was estimated at the start and termination of the experiment. Nutrient balance and rumen performance characteristics were measured during a balance trial of 7 days during the 3rd and 4th week of the lactation period. Results indicated that quality of ration caused improvement of ruminal total VFA concentration, increments being 52 to 65% for R2, R3 and R4 above R1, with increments of acetate being less (31 to 48%) and propionate being proportionally more in comparison to total VFA increments. Similarly, ammonia concentrations increased to 5.24 to 7.07 mM, equivalent to 7.34 to 9.90 mg $NH_3-N/100ml$ rumen fluid. Results also indicated that feed quality did not affect DE and ME intakes, and heat production (HP), but increased GE, UE, energy in milk and total retained energy (RE total) in body tissues and milk. Intake-, digestible- and catabolized-protein, and retained-protein in body tissues and milk (Rprot) were all elevated increasing the quality of ration. Similar results were obtained for milk yield and components with mean values reaching 2.085 kg/d (R4) versus 0.92 kg/d (R1) for milk yield, and 170.22 g/d (R4) vs 71.69 g/d (R1), 105.74 g/d (R4) vs 45.35 g/d (R1), 101.34 g/d (R4) vs 46.36 g/d (R1) for milk-fat, -protein, and -lactose, respectively. Relatively high yields of milk production was maintained longer for R4 as compared to the other treatment groups. There were no significant effects on body mass and components due to lactation. From the relationship $RE_{total}$ (MJ/d)=12.79-0.373 ME (MJ/d); (r=0.73), it was found that $ME_{m}=0.53MJ/kgW^{0.75}.d$. Requirement of energy to support the production of milk, ranging from 0.5 to 3.0 kg/d, follows the equation: Milk Prod. ($Q_{mp}$, kg/d)=[-2.48+4.31 ME($MJ/kg^{0.75}.d$)]; (r=0.6) or $Q_{mp}$=-3.4+[0.08($ME-RE_{body\;tissue}$)]MJ/d]; (r=0.94). The requirement for protein intake for maintenance ($IP_m$) equals $6.19 g/kg^{0.75}.d$ derived from the relationship RP=-47.4+0.12 IP; (r=0.74, n=9). Equation for protein requirement for lactation is $Q_{nl}$=[($Q_{mp}$)(% protein in milk)($I_{mp}$)]/100, where $Q_{nl}$ is g protein required for lactation, $Q_{mp}$ is daily milk yield, Bali cow's milk-protein content av. 5.04%, and $I_{mp}$ is metabolic increment for milk production ($ME_{lakt}/ME_{m}=1.46$).