• 생명과학회지
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• 제32권10호
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• pp.762-770
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• 2022

제 2형 당뇨병은 고혈당을 특징으로 하는 만성 대사성 질환으로 인슐린 민감성및 저항성을 개선하여 세포속으로 포도당 흡수를 촉진시킴으로서 완화될 수 있다. 본 연구는 triterpenoid 화합물인 betulinic acid가 3T3-L1 지방세포에서 인슐린 신호전달체계를 개선하여 포도당 흡수를 촉진시키는지를 조사하고 그 작용기전을 규명하였다. Betulinic acid는 3T3-L1 지방세포에서 농도의존적으로 포도당 흡수를 유의하게 증가시켰으며, 이는 PM-GLUT4의 발현 증가와 관련이 있음을 관찰하였다. Betulinic acid는 인슐린 신호전달 경로에서 PI3K의 활성화 및 IRS-1tyr, Akt의 인산화를 대조군에 비해 유의하게 증가시켰다. 또한 AMPK의 활성화를 나타내는 pAMPK와 AMPK 하위인자인 pACC의 수준을 유의하게 증가시켰다. Betulinic acid에 의한 PI3K 및 AMPK 경로의 활성화를 증명하기 위해, PI3K 억제제(Wortmannin)와 AMPK의 억제제(Compound C)를 사용하여 이들 처리에 의한 포도당 흡수능과 PM-GLUT4의 발현을 측정한 결과 이들의 발현이 유의하게 저해되었다. 본 연구에서 betulinic acid는 3T3-L1 지방세포에서 PI3K 및 AMPK 경로의 활성화를 통해 세포막으로 포도당 수송체인 GLUT4 전위를 촉진시키고 포도당 흡수를 증가시킬 수 있음을 나타내었다. 이러한 결과는 betulinic acid가 인슐린 민감성을 증진시키고 고혈당을 완화하는데 도움이 될 수 있음을 시사한다.

• Asian-Australasian Journal of Animal Sciences
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• 제30권2호
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• pp.236-245
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• 2017

Objective: The study was to investigate the effects of alanyl-glutamine (Ala-Gln) and glutamine (Gln) supplementation on the intestinal mucosa barrier in piglets. Methods: A total of 180 barrows with initial weight $10.01{\pm}0.03kg$ were randomly allocated to three treatments, and each treatment consisted of three pens and twenty pigs per pen. The piglets of three groups were fed with control diet [0.62% alanine (Ala)], Ala-Gln diet (0.5% Ala-Gln), Gln diet (0.34% Gln and 0.21% Ala), respectively. Results: The results showed that in comparison with control diet, dietary Ala-Gln supplementation increased the height of villi in duodenum and jejunum (p<0.05), Gln supplementation increased the villi height of jejunum (p<0.05), Ala-Gln supplementation up-regulated the mRNA expressions of epidermal growth factor receptor and insulin-like growth factor 1 receptor in jejunal mucosa (p<0.05), raised the mRNA expressions of Claudin-1, Occludin, zonula occludens protein-1 (ZO-1) and the protein levels of Occludin, ZO-1 in jejunal mucosa (p<0.05), Ala-Gln supplementation enlarged the number of goblet cells in duodenal and ileal epithelium (p<0.05), Gln increased the number of goblet cells in duodenal epithelium (p<0.05) and Ala-Gln supplementation improved the concentrations of secretory immunoglobulin A and immunoglobulin G in the jejunal mucosa (p<0.05). Conclusion: These results demonstrated that dietary Ala-Gln supplementation could maintain the integrity of small intestine and promote the functions of intestinal mucosa barriers in piglets.

• Asian-Australasian Journal of Animal Sciences
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• 제20권10호
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• pp.1606-1611
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• 2007

The experiment was conducted to investigate the effects of dihydropyridine on laying performance and fat metabolism of laying hens. Five hundred and forty laying hens, 40 weeks old, were randomly allotted to three groups, each of which included four replicates of 45 hens. The groups were given a basal corn-soybean meal diet supplemented with 0, 150 mg/kg and 300 mg/kg dihydropyridine. Results showed that compared with the control group (0 mg/kg dihydropyridine), supplements of 150 and 300 mg/kg dihydropyridine increased egg production rate by 9.39% (p<0.01) and 12.97% (p<0.01), increased mean egg weight by 3% (p>0.05) and 4.8% (p>0.05), and improved feed efficiency by 9.54% (p<0.05) and 7.25% (p<0.05), respectively; The addition of 150 and 300 mg/kg dihydropyridine decreased percentage of abdominal fat by 35.4% (p<0.05) and 46.9% (p<0.05), decreased liver fat content by 32.4% (p<0.05) and 10.5% (p<0.05), increased HSL activity of abdominal fat by 39.64% (p<0.05) and 48.48% (p<0.05), increased HSL activity of liver by 9.4% (p>0.05) and 47.34% (p<0.05) and increased the content of cAMP in adenohypophysis by 14.67% (p<0.05) and 10.91% (p<0.05), respectively; The inclusion of 150 mg/kg dihydropyridine increased liver superoxide dismutase activity by 69.61% (p<0.05), and increased hepatic apoB concentration by 53.96% (p<0.05); The supplementation of 150 or 300 mg/kg dihydropyridine decreased malondialdehyde concentration of hepatic mitochondria by 30.90% (p<0.01) and 10.39% (p<0.05), respectively; Supplemented dihydropyridine had no significant effects on TG, Ch HDL-C and VLDL-C concentrations in serum; addition of 150 or 300 mg/kg dihydropyridine increased T3 levels in serum by 15.34% (p<0.05) and 11.88% (p<0.05) and decreased insulin concentration by 40.44% (p<0.05) and 54.37% (p<0.05), respectively. The results demonstrated that adding dihydropyridine had the tendency of improving very low density lipoprotein receptor (VLDLR) content in the ovary. It was concluded that dihydropyridine could improve laying performance and regulate the fat metabolism of laying hens and that 150 mg/kg dihydropyridine is the optimum dose for laying birds in practical conditions.

• Asian-Australasian Journal of Animal Sciences
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• 제22권8호
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• pp.1069-1077
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• 2009

Castration of male pig produces significant negative effects on skeletal muscle development. The androgen receptor (AR), two splice variants of insulin-like growth factor-I (IGF-I Ea and MGF) and the myostatin gene may play important roles in this process. In the present study, the expression of AR, IGF-I Ea, MGF and myostatin genes in three skeletal muscles, the brachialis, longissimus and semitendinosus, were studied using real-time quantitative RT-PCR. Our experimental design used 14 pairs of male Landrace sire${\times}$Yorkshire dam piglets. The two piglets in each pair were full sibs, one of which was castrated at 21 d of age; the other remained intact. The study group was divided into subgroups of equal size. Animals in the first subgroup were slaughtered at 147 d and those of the second at 210 d of age. Carcass weight and lean meat yield were similar between boars and barrows at 147 d of age (p>0.05), whereas barrows had lower carcass weight and less lean meat yield at 210 d of age (p<0.05). Castration caused down-regulation of AR gene expression at both 147 and 210 d of age (p<0.05). The two splice variants of the IGF-I gene from porcine skeletal muscle were cloned using RT-PCR, and it was found that MGF differs from IGF-I Ea in having a 52-base insert in the last coding exon of the mRNA. Both splice variants were down-regulated by castration only at 210 d of age (p<0.05). No differences in expression of the myostatin gene were observed between boars and barrows at either 147 or 210 d of age (p>0.05). These results suggest that the downregulation of AR, IGF-I Ea and MGF gene expression following castration helps to explain the negative effect of castration on skeletal muscle development.

• 생명과학회지
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• 제19권9호
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• pp.1200-1208
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• 2009

Tight junctions (TJs)은 인접된 세포 사이의 전해질 및 거대분자 확산 조절에 관여하는 paracellular permeability의 장벽 역할을 한다. 본 연구에서는 MCF-7 및 MDA-MB-231 인체유방암세포에서 대두의 대표적인 생리활성물인 genistein에 의한 암세포의 침윤 억제에서 TJs의 견고성 및 투과성과의 연관성을 조사하였다. 본 연구의 결과에 의하면 genistein에 의한 유방암세포의 증식 억제, 암세포 이동성의 저하 및 침윤성의 억제는 TJs의 증가된 견고성과 연관이 있었으며, 이를 transepithelial electrical resistance의 증가 및 paracellular permeability의 감소로 확인하였다. Genistein은 두 유방암세포에서 TJs의 주요 조절 단백질로서 paracellular transport 조절에 중요한 역할을 하는 claudin-3 및 claudin-4의 발현을 억제시켰다. 그리고 genistein은 암세포의 전이 조절 관련 유전자들인 like growth factor-1 receptor 및 snail의 발현을 억제하였으며, thrombospondin-1 및 E-cadherin의 발현은 증가시켰다. 또한 small interfering RNA를 이용하여 genistein의 유방암세포의 침윤 억제에서 claudin-3단백질의 중요성을 확인하였다. 결론적으로 genistein이 TJs의 견고성 증가를 통하여 암세포의 침윤성을 억제할 수 있었으며, 이 과정에서 아마도 claudin 단백질의 발현 증가가 중요한 역할을 하고 있음을 알 수 있었다. 본 연구의 결과는 genistein이 종양 전이억제를 효과적으로 차단할 수 있음을 보여주는 것이다.

• Molecular & Cellular Toxicology
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• 제5권3호
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• pp.193-197
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• 2009

Suppressors of cytokine signaling (SOCS) proteins were originally identified as negative feedback regulators of cytokine signaling and include the Janus kinase/Signal transducer and activator of transcription (JAK/STAT) pathways. Recent studies have shown that SOCS proteins negatively regulate the receptor tyrosine kinase (RTK) pathway including the insulin receptor (IR), EGFR, and KIT signaling pathways. In addition, SOCS1 and SOCS3 have been reported to have anti-tumor effects in human hepatocellular carcinoma (HCC). However, it is uncertain whether other members of the SOCS family are associated with tumor development and progression. In this study, to investigate whether SOCS6 is aberrantly regulated in HCC, we examined the expression level of SOCS6 in HCC by Western blot analysis and immunohistochemical staining. The results showed that SOCS6 was down-regulated in all examined HCCs compared to the corresponding normal tissues. In addition, expression of SOCS6 was observed in the cytoplasm of most normal and precancerous tissue, but not in the HCCs by immunohistochemical staining. This is first report to demonstrate that SOCS6 is aberrantly regulated in HCC. These findings suggest that underexpression of SOCS6 is involved in hepatocarcinogenesis, and SOCS6 may play a role, as a tumor suppressor, in HCC development and progression.

• Journal of Nutrition and Health
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• 제40권3호
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• pp.221-228
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• 2007

We determined the effects of dietary manipulations on messenger RNA of peroxisome proliferators activated receptor isoforms (i.e., PPAR ${\alpha},\;{\beta}/{\delta},\;{\gamma}$) in red vastus lateralis muscle of rats. Total 16 male Sprague-Dawley rats were used, and animals were divided into one of two dietary conditions: either chow diet group (CHOW; n=8) in which animals were 134 with standard rodent chow (61.8% carbohydrate, 15.7% fat, 22.5% protein) or high fat diet group (FAT n=8) in which animals were fed 24.3% carbohydrate, 52.8% fat, 22.9% protein. At the end of the 8 weeks of experimental period, red vastus lateralis muscle was dissected out from all animals, and PPAR ${\alpha},\;{\beta}/{\delta},\;{\gamma}$ mRNA expression was determined. There was no significant difference in body mass (BM) between CHOW and FAT. As expected, blood glucose and free fatty acid (FFA) concentration was higher in FAT than CHOW (p<0.05), and lactate concentration was significantly lower in FAT compared to CHOW (p<0.05). Insulin concentration tended to higher in FAT than CHOW ($67.2{\pm}21.9\;vs.\;27.0{\pm}5.2$ pmol/L), but it did not reach to the statistical significance. Gene expression of PPAR ${\alpha}$ was not significantly different between CHOW and FAT. It was not also significantly different in PPAR ${\beta}/{\delta}$. Interestingly, expression of mRNA in PPAR ${\gamma}$ however, was markedly depressed in FAT compared to CHOW (approximately 3 fold higher in CHOW; p<0.05). Results obtained from present study implies that PPAR ${\gamma}$ (as compensatory function of PPAR ${\alpha}$ is expressed) possibly exerts another major tuning roles in fatty acid transport, utilization, as well as biosynthesis in skeletal muscle cells. The situations and conditions that can be postulated for this implication need to be further examined.

• Asian-Australasian Journal of Animal Sciences
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• 제31권8호
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• pp.1088-1097
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• 2018

Objective: It is commonly accepted that adiponectin binds to its two receptors to regulate fatty acid metabolism in adipocytes. To better understand their functions in the regulation of intramuscular adipogenesis in goats, we cloned the three genes (adiponectin [AdipoQ], adiponectin receptor 1 [AdipoR1], and AdipoR2) encoding these proteins and detected their mRNA distribution in different tissues. We also determined the role of AdipoQ in the adipogenic differentiation of goat skeletal muscle satellite cells (SMSCs). Methods: SMSCs were isolated using 1 mg/mL Pronase E from the longissimus dorsi muscles of 3-day-old female Nanjiang brown goats. Adipogenic differentiation was induced in satellite cells by transferring the cells to Dulbecco's modified Eagle's medium supplemented with an isobutylmethylxanthine, dexamethasone and insulin cocktail. The pEGFP-N1-AD plasmid was transfected into SMSCs using Lipofectamine 2000. Expression of adiponectin in tissues and SMSCs was detected by quantitative polymerase chain reaction and immunocytochemical staining. Results: The three genes were predominantly expressed in adipose and skeletal muscle tissues. According to fluorescence and immunocytochemical analyses, adiponectin protein expression was only observed in the cytoplasm, suggesting that adiponectin is localized to the cytoplasm of goat SMSCs. In SMSCs overexpressing the AdipoQ gene, adiponectin promoted SMSC differentiation into adipocytes and significantly (p<0.05) up-regulated expression of AdipoR2, acetyl-CoA carboxylase, fatty-acid synthase, and sterol regulatory element-binding protein-1, though expression of CCAAT/enhancer-binding $protein-{\alpha}$, peroxisome proliferator-activated receptor ${\gamma}$, and AdipoR1 did not change significantly. Conclusion: Adiponectin induced SMSC differentiation into adipocytes, indicating that adiponectin may promote intramuscular adipogenesis in goat SMSC.

• 생명과학회지
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• 제31권9호
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• pp.796-805
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• 2021

간 소포체(ER) 스트레스는 비알콜성지방간과 인슐린 저항성의 발달에 기여하고, unfolded protein response(UPR)의 구성요소는 지질 대사를 조절한다. 최근 연구에 따르면 ER 스트레스와 비정상적인 세포 지질 대사 사이의 연관성이 보고되었으며, 이 과정에서 지질 대사의 중심 조절자인 sterol regulatory element binding proteins(SREBPs)의 관련성이 확인되었다. 그러나 ER 스트레스 동안 지질 대사를 조절하는 SREBP의 정확한 역할과 비알콜성지방간에 대한 기여는 아직 밝혀지지 않았다. 본 연구에서 SREBP-1c 결핍은 UPR, 염증 및 지방산 산화 조절을 통해 ER 스트레스에 의해 유도된 비알콜성지방간으로부터 생쥐를 보호한다는 것을 보여준다. SREBP-1c는 inositol requiring kinase 1α (IRE1α) 발현을 직접적으로 조절하고 ER 스트레스에 의해 유도된 tumor necrosis factor-α의 활성화를 매개하여 peroxisome proliferator-activated receptor γ coactivator 1-α (PGC1α)의 감소와 그에 따른 지방산 산화의 장애를 유발한다. 그러나, SREBP-1c의 유전적 결핍은 이러한 현상을 보호하여 간 염증과 지방 축적을 완화시킨다. SREBP-1c 결핍이 ER 스트레스에 의해 유도된 염증 신호를 방지하는 메커니즘은 아직 밝혀지지 않았지만, SREBP-1c가 결핍된 Kupffer 세포에서 IRE1α 신호의 변화가 염증 신호에 관여할 수 있을 것으로 생각된다. 본 연구결과는 SREBP-1c가 ER 스트레스에 의해 유도된 비알콜성지방간에서 UPR 및 염증의 조절에 중요한 역할을 함을 시사한다.

• Animal Bioscience
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• 제35권7호
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• pp.989-998
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• 2022

Objective: This study investigated the effects of intrauterine growth restriction (IUGR) during late pregnancy on the cell growth, proliferation, and differentiation in ovine fetal thymuses. Methods: Eighteen time-mated Mongolian ewes with singleton fetuses were allocated to three groups at d 90 of pregnancy: restricted group 1 (RG1, 0.18 MJ ME/body weight [BW]^0.75/d, n = 6), restricted group 2 (RG2, 0.33 MJ ME/BW^0.75/d, n = 6) and control group (CG, ad libitum, 0.67 MJ ME/BW^0.75/d, n = 6). Fetuses were recovered at slaughter on d 140. Results: The G0/G1 phase cell number in fetal thymus of the RG1 group was increased but the proliferation index and the expression of proliferating cell nuclear antigen (PCNA) were reduced compared with the CG group (p<0.05). Fetuses in the RG1 group exhibited decreased growth hormone receptor (GHR), insulin-like growth factor 2 receptor (IGF-2R), and their mRNA expressions (p<0.05). For the RG2 fetuses, there were no differences in the proliferation index and PCNA expression (p>0.05), but growth hormone (GH) and the mRNA expression of GHR were lower than those of the CG group (p<0.05). The thymic mRNA expressions of cyclin-dependent protein kinases (CDKs including CDK1, CDK2, and CDK4), CCNE, E2-factors (E2F1, E2F2, and E2F5) were reduced in the RG1 and RG2 groups (p<0.05), and decreased mRNA expressions of E2F4, CCNA, CCNB, and CCND were occurred in the RG1 fetuses (p<0.05). The decreased E-cadherin (E-cad) as a marker for epithelial-mesenchymal transition (EMT) was found in the RG1 and RG2 groups (p<0.05), but the OB-cadherin which is a marker for activated fibroblasts was increased in fetal thymus of the RG1 group (p<0.05). Conclusion: These results indicate that weakened GH/IGF signaling system repressed the cell cycle progression in G0/G1 phase in IUGR fetal thymus, but the switch from reduced E-cad to increased OB-cadherin suggests that transdifferentiation process of EMT associated with fibrogenesis was strengthened. The impaired cell growth, retarded proliferation and modified differentiation were responsible for impaired maturation of IUGR fetal thymus.