• Nutrition Research and Practice
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• 제10권4호
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• pp.386-392
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• 2016

BACKGROUND/OBJECTIVES: Changes in nutritional status during gestation and lactation have detrimental effects on offspring metabolism. Several animal studies have shown that maternal high-fat diet (HFD) can predispose the offspring to development of obesity and metabolic diseases, however the mechanisms underlying these transgenerational effects are poorly understood. Therefore, we examined the effect of maternal HFD consumption on metabolic phenotype and hepatic expression of involved genes in dams to determine whether any of these parameters were associated with the metabolic outcomes in the offspring. MATERIALS/METHODS: Female C57BL/6 mice were fed a low-fat diet (LFD: 10% calories from fat) or a high-fat diet (HFD: 45% calories from fat) for three weeks before mating, and during pregnancy and lactation. Dams and their male offspring were studied at weaning. RESULTS: Dams fed an HFD had significantly higher body and adipose tissue weights and higher serum triglyceride and cholesterol levels than dams fed an LFD. Hepatic lipid levels and mRNA levels of genes involved in lipid metabolism, including $LXR{\alpha}$, SREBP-2, FXR, LDLR, and ABCG8 were significantly changed by maternal HFD intake. Significantly lower total liver DNA and protein contents were observed in dams fed an HFD, implicating the disturbed liver adaptation in the pregnancy-related metabolic demand. HFD feeding also induced significant oxidative stress in serum and liver of dams. Offspring of dams fed an HFD had significantly higher serum cholesterol levels, which were negatively correlated with liver weights of dams and positively correlated with hepatic lipid peroxide levels in dams. CONCLUSIONS: Maternal HFD consumption induced metabolic dysfunction, including altered liver growth and oxidative stress in dams, which may contribute to the disturbed cholesterol homeostasis in the early life of male mice offspring.

• Genomics & Informatics
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• 제10권4호
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• pp.256-262
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• 2012

Most common complex traits, such as obesity, hypertension, diabetes, and cancers, are known to be associated with multiple genes, environmental factors, and their epistasis. Recently, the development of advanced genotyping technologies has allowed us to perform genome-wide association studies (GWASs). For detecting the effects of multiple genes on complex traits, many approaches have been proposed for GWASs. Multifactor dimensionality reduction (MDR) is one of the powerful and efficient methods for detecting high-order gene-gene ($G{\times}G$) interactions. However, the biological interpretation of $G{\times}G$ interactions identified by MDR analysis is not easy. In order to aid the interpretation of MDR results, we propose a network graph analysis to elucidate the meaning of identified $G{\times}G$ interactions. The proposed network graph analysis consists of three steps. The first step is for performing $G{\times}G$ interaction analysis using MDR analysis. The second step is to draw the network graph using the MDR result. The third step is to provide biological evidence of the identified $G{\times}G$ interaction using external biological databases. The proposed method was applied to Korean Association Resource (KARE) data, containing 8838 individuals with 327,632 single-nucleotide polymorphisms, in order to perform $G{\times}G$ interaction analysis of body mass index (BMI). Our network graph analysis successfully showed that many identified $G{\times}G$ interactions have known biological evidence related to BMI. We expect that our network graph analysis will be helpful to interpret the biological meaning of $G{\times}G$ interactions.

• Journal of Nutrition and Health
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• 제43권4호
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• pp.357-366
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• 2010

There has been no genome-wide association study (GWAS) for macronutrient intake as a quantitative trait. To explore genetic loci associated with total calorie and macronutrient intake, genome-wide association data of autosomal single nucleotide polymorphisms (SNPs) from Korean adults were analyzed. We conducted a GWAS in 3,690 men and women aged 40 to 60 years from an urban population-based cohort. At the baseline examination (June 18, 2001 through January 29, 2003), DNA samples of the study subjects were collected and analyzed for genotyping. The information of average daily consumption of total calorie, carbohydrate, protein, and fat was obtained from a semi-quantitative food frequency questionnaire and transformed by natural logarithm for analyses after adjustment of calorie intake. Using multivariate linear regression analysis adjusted for age, sex, and height, we tested for 352,021 SNPs and found weak associations, which do not reach genome-wide association significance, with calorie and macronutrient intake. However, a number of SNPs were found to have potential associations with macronutrient intake; in particular, signals in SORBS1 and those in PRKCB1 were likely associated with carbohydrate and fat intake, respectively. We observed an inverse association between the minor allele of the SNPs in these genes and the amount of consumption of carbohydrate or fat. Our GWAS identified loci and minor alleles weakly associated with macronutrient intake. Because SORBS1 and PRKCB1 are reportedly associated with the metabolism of glucose and lipid as well as with obesity-related diseases, further investigations on biological and functional roles of polymorphism of these genes in the relation to macronutrient intake are warranted.

• Journal of Nutrition and Health
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• 제47권1호
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• pp.1-11
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• 2014

널리 음용되고 있는 녹차의 EGCG과 우리나라 국민의 상당수가 복용하고 있는 건강기능성 식품 성분인 글루코사민은 이전의 연구들을 통해서 지방세포의 분화를 억제하는데 효과가 있다고 보고되어왔다. 이 두 물질의 병합처리로 기대되어지는 지방세포에서의 adipogenesis 및 지방축적감소에 대한 상승효과는 검증된 바 없으며, 효과에 대한 cell cycle 차원에서의 접근은 없었다. 본 연구 결과에서 EGCG와 Glucosamine 6-phosphate는 adipogenesis 전사인자인 $PPAR{\gamma}$, $C/EBP{\alpha}$, SREBP1에 대한 직접적인 발현 억제 뿐아니라, $PPAR{\gamma}$, $C/EBP{\alpha}$, SREBP1와 매개된 FAS, ACSL1, LPL과 같은 adipogenic target 유전자의 발현 감소를 통하여 지방세포의 분화와 지방세포 내 지방축적을 감소시키는 효과를 나타냈다. 그리고 HSL과 perilipin의 발현조절을 통해 부분적인 lipolytic effet도 나타냈다. 또한 지방세포의 분화가 개시되는데 있어 중요한 DNA의 remodeling 과정인 mitotic clonal expansion (MCE) 과정 중 G0/G1 phase 단계에서 cell cycle 정지 유도와 그로인한 S phase 및 G2/M phase로 세포주기이행의 방해를 통해 지방세포가 분화되는 것은 억제하였다. 이러한 효과들은 EGCG 농도가 높아질수록, 그리고 EGCG를 단독으로 처리한경우보다 Glucosamine 6-phosphate와 병합하였을 때 효과적이었다. 따라서 EGCG 단독처리 및 glucosamine 6-phosphate와의 병합처리는 지방세포에서 adipogenesis와 adipogenic관련 유전자들의 발현 억제 및 MCE 단계의 cell cycle arrest를 통해 지방세포의 분화를 억제하고 지방축적을 감소시켜 항비만 효과를 나타냈으며, 이러한 효과는 두 성분의 병합처리에서 조금 더 효과적이었다고 할 수 있다. 비록 두 성분의 병합처리가 기대했던 만큼은 아니었으나 항비만 효과에 대한 상승효과가 있다고 볼 수 있다.

• Journal of Nutrition and Health
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• 제54권5호
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• pp.448-458
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• 2021

본 연구는 뽕나무 열매 착즙 분말 (MJ)이 지방세포 분화과정에서 염증에 관여하는 유전자 발현 및 miR-132/143 조절에 미치는 효과에 중점을 두고 조사하였다. MJ는 3T3-L1 지방세포 분화 동안 지질축적이 억제되었고 PPAR-γ, CEBP-α 및 aP2와 같은 지방형성 유전자 발현을 억제하였다. 또한 염증 조절 매개체인 TNF-α, IL-6, MCP-1 및 iNOS 유전자 발현이 MJ 처리에 의해 감소되었다. MJ의 지질 축적 억제 효과는 염증과 지방분화에 관여하는 miR-132/143의 발현 감소와 관련이 있음을 확인하였다. 따라서 MJ는 염증을 동반하는 비만 예방 및 치료에 도움이 될 수 있는 식품 소재로서 가능성이 있음을 시사하고 있다. 그러나 MJ의 주요 성분인 안토시아닌의 생체이용율은 1-2% 미만으로 추정되며 예상되는 표적 조직이나 혈류에서 미량 검출되는 것으로 알려져 있다 [33]. 이를 해결하기 위해서는 생체 내 동물실험을 통한 다각적인 분석이 향후 진행되어야 할 것으로 판단된다.

• 동의생리병리학회지
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• 제24권3호
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• pp.504-511
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• 2010

Diabetes is a disease that contains a high concentration of glucose in blood and due to defects in either insulin secretion or insulin action. Although the distinctive causes and factors of diabetes have not been clarified, the genetic factors are suggested as a main susceptibility until now. SNP (Single Nucleotide Polymorphism), as the most common genetic variation, has an influence on personal susceptibility for diseases. A nonsynonymous SNP, which changes the amino acid of the protein and its function, is especially important. Therefore, this study hypothesized that there are associations between specific SNPs of the targeted genes. Transcription factor 7-like 2 (TCF7L2) and fat mass and obesity associated (FTO) genes were selected as target genes from the results of genome-wide association and other related research studies. Second, four nonsynonymous SNPs (three in TCF7L2 and one in FTO gene) were selected as target SNPs by using public database of NCBI (National Center for Biotechnology Information). The recruited personnel was classified into three subgroups of diabetes, impaired fasting glucose (IFG) and normal groups. The individual genotypes of each group were analyzed by resequencing. None of genetic variations at four targeted SNP sites was revealed in all samples of this study. However, this study found two new SNPs that were not reported in TCF7L2 gene. One is synonymous SNP, which is heterozygous of C/T and no amino acid change of asparagine/asparagines, was located at c1641 and found in one normal person. Another is nonsynonymous SNP, which is heterozygous of G/A, was located at c1501 and found in two samples. This new discovered nonsynonymous SNP induce the amino acid change from alanine to threonine. Moreover, this new nonsynonymous SNP was found among two persons, one of whom was a diabetes patient and the other one was a person at boundary between IFG and normal, suggesting that this variant might be associated with IFG or diabetes. Even if there is a limitation of sample number for statistical power, this study has an importance due to the discovery of new SNPs. In the future study, a large sample number of diabetes cohort will be needed to investigate the frequency and association with new discovered SNP.

• Journal of Applied Biological Chemistry
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• 제52권3호
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• pp.103-108
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• 2009

비만은 유방암을 일으키는 잠재적 위험 요소 중 하나이며 현재 이들의 상관관계를 밝히려는 많은 연구들이 진행 중에 있다. 지방세포는 유방조직을 이루는 기질세포 중 가장 높은 비중을 차지하며, 이들이 분비하는 물질인 아디포카인이 유방암의 성장과 전이에 영향을 줄 것으로 예상되어지고 있다. 지방조직이 생산하는 아디포카인들 중 렙틴은 유방암 세포의 증식능력을 증가시키고 아디포넥틴의 경우 반대로 증식억제 기능을 보인다는 연구 결과가 있다. 또한 정상의 경우와 비교해서 비만 환자에게서 렙틴의 양은 증가되어져 있으며 그와 반대로 아디포넥틴은 비만환자에게서 감소 경향을 보인다. 이는 비만에 의하여 변화되는 아디포카인들이 서로 작용하여 비만한 유방암환자의 유방암세포증식을 촉진할 수 있음을 뜻한다. 본 연구에서는 지방세포의 분비 물질인 아디포카인들에 의해 조절되는 유방암세포의 유전자들을 조사하기 위해 유방암세포주인 MDA-MB-231 세포주에 지방세포 배양액을 처리하였으며, 이 증가되는 유전자 중 glucocorticoid-induced TNF receptor-related protein ligand(GITRL)를 선택 연구하였다. GITRL은 지방세포 배양액을 처리한 MDA-MB-231 세포주에서 높게 발현되었으며, proteinase-K를 처리한 지방세포 배양액에 의해서는 발현 정도에 변화가 없었다. 이는 지방세포가 분비하는 단백질인자 중 하나가 유방암 세포의 GITRL 발현을 증가시킴을 말한다. 또한 유방암 세포주 MDA-MB-231 세포에서 증가된 GITRL은 그 자체의 전이 능력에는 영향을 주지 못하였으나, glucocorticoid-induced TNF receptor-related protein(GITR)을 발현하는 자연살해 세포주인 NK92세포와의 상호작용 때에는 전이 능력을 감소시켰다.

• Journal of Nutrition and Health
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• 제50권6호
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• pp.543-551
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• 2017

본 연구는 발효시킨 블루베리액이 고지방식이로 비만이 유도된 C57BL/6J mice에 미치는 항비만 효과 및 기전에 대해 평가하였다. 실험동물은 각 7마리씩 3군으로 나누어 고지방식이와 증류수를 섭취하는 HD군, 고지방식이와 블루베리액을 섭취하는 BHD군, 고지방식이와 블루베리발효액을 섭취하는 FBHD군으로 사육하였다. 경구투여량은 10 mg/kg BW/day로 설정하였고, 이는 12%의 블루베리액(2.5 g 블루베리 함유; 블루베리 함유 안토시아닌 함량은 약 3.75 mg, 총 폴리페놀은 약 10.3 mg 추정)을 나타낸다. 본 연구 결과, 블루베리액과 블루베리발효액은 체중 감소, 체지방량 감소, 간의 중성지방과 총 콜레스테롤 함량을 감소시켰다. 그리고 혈중 LDL-콜레스테롤을 낮추고, HDL-콜레스테롤을 증가시켰으며 AST 및 ALT 농도를 감소시켰다. 또한 렙틴 농도가 낮아졌으며 지방 합성 유전자 발현에서는 SREBP-1c, ACC 발현 수준이 유의적으로 낮아졌으며, 지방 산화 유전자 발현에서는 블루베리발효액의 ACOX 발현 수준이 유의적으로 증가하였다. 결론적으로 BHD군과 FBHD군이 항비만 효과를 나타냈었으며, 특히 FBHD군이 BHD군보다 간에서 총 콜레스테롤 20%, AST 9%, ALT 52%, 지방 합성 유전자 SREBP-1c 발현을 감소시켰고, 혈중 HDL-콜레스테롤 16.4%와 지방 산화 유전자 ACOX 발현을 유의적으로 증가시켰다. 따라서 본 실험의 결과, 블루베리는 고지방 섭취로 인한 콜레스테롤 및 지질변화에 감소 효과를 나타내며, 특히 발효를 통해 기능성이 더욱 증진되는 것으로 나타났다. 발효과정은 블루베리의 항비만 효과를 증진시키며 블루베리발효액은 기능성 식품으로서 이용가치가 높을 것으로 사료된다.

• 한국융합학회논문지
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• 제10권3호
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• pp.127-133
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• 2019

본 연구는 3T3-L1 세포로 하늘타리(Trichosanthes kirilowii Maxim) 뿌리 에탄올 추출물(TKM)의 항비만 활성을 조사하였다. TKM 처리 한 3T3-L1 지방세포의 분화억제를 통한 지방생성 억제에 초점을 두었다. 세포독성을 나타내지 않는 100ug/ml 농도에서 TG 함량을 현저히 억제하고, 세포 초기분화 전사인자 $PPAR{\gamma}$, $C/EBP{\alpha}$, SREBP-1c의 발현 억제, 세포내 에너지 향상성 조절인자 pAMPK, 중성지방산의 합성분해 조절인자 pACC, CPT-1, 지방산 합성 효소(FAS) 발현 억제, 호르몬자극지방분해 효소(HSL) 활성화 등 지방합성 관련인자들의 발현 조절 효능이 있는 것으로 확인되었다. 이상의 결과로 TKM은 지방세포 분화와 지방대사 관련 인자들의 발현을 조절함으로써 지방 생성과 축적 저해 효능을 보여 항비만 융합치료제로의 가능성을 제시하였다.

• Journal of Animal Science and Technology
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• 제62권2호
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• pp.239-246
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• 2020

Microorganism residing in the gut has been known to have important roles in the animal body. Microbes and host microenvironment are highly related with host's health including energy metabolism and immune system. Moreover, it reported that gut microbiome is correlated with diseases like obesity in human and dogs. There have been many studies to identify and characterize microbes and their genes in human body. However, there was little information of microbiome in companion animals. Here, we investigated microbiota communities in feaces from twenty - four Beagles (aged 2 years old) and analyzed the taxonomy profile using metagenomics to study the difference among gut microbiome based on body condition score (BCS). gDNA was isolated from feaces, sequenced and clustered. Taxonomy profiling was performed based on the NCBI database. BCS was evaluated once a week according to the description provided by World Small Animal Veterinary Association. Firmicutes phylum was the most abundant followed by Bacteroidetes, Fusobacteria, Proteobacteria and Actinobacteria. That main microbiota in gut were differently distributed based on the BCS. Fusobacteria has been known to be associated with colon cancer in human. Interestingly, Fusobacteria was in the third level from the top in healthy dog's gut microbiome. In addition, Fusobacteria was especially higher in overweight dogs which had 6 scales of BCS. Species Fusobacterium perfoetens was also more abundant when dogs were in BCS 6. It implied that F. perfoetens would be positively related with overweight in dogs. These finding would contribute to further studies of gut microbiome and their functions to improve dog's diets and health condition.