• Title/Summary/Keyword: obesity-related gene

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Assessment of Relationship between Fyn-related Kinase Gene Polymorphisms and Overweight/Obesity in Korean Population

  • Jung, Mi-Young;Kim, Bum-Shik;Kim, Youn-Jung;Koh, In-Song;Chung, Joo-Ho
    • The Korean Journal of Physiology and Pharmacology
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    • v.12 no.2
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    • pp.83-87
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    • 2008
  • The fyn-related kinase (FRK) belongs to the tyrosine kinase family of protein kinases. Recent studies have shown that Frk affects pancreatic beta cell number during embryogenesis and promotes beta cell cytotoxic signals in response to streptozotocin. To investigate the genetic association between FRK polymorphisms and the risk of obesity in Korean population, single nucleotide polymorphisms (SNPs) in the FRK gene region were selected and analyzed. The body mass index (BMI) was calculated, and biochemical data (systolic blood pressure, diastolic blood pressure, hemoglobin A1C, triglyceride, total cholesterol, high density lipoprotein, and low density lipoprotein) of blood sample from each subject were also measured. One hundred fifty five healthy control and 204 overweight/obesity subjects were recruited. Genotype frequencies of six SNPs [rs6568920 (+8391G>A), rs3756772 (+56780A>G), rs3798234 (+75687C>T), rs9384970 (+68506G>A), rs1933739 (+72978G>A), and rs9400883 (+75809A>G)] in the FRK gene were determined by Affymetrix Targeted Genotyping Chip data. According to the classification of Korean Society for the Study of Obesity, control (BMI 18 to < 23) and overweight/obesity (BMI$\geq$23) subjects were recruited. For the analysis of genetic data, EM algorithm, SNPStats, Haploview, HapAnalyzer, SNPAnalyzer, and Helixtree programs were used. Multiple logistic regression analysis (codominant, dominant, and recessive models) was performed. Age and gender as covariates were adjusted. For biochemical data, Student's t test was used. The mean value of BMI in the control and overweigh/obesity groups was 21.1${\pm}$1.2 (mean${\pm}$SD) and 25.6${\pm}$2.0, respectively. All biochemical data of the overweight/obesity group were statistically significance, compared with the control group. Among six SNPs, two linkage disequilibrium (LD) blocks were discovered. One block consisted of rs1933739 and rs9400883, and the other comprised rs3756772 and rs3798234. One SNP (rs9384970, +68506G>A) showed an association with overweight/obesity in the codominant model (p=0.03). Interestingly, the AA genotype distribution in the overweight/obesity group (n=7, 3.5%) was higher than those in the control group (n=1, 0.6%), which is not found in either Japanese or Chinese subjects. Therefore, the AA genotype of rs9384970 may be a risk factor for development of obesity in Korean population. The results suggest that FRK may be associated with overweight/obesity in Korean population.

Prediction of functional molecular machanism of Astragalus membranaceus on obesity via network pharmacology analysis (네트워크 약리학을 통한 황기의 항비만 효능 및 작용기전 예측 연구)

  • Mi Hye, Kim
    • The Korea Journal of Herbology
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    • v.38 no.1
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    • pp.45-53
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    • 2023
  • Objectives : Network pharmacology-based research is one of useful tool to predict the possible efficacy and molecular mechanisms of natural materials with multi compounds-multi targeting effects. In this study, we investigated the functional underlying mechanisms of Astragalus membranaceus Bunge (AM) on its anti-obesity effects using a network pharmacology analysis. Methods : The constituents of AM were collected from public databases and its target genes were gathered from PubChem database. The target genes of AM were compared with the gene set of obesity to find the correlation. Then, the network was constructed by Cytoscape 3.9.1. and functional enrichment analysis was conducted to predict the most relevant pathway of AM. Results : The result showed that AM network contained the 707 nodes and 6867 edges, and 525 intersecting genes were exhibited between AM and obesity gene set, indicating that high correlation with the effects of AM on obesity. Based on GO biological process and KEGG Pathway, 'Response to lipid', 'Cellular response to lipid', 'Lipid metabolic process', 'Regulation of chemokine production', 'Regulation of lipase activity', 'Chemokine signaling pathway', 'Regulation of lipolysis in adipocytes' and 'PPAR signaling pathway' were predicted as functional pathways of AM on obesity. Conclusions : AM showed high relevance with the lipid metabolism related with the chemokine production and lipolysis pathways. This study could be a basis that AM has promising effects on obesity via network pharmacology analysis.

Adipocyte-Related Genes and Transcription Factors were Affected by siRNA for Aromatase Gene during 3T3-L1 Differentiation (지방세포 분화중인 3T3-L1 세포에서 아로마테이즈 siRNA 처리에 의한 지방관련 유전자와 전사인자의 발현 조절)

  • Jeong, Dong-Kee
    • Journal of Life Science
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    • v.18 no.11
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    • pp.1600-1605
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    • 2008
  • This study was performed to verify the gene expression of 3T3-L1 using the siRNA of the aromatase gene, which is the estrogen synthesis enzymes. First of all three pairs of siRNA were designed from the CYP19A1 (aromatase) and analyzed the formation of fat cell mechanism by transferring gene to 3T3-L1 and differentiating it. As a result, the expression of leptin gene, which is the main gene causing the obesity, was controlled and the cause of the obesity is related with the insulin specifically. The overexpression of adiponectin and adipsin was observed. This result showed that the formation of the fat was controlled a little without any side effect by obstructing a specific material out of all the signal systems in the fat formation. This study will be an important clue to make it clear that the lack or overexpression of estrogen might be the cause of fat formation mechanism.

Replication of Early B-cell Factor 1 (EBF1) Gene-by-psychosocial Stress Interaction Effects on Central Adiposity in a Korean Population

  • Kim, Hyun-Jin;Min, Jin-Young;Min, Kyoung-Bok
    • Journal of Preventive Medicine and Public Health
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    • v.49 no.5
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    • pp.253-259
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    • 2016
  • Objectives: Central obesity plays a major role in the development of many chronic diseases, including cardiovascular disease and cancer. Chronic stress may be involved in the pathophysiology of central obesity. Although several large-scale genome-wide association studies have reported susceptibility genes for central adiposity, the effects of interactions between genes and psychosocial stress on central adiposity have rarely been examined. A recent study focusing on Caucasians discovered the novel gene early B-cell factor 1 (EBF1), which was associated with central obesity-related traits via interactions with stress levels. We aimed to evaluate EBF1 gene-by-stress interaction effects on central adiposity traits, including visceral adipose tissue (VAT), in Korean adults. Methods: A total of 1467 Korean adults were included in this study. We selected 22 single-nucleotide polymorphisms (SNPs) in the EBF1 gene and analyzed their interactions with stress on central adiposity using additive, dominant, and recessive genetic modeling. Results: The four SNPs that had strong linkage disequilibrium relationships (rs10061900, rs10070743, rs4704967, and rs10056564) demonstrated significant interactions with the waist-hip ratio in the dominant model ($p_{int}$<0.007). In addition, two other SNPs (rs6556377 and rs13180086) were associated with VAT by interactions with stress levels, especially in the recessive genetic model ($p_{int}$<0.007). As stress levels increased, the mean values of central adiposity traits according to SNP genotypes exhibited gradual but significant changes (p<0.05). Conclusions: These results suggest that the common genetic variants for EBF1 are associated with central adiposity through interactions with stress levels, emphasizing the importance of managing stress in the prevention of central obesity.

Suppressive Effects of By-Product Extracts from Soybean on Adipocyte Differentiation and Expression of Obesity-Related Genes in 3T3-L1 Adipocytes (대두부산물의 지방세포분화 유도유전자의 발현저해 및 전지방세포 분화 억제 효과)

  • Choi, Mi-Sun;Kim, Jee-In;Jeong, Jin-Boo;Lee, Su-Bok;Jeong, Jae-Nam;Jeong, Hyung-Jin;Seo, Eul-Won;Kim, Taek-Yoon;Kwon, Oh-Jun;Lim, Jae-Hwan
    • Journal of Life Science
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    • v.21 no.3
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    • pp.358-367
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    • 2011
  • Soybean is known to contain various phytochemicals that are related to anti-oxidant, anti-inflammatory and anti-obesity effects in mice and humans. The anti-obesity effect of by-product extracts from soybean on the differentiation of 3T3-L1 pre-adipocytes to adipocytes was investigated by suppressing adipocyte differentiation and lipid accumulation with Oil Red-O assay and quantitative PCR. In inducing differentiation of 3T3-L1 pre-adipocytes in the presence of an adipogenic cocktail, isobutylmethylanthine (IBMX), dexamathasone, and insulin, treatment with filtrated soybean soaked water, soybean milk, and soycurd residue from soybean curd processing significantly decreased mRNA expression of obesity-related gene such as PPAR${\gamma}$, Fabp4, and Scd1, adipsin, apolipoprotein (APOE) and adiponectin (ADIPOQ) without any significant cytotoxicity. We also determined the well-known isoflavones in soybean, such as daidzein and genistein, in the by-product extracts. Taken together, we suggest that soybean by-product extract showed anti-obesity effect by suppressing adipocyte related gene expression, and that by-products collected during soybean curd processing may be a good candidate as an ingredient in health care products.

Effects of Hwanggimacmundong-tang on Body Weight and Gene Expression in Obese Rats with Estrogen Deficiency (황기맥문동탕이 에스트로겐 결핍 Rat의 체중 변화와 비만 관련 유전자 발현에 미치는 영향)

  • Lee, Hye-In;Yoo, Dong-Youl;Yoo, Jeong-Eun
    • The Journal of Korean Obstetrics and Gynecology
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    • v.31 no.2
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    • pp.49-67
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    • 2018
  • Objectives: This study was conducted to assess the effects of Hwanggimacmundong-tang extract (HM) on obese rats with estrogen deficiency. Methods: The experiments were performed with ovariectomized rats as estrogen-deficient obesity model. Rats were grouped NC (Normal Control Group; sham operation group), OC (Obesity Control Group; estrogen-deficient group), HML (20 mg/kg/day), HMH (100 mg/kg/day). HM was administered orally for six weeks. Body weights and serum lipid level were measured, and real-time PCR was performed to estimate the effect of HM on gene expression in liver. Results: HM decreased the total cholesterol and triglyceride in serum. And HM increased leptin, CPT1 gene expression in liver tissue of obese rats with estrogen deficiency. However HM decreased $PPAR{\gamma}$, $PGC-1{\alpha}$, HMGCR, CYP8B1, LPL, ACAT1, ACAT2, ApoB, ACOX gene expression in liver tissue of obese rats with estrogen deficiency. Conclusions: It is concluded that HM reduced total cholesterol and triglyceride in serum, and regulate gene expression related to lipid metabolism. These results indicate Hwanggimacmundong-tang that might have potential for treatment of obesity and complications during the menopause caused by estrogen-deficiency.

Global DNA Methylation Patterns and Gene Expression Associated with Obesity-Susceptibility in Offspring of Pregnant Sprague-Dawley Rats Exposed to BDE-47 and BDE-209 (임신 중 BDE-47 및 BDE-209에 노출된 어미와 새끼 Sprague-Dawley 랫드의 Global DNA 메틸화 양상과 비만 감수성과 연관된 유전자 발현)

  • Park, Byeong-Min;Yoon, Ok-Jin;Lee, Do-Hoon
    • Korean Journal of Clinical Laboratory Science
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    • v.49 no.1
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    • pp.28-39
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    • 2017
  • Persistent organic pollutants (POPs) can affect epigenetic mechanisms and obesity development. Polybrominated diphenyl ethers (PBDEs)-widely used to make flames-are one of the important POPs. Prenatal exposure to endocrine disrupting chemicals (EDCs), such as POPs, may affect global DNA methylation in long interspersed nuclear elements (LINE-1), increasing the risk of obesity later in life. Therefore, pregnant Sprague-Dawley (SD) rats were used to elucidate whether BDE-47 and BDE-209 transferred through placenta and breast milk cause epigenetic changes in LINE-1 and increase genetic susceptibility to obesity as obesogen during the developmental periods. Global DNA methylation in LINE-1 and gene expression related to obesity were measured in dams and offspring, using a methylation-sensitive high resolution melting analysis (MS-HRM) and direct bisulfite sequencing and quantitative real time polymerase chain reaction (qPCR), respectively. The results of MS-HRM showed global DNA hypomethylation patterns in LINE-1 of exposed offspring (2 of total 4) at PND 4, but bisulfite sequencing showed no difference in both the exposed and non-exposed groups. Gene expression in dams related to ${\beta}$-oxidation pathway and those related to adipokines showed different patterns between the two groups. On the contrary, gene expressions of offspring showed a similar pattern. Gene expressions related to ${\beta}$-oxidation pathway and obesity were significantly increased when compared with 'at birth', but not $PPAR-{\alpha}$. In conclusion, this study demonstrated the possibility that co-exposure to BDE-47 and BDE-209-via the placenta and breast milk-may affect epigenetic changes and modulate gene expression levels related to obesity.

Anticancer(AC)-Functional Kimchi Exhibits Antiobesity Effects in Differentiated 3T3-L1 Adipocytes

  • Park, Eui-Seong;Lee, Seung-Min;Lim, Yaung-lee;Park, Kun-Young
    • CELLMED
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    • v.8 no.3
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    • pp.11.1-11.6
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    • 2018
  • In vitro anti-obesity effects of anti-cancer (AC) functional kimchi in differentiated 3T3-L1 adipocytes were studied. We constructed three experimental groups: Control, standardized kimchi (SK), and AC functional kimchi (A-FK) that included active ingredients and Lactobacillus plantarum. Kimchi extracts did not show any cytotoxicity in pre-adipocytes in the concentration range of 1 - 5 mg/mL. A-FK significantly reduced fat droplet formation and absorbance in differentiated 3T3-L1 adipocytes, as shown by Oil red O staining, compared to Control and SK (P < 0.05). SK and A-FK reduced adipo-/lipogenesis related genes such as $C/EBP{\alpha}$, SREBP-1, LPL, and $LXR{\alpha}$ compared to Control (P < 0.05). Especially, A-FK more greatly reduced SREBP-1 and LPL compared to SK (P < 0.05). A-FK up-regulated the ${\beta}$-oxidation related gene CPT-1c and down-regulated the pro-inflammatory cytokine IL-6 compared to Control (P < 0.05). Based on the results, A-FK exhibited anti-obesity effects by inhibiting fat droplet formation and adipo-/lipogenesis related genes by regulating the ${\beta}$-oxidation related gene CPT-1c and pro-inflammatory cytokine IL-6. In previous studies, A-FK kimchi already exhibited a strong anti-cancer effect. These results indicate that A-FK increased anti-obesity activity in this model system due to its functional ingredients and anti-cancer functionality.

Chitinase 3-Like 1 (CHI3L1) Polymorphism Contributes to Visceral Obesity and Obesity-related Inflammation Induces Chi3l1 in Adipocytes

  • Kim, A Young;Jeong, Hyun Woo;Lee, Ji-Hae;Choi, Jin Kyu;Kim, Jeong Kee;Hwang, Jae Sung;Seo, Dae-Bang
    • Biomedical Science Letters
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    • v.24 no.1
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    • pp.23-29
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    • 2018
  • Abdominal obesity is considered as one of the most risky factors governing the development of metabolic diseases. Here we identify that human chitinase 3-like 1 (CHI3L1, also called YKL-40 in human) single nucleotide polymorphism (SNP), rs883125, is associated with abdominal obesity in Korean women. Korean women subjects with the rs883125 G/G or C/G genotype present higher waist-hip ratio than subjects with C/C genotype suggesting that human subjects who G nucleotide substitution at the rs883125 tended to more accumulate intra-abdominal fat at the abdominal cavity. In addition, Chi3l1 gene expression is increased in adipose tissue from obese mice and pro-inflammatory cytokine enhances Chi3l1 expression in adipocytes, indicating that Chi3l1 is greatly related with obesity and obesity-induced pro-inflammatory responses. Taken together, the minor allele of rs883125 is associated with a higher prevalence of abdominal obesity in Korean women. These findings suggest that genotype of rs883125 can be a biomarker of incident abdominal obesity and abdominal obesity-related metabolic diseases.

Current Trends in Nutrigenomics (영양유전체학(Nutrigenomics)의 최근 경향)

  • Choi, Bong-Hyuk;Kim, Jong-Bae;Do, Myoung-Sool
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.34 no.10
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    • pp.1642-1654
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    • 2005
  • With the decoding of human genome in 2004 and the recent development in nutritional science there has been an integration of molecular biology and nutrition. As a consequenc a now word ' molecular nutrition ' has been formed and recently the word 'nutrigenomics' is coined and widely being used. The field of science that showed the most positive result from grafting the science of nutrition and nutrigenomics is obesity. In 1994, Jeffrey Friedman from Rockeffeler University announced that ob gene and obesity has a close relationship and since then there's been a huge research done on genes related to obesity from the molecular nutrition's Point of view. Even now there are many genes presented which are supposed to be related to obesity and big efforts are put into finding what exactly those genes do. Moreover studying only in the context of genes was not enough so functional genomics, which is the study of the functions of cells and the functions and effects between genes and Protein Products, is being studied. This review article discusses the relationship between nutrition and genes and the general idea of nutrigenomics. The article also discusses about the current research status on these subjects.