• Asian-Australasian Journal of Animal Sciences
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• 제21권12호
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• pp.1689-1695
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• 2008

Leptin, the hormone product of the obese gene, is secreted predominately from white adipose tissue and regulates feed intake, energy metabolism and body composition. It has been considered a candidate gene for performance, carcass and meat quality traits in beef cattle. The objective of this study was to identify SNPs in the promoter region of the leptin gene and to evaluate the possible association of the SNP genotypes with carcass and meat quality traits in Korean cattle. We identified a total of 25 SNPs in the promoter region (1,208-3,049 bp upstream from the transcription start site) of the leptin gene, eleven (g.1508C>G, g.1540G>A, g.1545G>A, g.1551C>T, g.1746T>G, g.1798ins(G), g.1932del(T), g.1933del(T), g.1934del(T), g.1993C>T and g.2033C>T) of which have not been reported previously. Their sequences were deposited in GenBank database with accession number DQ202319. Genotyping of the SNPs located at positions g.2418C>G and g.2423G>A within the promoter region was performed by direct sequencing and PCR-SSCP method to investigate the effects of SNP genotypes on carcass and meat quality traits in Korean cattle. The SNP and SSCP genotypes from the two mutations of the leptin promoter were shown to be associated with the BF trait. The average BF value of animals with heterozygous SNP genotype was significantly greater than that of animals with the homozygous SNP genotypes for the g.2418C>G and g.2423G>A SNPs (p<0.05). Analysis of the combined genotype effect in both SNPs showed that animals with the AC SSCP genotype had higher BF value than animals with BB or AA SSCP genotypes (p<0.05). These results suggest that SNP of the leptin promoter region may be useful markers for selection of economic traits in Korean cattle.

• BMB Reports
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• 제52권6호
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• pp.385-390
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• 2019

Leptin, an adipokine regulating energy metabolism, appears to be associated with breast cancer progression. Insulin-like growth factor-1 (IGF-1) mediates the pathogenesis of breast cancer. The regulation of IGF-1 expression by leptin in breast cancer cells is unclear. Here, we found that leptin upregulates IGF-1 expression at the transcriptional level in breast cancer cells. Activating protein-1 (AP-1)-binding element within the proximal region of IGF-1 was necessary for leptin-induced IGF-1 promoter activation. Forced expression of AP-1 components, c-FOS or c-JUN, enhanced leptin-induced IGF-1 expression, while knockdown of c-FOS or c-JUN abrogated leptin responsiveness. All three MAPKs (ERK1/2, JNK1/2, and p38 MAPK) mediated leptin-induced IGF-1 expression. These results suggest that leptin contributes to breast cancer progression through the transcriptional upregulation of leptin via the MAPK pathway.

• Asian-Australasian Journal of Animal Sciences
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• 제18권11호
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• pp.1548-1551
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• 2005

The leptin, an anti-obesity protein, is a hormone protein expressed and secreted mainly from adipocyte tissue, and involved in regulation of body weight, food intake and energy metabolism. In an effort to discover polymorphism(s) in genes whose variant(s) might be implicated in phenotypic traits of growth, we have sequenced exons and their boundaries of leptin gene including 1,000 bp upstream of promoter region with twenty-four unrelated Korean cattle. Fifty-seven sequence variants were identified: fourteen in 5' flanking region, twenty-seven in introns, eight in exons, and eight in 3' flanking region. By pair-wise linkage analysis among polymorphisms, ten sets of SNPs were in absolute linkage disequilibrium (LD) (|D'| = 1 and $r^2$ = 1). Among variants identified, thirty-six SNPs were newly identified, and twenty-one SNPs, which were reported in other breeds, were also confirmed in Korean cattle. The allele frequencies of variants were quite different among breeds. The information from SNPs of bovine leptin gene could be useful for further genetic studies of this gene.

• 한국가축번식학회지
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• 제25권4호
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• pp.389-397
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• 2001

CART는 leptin에 의해 조절되는 포식인자이며 섭식과 운동 습성에 관계된 것으로 알려져 있다. 사람의 CART Leu34Phe 돌연변이는 비만의 표현형을 나타내었지만, 생쥐의 CART 돌연변이는 일반사료의 섭취 후 급격한 체중증가를 나타내지는 않았다 생체 내 신경세포에서 CART의 역할을 확인하기 위한 새로운 형질전환 모델을 확립하고자 분화하는 신경세포의 유전자 발현을 조절하는 NF-L promoter와 CART의 재조합 발현 벡터를 구축하였다. 형질전환 생쥐는 유전자 미세 주입법에 의하여 생산되었으며, PCR과 Southern blot의 방법으로 확인하였다. 이러한 형질전환 생쥐에서 CART의 과 발현을 수정 후 13.5일째 초기 배아와 생후 6주째 형질전환 생쥐의 뇌와 척수에서 확인하였다. 본 연구의 결과는 섭식 관련 유전자들이 상호 연관된 섭식행동에서 CART의 역할을 연구하는데 모델 동물로써 이용할 수 있을 것으로 사료된다.

• Nutritional Sciences
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• 제5권1호
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• pp.13-19
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• 2002

A mutation in the promoter region of uncoupling protein 3 (UCF3), specifically the -55C longrightarrow T transition, may influence an individual's energy metabolism and body weight. The objective of this study was to investigate the effect of a weight reduction program on endocrine functions and body fat distribution, related to UCP3 promoter genotype. Ninety overweight pre-menopausal female subjects participated in the weight reduction program at Yonsei University Hospital, and were placed on a calorie-restricted diet (300 kcal less than their daily requirements) for 12 weeks. After 12 weeks, all subjects on the program lost approximately 5% of their initial body weights and had lower Body Mass Index (BMI) values. Among the 90 women, 56 had a normal (without mutation) UCP3 genotype, while 34 women had mutations in the promoter region of UCP3. Despite similar weight reductions in both groups, a significantly higher decrease in abdominal adipose tissue was observed in the normal UCP3 genotype group, compared to the group with mutations. In particular, there was a significant reduction of fat at the lumbar 1 (Ll) level in the without-mutation group. Serum levels of total cholesterol, apolipoprotein Al were significantly decreased in the without-mutation group, by 4.4% and 5.7% respectively. Serum levels of hormones were not significantly changed in both groups artier the intervention. However, in the group without the mutations, the leptin level significantly reduced by 23.4% (p<0.001). Serum free fatty acid (FFA) concentration was significantly increased in the group with mutation following the weight reduction program. On the other hand, FFA responses were shown similar increases in both groups. In conclusion, although no difference was found in the magnitude of weight reduction in both groups, there were significant differences in body fat distribution and in endocrine function between the groups.

• 한국동물번식학회:학술대회논문집
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• 한국동물번식학회 2001년도 춘계학술발표대회
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• pp.51-51
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• 2001

Cocaine and amphetamine-regulated transcript (CART) is a satiety factor that is regulated by leptin. It was reported that the mice intracerebroventricularly injected with CART showed behavioral changes resembled with the typical behavioral alterations found in the mice carrying disorders in the brain serotonergic (5-HT) system. Hence, this study was conducted to find out the relationships between CART and 5-HT. We first examined the mRNA levels of CART after the injections of para-chlorophenylalanine (pCPA, 300 mg/kg i.p., single injection or daily for three consecutive days) in the rat brains by in situ hybridization using the mouse CART cDNA probe cloned in our laboratory. Systemic administrations of pCPA, a potent inhibitor of tryptophan hydroxylase, the rate limiting enzyme of 5-HT biosynthesis, acutely depletes the brain 5-HT transporter (5-HTT) in the dorsal raphe nucleus (DRN), which reuptakes terminal 5-HT. Results indicated that the mRNA level of CART significantly decreased in the arcuate nucleus, paraventricular nucleus, and lateral hypothalamic nucleus by three days of daily injection with pCPA with no noticeable change detected 24 hrs after the single injection. The message levels of 5-HTT in DRN decreased in both single and three days of injections. Secondly, to investigate whether CART affect to 5-HT, mouse genomic CART gene, which is consist of 3 exons and 2 introns and mouse neurofilament light (NF-L) chain promoter were cloned. Then, we constructed neuron specific expression vector, which was transfected into HeLa cell using lipid-mediated transfection system. Expression of GFP and CART linked to NF-L-chain promoter in the transfected HeLa cell were detected by using fluorescent microscope and RT-PCR. These results confirmed normal expression of DNA constructs in vitro. Then, to increase brain specific expression of CART in vivo transgenic mice carrying CART gene controlled the deleted NF-L-chain promoter were generated by the DNA microinjection into pronuclei of fertilized embryos. Transgenic mice were detected by Southern blot. Further study is necessary to examine CART expression and 5-HTT in these transgenic mice. Therefore, these results suggest that there maybe a positive molecular correlation between CART and 5-HT in responding to the stimuli.

• 한국식품영양학회지
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• 제30권3호
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• pp.531-538
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• 2017

This study was performed to investigate the effects of garlic on uncoupling protein 2 (UCP2) transcriptional regulation of UCP2-luciferase transgenic mice fed on a high fat diet to induce obesity. To examine the transcriptional regulation of UCP2, we generated transgenic mice with a UCP2 promoter (-1,830/+30 bp) containing luciferase as a reporter gene. UCP2-luciferase transgenic mice were fed a 45% high-fat diet for 8 weeks to induce obesity. Subsequently, mice were maintained on either a high-fat control diet (TG-CON), or high-fat diets supplemented with 2% (TG-GL2) or 5% (TG-GL5) garlic for a further 8 weeks. Dietary garlic reduced body weight and energy efficiency ratio in the TG-GL5 group, compared to the TG-CON group. Furthermore, garlic supplementation significantly decreased white adipose tissue fat mass and plasma levels of triglycerides, total cholesterol, and leptin in the TG-GL2 and TG-GL5 groups, compared to the TG-CON group. Specifically, UCP2 promoter activity in metabolic tissues such as liver, white adipose tissue, brown adipose tissue, and skeletal muscle was increased by garlic supplementation. These results suggest that dietary garlic was partially associated with an increase of UCP2 transcriptional activity in metabolic tissues for decreasing obesity.

• 한국가축번식학회지
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• 제24권4호
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• pp.419-428
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• 2000

랩틴은 지방세포의 비만유전자에서 분비되는 포식인자로써 음식섭취, 에너지대사, 체중, 번식생리 및 신경호르몬 분비를 조절하는 역할을 한다. 본 연구는 antisense 비만유전자를 발현하는 형질전환 생쥐를 생산하기 위하여 실시하였다. 먼저 랩틴을 분비하는 지방세포에서 RNA 를 추출한 후 역전사 PCR을 실시하여 303 bp의 anti I과 635 bp의 anti II cDNA 들을 합성하였다. 이러한 cDNA 들을 지방세포 특이적 발현 프로모터인 aP2 프로모터와 SV40 poly(A) 사이에 역방향으로 결합하여 미세주입용 유전자를 구축하였다. 생쥐의 수정란전핵에 antisense 비만유전자를 미세 주입하여 14 마리의 형질전환 생쥐를 생산하였으며, anti I 을 지닌 4 마리의 형질전환 생쥐와 anti II를 지닌 5마리의 형질전환 생쥐계통을 확립하였다. 그리고 형질전환 생쥐의 지방세포를 추출하여 RT -PCR을 실시한 결과 antisense 비만유전자 mRNA발현을 확인하였다. 따라서, 본 연구에서 생산된 형질전환생쥐는 생체 랩틴저하에 의해 비만을 일으키는 질환모텔동물로써의 사용가능성을 나타내었다.

• 한국식품영양학회지
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• 제30권5호
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• pp.900-907
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• 2017

This study was performed to investigate the body fat-lowering effect of garlic powder in peroxisome proliferator-activated receptor ${\gamma}$ coactivator-$1{\alpha}$(PGC-$1{\alpha}$)-luciferase transgenic mice (TG). In this study, we generated transgenic mice with a PGC-$1{\alpha}$ promoter (-970/+412 bp) containing luciferase as a reporter gene. Mice were fed a 45% high-fat diet for 8 weeks to induce obesity. Subsequently, mice were maintained on either a high-fat control diet (CON), or high-fat diets supplemented with 2% (GP2) or 5% (GP5) garlic powder for an additional 8 weeks. Dietary garlic powder reduced the body weight in the GP2 and GP5 groups, compared to the CON group. Furthermore, garlic supplementation significantly decreased the plasma levels of triglycerides, total cholesterol, and leptin in the GP5 group, compared to the CON group. Specifically, luciferase activity in liver, white adipose tissue (WAT), and brown adipose tissue (BAT) was increased by garlic supplementation in a dose-dependent manner. These results suggest that the body fat-lowering effect of garlic powder might be related to PGC-$1{\alpha}$ by the increase in luciferase activity in liver, WAT, and BAT. Furthermore, transgenic mice might be useful for evaluating the body fat-lowering effect of various health functional foods.