• 약학회지
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• 제44권5호
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• pp.391-398
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• 2000

Leptin, the product of the ob gene, is a small peptide molecule synthesized by white adipocytes with an important role in the regulation of body fat and food intake. Based on the evidence that synthesis of leptin is regulated by female sex hormone, estrogen, this present study was investigated whether sex hormone precursor DHEA, can regulate obese gene expression in lean and genetically obese (ob/ob) mice. Antiobesity activity of DHEA was evaluated by determining body weight, food consumption, epididymal fat weight and serum levels of cholesterol and triglyceride in ICR, C57BL/6J, and ob/ob mice. The treatment of C57BL/6J lean and obese mice with a diet containing 0.3% and 0.6% DHEA resulted in lowered rates of weight gain in comparison to non-treated mice, although much greater response was found in the obese mice. All other concentrations of DHEA (0.015%, 0.06%, 0.15%, 0.3%) except the highest one(0.6%) showed no significant effects on weight gain in ICR mice. Food consumption was significantly decreased in all mice treated with 0.6% DHEA, whereas it was not decreased in ICR mice at lower concentrations than 0.6% DHEA. DHEA decreased significantly epididymal adipose tissue weight and serum triglyceride levels dose dependently in lean and obese mice. However serum cholesterol levels were decreased at lower concentrations than 0.15% DHEA and increased at concentrations of 0.3% and 0.6% DHEA in lean and obese mice. These increases in serum cholestrol levels at high concentrations of DHEA might result from the fact that DHEA has a cholesterol moiety thereby interfered the assay system. As an approach to elucidate the mechanism for antiobesity activity of DHEA, we examined mRNA levels of obese gene in the adipocyte and obese gene product (leptin) in the serum. The results showed that DHEA did not affect obese gene expression in ICR and C57BL/6J mice. Therefore, we concluded that antiobesity activity of DHEA was not modulated by obese gene expression.

• Biomolecules & Therapeutics
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• 제27권1호
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• pp.107-116
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• 2019

The global obesity epidemic and associated metabolic diseases require alternative biological targets for new therapeutic strategies. In this study, we show that a phytochemical sulfuretin suppressed adipocyte differentiation of preadipocytes and administration of sulfuretin to high fat diet-fed obese mice prevented obesity and increased insulin sensitivity. These effects were associated with a suppressed expression of inflammatory markers, induced expression of adiponectin, and increased levels of phosphorylated ERK and AKT. To elucidate the molecular mechanism of sulfuretin in adipocytes, we performed microarray analysis and identified activating transcription factor 3 (Atf3) as a sulfuretin-responsive gene. Sulfuretin elevated Atf3 mRNA and protein levels in white adipose tissue and adipocytes. Consistently, deficiency of Atf3 promoted lipid accumulation and the expression of adipocyte markers. Sulfuretin's but not resveratrol's anti-adipogenic effects were diminished in Atf3 deficient cells, indicating that Atf3 is an essential factor in the effects of sulfuretin. These results highlight the usefulness of sulfuretin as a new anti-obesity intervention for the prevention of obesity and its associated metabolic diseases.

• Journal of Ginseng Research
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• 제46권3호
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• pp.454-463
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• 2022

Background: Gintonin-enriched fraction (GEF), a non-saponin fraction of ginseng, is a novel glycolipoprotein rich in hydrophobic amino acids. GEF has recently been shown to regulate lipid metabolism and browning in adipocytes; however, the mechanisms underlying its effects on energy metabolism and whether it affects sarcopenic obesity are unclear. We aimed to evaluate the effects of GEF on skeletal muscle atrophy in high-fat diet (HFD)-induced obese mice. Methods: To examine the effect of GEF on sarcopenic obesity, 4-week-old male ICR mice were used. The mice were divided into four groups: chow diet (CD), HFD, HFD supplemented with 50 mg/kg/day GEF, or 150 mg/kg/day GEF for 6 weeks. We analyzed body mass gain and grip strength, histological staining, western blot analysis, and immunofluorescence to quantify changes in sarcopenic obesity-related factors. Results: GEF inhibited body mass gain while HFD-fed mice gained 22.7 ± 2.0 g, whereas GEF-treated mice gained 14.3 ± 1.2 g for GEF50 and 11.8 ± 1.6 g for GEF150 by downregulating adipogenesis and inducing lipolysis and browning in white adipose tissue (WAT). GEF also enhanced mitochondrial biogenesis threefold in skeletal muscle. Furthermore, GEF-treated skeletal muscle exhibited decreased expression of muscle-specific atrophic genes, and promoted myogenic differentiation and increased muscle mass and strength in a dose-dependent manner (p < 0.05). Conclusion: These findings indicate that GEF may have potential uses in preventing sarcopenic obesity by promoting energy expenditure and attenuating skeletal muscle atrophy.

• 대한의용생체공학회:의공학회지
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• 제45권1호
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• pp.43-48
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• 2024

The prevalence of obesity and its complications is steadily increasing worldwide. It is essential to understand cellular level metabolism and microenvironment to treat diseases related to lipid metabolism. Mechanical loading can activate signaling pathway by stimulating cells, especially vibration loading known to inhibit adipogenesis, so it has been studied as a treatment for obesity. Also, vibration loading can affect the inside of the human body non-invasively. Another clue to reducing adipose tissue is browning, which means that white adipocytes changes to brown adipocyte. In this study, we design and developed a device that that can control cell-cell contact, and vibration simulation device. Using these two devices, we investigated responses of cells to vibration loading. Protein expression associated with browning and adipogenesis were analyzed. In conclusion, vibration loading can be transmitted through cell contact and loading applied to the cells can induce browning and inhibit adipogenesis of preadipocytes. These results suggest the possibility that vibrations could be a treatment for obesity.

• Nutrition Research and Practice
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• 제18권1호
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• pp.46-61
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• 2024

BACKGROUND/OBJECTIVES: An increasing life expectancy in society has burdened healthcare systems substantially because of the rising prevalence of age-related metabolic diseases. This study compared the effects of animal protein hydrolysate (APH) and casein on metabolic diseases using aged mice. MATERIALS/METHODS: Eight-week-old and 50-week-old C57BL/6J mice were used as the non-aged (YC group) and aged controls (NC group), respectively. The aged mice were divided randomly into 3 groups (NC, low-APH [LP], and high-APH [HP] and fed each experimental diet for 12 weeks. In the LP and HP groups, casein in the AIN-93G diet was substituted with 16 kcal% and 24 kcal% APH, respectively. The mice were sacrificed when they were 63-week-old, and plasma and hepatic lipid, white adipose tissue weight, hepatic glucose, lipid, and antioxidant enzyme activities, immunohistochemistry staining, and mRNA expression related to the glucose metabolism on liver and muscle were analyzed. RESULTS: Supplementation of APH in aging mice resulted in a significant decrease in visceral fat (epididymal, perirenal, retroperitoneal, and mesenteric fat) compared to the negative control (NC) group. The intraperitoneal glucose tolerance test and area under the curve analysis revealed insulin resistance in the NC group, which was alleviated by APH supplementation. APH supplementation reduced hepatic gluconeogenesis and increased glucose utilization in the liver and muscle. Furthermore, APH supplementation improved hepatic steatosis by reducing the hepatic fatty acid and phosphatidate phosphatase activity while increasing the hepatic carnitine palmitoyltransferase activity. Furthermore, in the APH supplementation groups, the red blood cell (RBC) thiobarbituric acid reactive substances and hepatic H₂O₂ levels decreased, and the RBC glutathione, hepatic catalase, and glutathione peroxidase activities increased. CONCLUSIONS: APH supplementation reduced visceral fat accumulation and alleviated obesity-related metabolic diseases, including insulin resistance and hepatic steatosis, in aged mice. Therefore, high-quality animal protein APH that reduces the molecular weight and enhances the protein digestibility-corrected amino acid score has potential as a dietary supplement for healthy aging.

• The Korean Journal of Physiology and Pharmacology
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• 제17권5호
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• pp.455-461
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• 2013

Retinoids regulate not only various cell functions including proliferation and differentiation but also glucose and lipid metabolism. After we observed a marked up-regulation of cellular retinol-binding protein-I (CRBP-I) in the liver of hepatitis B virus x antigen (HBx)-transgenic (HBx Tg) mice which are prone to hepatocellular carcinoma (HCC) and fatty liver, we aimed to evaluate retinoid pathway, including genes for the retinoid physiology, CRBP-I protein expression, and retinoid levels, in the liver of HBx Tg mice. We also assessed the effect of chronic metformin treatment on HCC development in the mice. Many genes involved in hepatic retinoid physiology, including CRBP-I, were altered and the tissue levels of retinol and all-trans retinoic acid (ATRA) were elevated in the liver of HBx Tg mice compared to those of wild type (WT) control mice. CRBP-I protein expression in liver, but not in white adipose tissue, of HBx Tg mice was significantly elevated compared to WT control mice while CRBP-I protein expressions in the liver and WAT of high-fat fed obese and db/db mice were comparable to WT control mice. Chronic treatment of HBx Tg mice with metformin did not affect the incidence of HCC, but slightly increased hepatic CRBP-I level. In conclusion, hepatic CRBP-I level was markedly up-regulated in HCC-prone HBx Tg mice and neither hepatic CRBP-I nor the development of HCC was suppressed by metformin treatment.

• Journal of Acupuncture Research
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• 제27권6호
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• pp.31-42
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• 2010

Objectives : The aim of this study was to investigate the anti-obesity potential and mechanisms of action of Rhizoma Atractylodis(RA) herbal acupuncture in high fat diet- induced obese ICR mice. Methods : Sample solutions for herbal acupuncture were prepared from the Rhizoma Atractylodis water extract powder at concentration of 150mg/kg and 300mg/kg with distilled water. Five week-old ICR mice acclimatized to the laboratory environment for 1 week were allocated into four groups: regular diet group (RD), high fat diet group(HFD), groups fed HFD with 150mg/kg RA herbal acupuncture treatment (RAE 150) and with 300mg/kg RA herbal acupuncture treatment(RAE 300). Herbal acupuncture groups were injected with either 150mg/kg or 300mg/kg of Rhizoma Atractylodis(RA) subcutaneously onto both Sinsu($BL_{23}$) alternately on the same time everyday for 30days. Body weight, gross appearance of epididymal fat area, blood glucose, insulin, insulin resistance(HOMA-IR), non-esterified fatty acid, cholesterol, triglyceride, AST, ALT, histological analysis of white adipose tissue, gene expression responsible for adipocyte differentiation and AMPK activation were analyzed. Results : RA herbal acupuncture inhibited the development of weight gain, hyperglycemia, hyperinsulinemia, hyperlipidemia, increases of AST and ALT, and the enlargement of fat cell size induced by HFD. Also, RA herbal acupuncture inhibited the expression of PPAR-${\gamma}$, C/$EBP{\alpha}$, aP2, LPL, FAS, SCD-1 and enhanced the activation of AMP-activated protein kinase. Conclusions : The results of this study demonstrate that RA herbal acupuncture can exert the anti-obesity effect and it is partially mediated by activation of AMPK and inhibition of the gene expressions responsible for adipocyte differentiation. Further studies will be required to ascertain the nti-obesity effect and mechanisms of action of RA herbal acupuncture in animal models and human for aclinical application.

• Nutrition Research and Practice
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• 제5권3호
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• pp.198-204
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• 2011

Target herbal ingredient (THI) is an extract made from two herbs, Scutellariae Radix and Platycodi Radix. It has been developed as a treatment for metabolic diseases such as hyperlipidemia, atherosclerosis, and hypertension. One component of these two herbs has been reported to have anti-inflammatory, anti-hyperlipidemic, and anti-obesity activities. However, there have been no reports about the effects of the mixed extract of these two herbs on metabolic diseases. In this study, we investigated the metabolic effects of THI using a diet-induced obesity (DIO) mouse model. High-fat diet (HFD) mice were orally administered daily with 250 mg/kg of THI. After 10 weeks of treatment, the THI-administered HFD mice showed reduction of body weights and epididymal white adipose tissue weights as well as improved glucose tolerance. In addition, the level of total cholesterol in the serum was markedly reduced. To elucidate the molecular mechanism of the metabolic effects of THI in vitro, 3T3-L1 cells were treated with THI, after which the mRNA levels of adipogenic transcription factors, including C/$EBP{\alpha}$ and $PPAR{\gamma}$, were measured. The results show that the expression of these two transcription factors was down regulated by THI in a dose-dependent manner. We also examined the combinatorial effects of THI and swimming exercise on metabolic status. THI administration simultaneously accompanied by swimming exercise had a synergistic effect on serum cholesterol levels. These findings suggest that THI could be developed as a supplement for improving metabolic status.

• Journal of Nutrition and Health
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• 제53권2호
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• pp.99-110
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• 2020

본 연구에서는 고기능성 쌀인 큰눈자미 배아의 phytosterols 함량 및 in vitro 항산화 활성을 평가하고, 성숙기 흰쥐에게 보충 급여한 당질 대사, 항산화 활성 및 일부 cytokines 개선 효과 여부를 검증하였다. Phytosterols 분석에서 NG보다 KG의 campesterol과 stigmasterol의 함량이 유의하게 높았다. NG에 비해 KG가 DPPH radical 소거 활성, 환원력 및 ABTS radical 소거능 측정에서 유의적으로 높은 값을 나타내었다. 실험동물은 각 10마리씩 3군으로 나누어 일반 식이를 급여하는 NC군, 일반현미배아 3%를 첨가하는 NG3군, 큰눈자미배아 3%를 첨가하는 KG3군으로 나누어 사육하였다. 그 결과 KG3군에서 체중증가량, 신장주위 및 총 지방량이 유의하게 감소하였다. 당질 대사에서 실험군들 간에 glucose, 인슐린, C-peptide 및 HOMA-IR의 수준이 유의적인 차이가 나타나지 않았다. KG3군에서 혈중 TNF-α 수준이 NG3에 비해 유의적으로 감소하고, SOD 활성이 유의하게 증가하였으며, leptin, AOPP 및 IL-6 수준이 감소하는 경향을 나타내었다. 이상의 결과로부터 큰눈자미 배아는 높은 함량의 phytosterols과, 우수한 in vitro 항산화활성, 그리고 in vivo 실험에서 일부의 cytokine 개선 및 항산화에 긍정적인 효과가 있음을 제시하였고 향후 더 많은 생리활성물질 분석, 대사 지표 개선, 작용 기전 규명 등 세부적인 연구가 필요할 것으로 사료된다.

• 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.