• Biomedical Science Letters
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• v.23 no.2
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• pp.144-153
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• 2017

It was demonstrated that Gangjihwan (DF), which is the herbal composition composed of Ephedra intermedia, Lithospermum erythrorhizon, and Rheum palmatum, inhibits obesity and hepatic steatosis in high fat diet (HFD)-fed obese mice. The aim of this study was to determine the effects of DF on visceral obesity, hepatic inflammation and fibrosis and the mechanism of actions involved in this process using in vivo and in vitro approaches. DF was extracted with water (DF-FW), 30% grain alcohol (DF-GA30), and 70% grain alcohol (DF-GA70). Administration of DF to HFD-fed control mice decreased visceral tissue mass and visceral adipocyte size without adverse effects. Visceral fat mass was decreased by DF-GA30 and DF-GA70, and visceral adipocyte size by all three DF extracts compared with obese control mice. Histological analysis revealed that three kinds of DF extracts reduced toluidine blue-stained mast cells and collagen accumulation in the liver, the extents of which were most eminent in DF-GA70-treated mice. DF-GA70 decreased the mRNA levels of the inflammation ($TNF{\alpha}$ and VCAM-1), fibrosis (${\alpha}-SMA$), and apoptosis (caspase 3) genes, but increasing the anti-apoptosis gene (Bcl-2) mRNA levels in the liver of obese control mice. Consistent with the in vivo data, GA-70 also altered the expression of inflammation genes ($TNF{\alpha}$ and MCP-1) in HepG2 cells. These results indicate that DF not only inhibits visceral obesity, but also ameliorates visceral obesity-induced hepatic inflammation and fibrosis and that this process may be mediated by regulating the hepatic expression of inflammatory and fibrogenic genes.

• Korean Journal of Plant Resources
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• v.29 no.1
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• pp.1-10
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• 2016

Obesity is a pro-inflammatory state that contributes to the development of metabolic disorders such as hyperlipidemia, insulin resistance, type 2 diabetes, non-alcoholic fatty liver, and cardiovascular disease. In this study, we evaluated the inhibition of adipogenesis in 3T3-L1 cells and in high-fat diet (HFD)-induced obese mice by Peucedanum japonicum Thunberg L. water extract (PJT). Lipid accumulation measurement indicates that PJT markedly inhibited adipogenesis in a dose-dependent manner. RT-PCR results demonstrated that the mRNA expression of adipogenic transcription factors such as peroxisome proliferator-activated receptor-γ (PPARγ) and CCAAT/enhancer binding protein-α (C/EBPα) in 3T3-L1 cells were significantly down-regulated by PJT treatment. Oral administration of PJT (100, 300, and 500 ㎎/㎏, b.w/daily for 4 weeks) was conducted in high-fat diet induced obese mice and C57BL/6 mice. The PJT-administered group of HFD-induced mice had a lower body weight gain, along with decreased serum levels of glucose, triglycerides, and total cholesterol compared with the control mice, however, the HDL-cholesterol/total cholesterol ratio was increased. Furthermore, the elevated mRNA expression levels of adipogenesis related genes in the white adipose tissue of obese mice were significantly suppressed by PJT. These results indicate that PJT exhibits anti-obesity effects in obese mice by decreasing in serum lipid levels and lipogenesis related gene.

• Journal of Applied Biological Chemistry
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• v.58 no.2
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• pp.195-195
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• 2015

• Journal of the Korean Applied Science and Technology
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• v.37 no.5
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• pp.1125-1137
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• 2020

This study investigated whether swimming exercise suppresses(: inhibites) the inflammatory response in adipose tissue in obese mice induced by a high fat diet after ovariectomy in female mice. Experimental group and control group were divided into sham-opereated group (Sham), ovariectomized group (OVX), and ovariectomized group with swimming exercise (OVX/Ex). All female mice fed high fat diet (45% fat) for 8 weeks. Compared with the Sham, the OVX increased the weight of visceral adipose tissue including parametrial, retroperitoneal, and mesenteric adipose tissue. Compared to the OVX, the OVX/Ex demonstrated reductions the weight of visceral adipose tissue. Compared to the Sham, the OVX decreased the mRNA expression of IκBα and increased the mRNA expression of inflammatory cytokines (L-6, MCP-1, TNF-α and leptin) in adipose tissue. But the OVX/Ex appeared to increase the mRNA expression of IκBα and decrease the mRNA expression of inflammatory cytokines in adipose tissue, compared with the OVX. This findings suggested that swimming exercise is useful for preventing adipose tissue inflammation, which will be effective in the prevention and treatment of obesity in obese mice induced obesity by a high fat diet after ovariectomy.

• Journal of the Korean Applied Science and Technology
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• v.36 no.3
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• pp.876-884
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• 2019

We investigated the effect of moderate- and high-intensity resistance training on hippocampal neurotrophic factors and peripheral CCL11 levels in high-fat diet (HFD)-induced obese mice. C57/black male mice received a 4 weeks diet of normal (control, CON; n = 9) or a high-fat diet (HF; n = 27) to induce obesity. Thereafter, the HF group was subdivided equally into the HF, HF + moderate-intensity exercise (HFME), and HF + high-intensity exercise (HFHE) groups (n = 9, respectively), and mice were subjected to ladder-climbing exercise for 8 weeks. The hippocampal brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) levels were significantly lower in the HF group than in the CON group (p < 0.05). In addition, in the HFME and HFHE groups were significantly higher than in the HF group (p < 0.05). The peripheral CCL11 levels were significantly higher in the HF group than in the CON group (p < 0.05). In addition, in the HFME and HFHE groups were significantly lower than in the HF group (p < 0.05). However, there was no significant difference according to the exercise intensity among the groups. Collectively, these results suggest that obesity can induce down-regulation of neurotrophic factors and inhibition of neurogenesis. In contrast, regardless of exercise intensity, resistance training may have a positive effect on improving brain function by inducing increased expression of neurotrophic factors.

• Journal of the Korean Society of Food Science and Nutrition
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• v.38 no.11
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• pp.1522-1527
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• 2009

We investigated the effects of feeding diet containing medicinal plant water extracts (MPWEs) on body weight, epididymal adipose tissue weight, adipocyte size of epididymal adipose tissue and plasma lipid levels in high fat (HF) diet-induced obese mice. To test antiobese effects of diet containing the MPWEs, C57BL/6J mice were fed with HF diet for 11 weeks. In the last 6 weeks, the HF diet was supplemented with 0 (HFD) or MPWEs (5 g/kg, HFD＋MPWEs) or orlistat [0.5 g/kg, HFD＋orlistat (antiobesity drug)]. The HF-free diet group was fed normal chow for 11 weeks. Eleven-weeks feeding with HFD resulted in significant increase in lipid levels, body weight, liver and epididymal adipose tissue weights, compared with the HF-free group. Diet containing MPWEs significantly reduced plasma total cholesterol, LDL-cholesterol, triglyceride and glucose concentrations as well as body weight, liver weight and epididymal adipose tissue weight. Plasma triglyceride levels were significantly lower in the HFD＋Forlistat group after 6 weeks and a similar effect was found with HFD＋MPWEs group. The adipocyte size of epididymal adipose tissue in HFD group was significantly larger than those of HF-free group. MPWEs and orlistat (positive control) significantly decreased the size of epididymal adipocytes but orlistat was slightly more effective than MPWEs. These results suggest that oral feeding of the MPWEs may have antiobesity effects by suppressing body weight gain, adipose tissue formation and adipocyte size increase.

• Journal of Korean Medicine Rehabilitation
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• v.21 no.1
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• pp.1-22
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• 2011

Objectives : This study was undertaken to verify the effects of Wolbigachul-tang1(WBCEx1) on obesity using high fat diet-induced male mice and to investigate the molecular mechanisms involved. Methods : 8-week old C57BL/6 mice were divided into 5 groups; lean control, obese control, WBCEx1, 2, 3. After mice were treated with WBCEx1(water extract), 2(30% ethanol extract), 3(water extract; Ephedra sinica Stapf., Gypsum fibrosum) for 12 weeks, body weight gain, feeding efficiency ratio, plasma lipid and glucose metabolism, the messenger RNA(mRNA) expression of peroxisome proliferator activated receptor(PPAR)$\alpha$ target genes were measured. In addition, $PPAR{\alpha}$ target gene expression was examined in liver, white adipose tissue and skeletal muscle. Results : 1. WBCEx1-treated mice had significantly lower body weight gain and feeding efficiency ratio. 2. Consistent with the effects on body weight gain, WBCEx1 decreased the weights of epididymal and retroperitoneal white adipose tissue, inguinal subcutaneous adipose tissue, and brown adipose tissue. 3. WBCEx1 significantly decreased plasma triglyceride and total cholesterol levels. 4. The size of adipocytes were significantly decreased by WBCEx1, whereas the adipocyte number per unit area was increased. Hepatic lipid accumulation was decreased by WBCEx1. 5. WBCEx1 did not affect the mRNA expression of $PPAR{\alpha}$ target genes in liver, adipose tissue, and skeletal muscle. 6. Plasma asparate aminotransferase(AST), alanine aminotransferase(ALT), blood urea nitrogen(BUN) and creatine concentrations were in the physiological range. Liver and kidney weights were significantly lower following WBCEx treatment compared with obese controls, indicating that WBCEx does not show any toxic effects on liver and kidney. Conclusions : These results suggest that WBCEx1-induced body weight reduction is associated with appetite control and mediated by a mechanism other than the activation of $PPAR{\alpha}$.

• BMB Reports
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• v.54 no.8
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• pp.419-424
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• 2021

Cold-induced norepinephrine activates β3-adrenergic receptors (β3-AR) to stimulate the kinase cascade and cAMP-response element-binding protein, leading to the induction of thermogenic gene expression including uncoupling protein 1 (Ucp1). Here, we showed that stimulation of the β3-AR by its agonists isoproterenol and CL316,243 in adipocytes increased the expression of Ucp1 and Heme Oxygenase 1 (Hmox1), the principal Nrf2 target gene, suggesting the functional interaction of Nrf2 with β3-AR signaling. The activation of Nrf2 by tert-butylhydroquinone and reactive oxygen species (ROS) production by glucose oxidase induced both Ucp1 and Hmox1 expression. The increased expression of Ucp1 and Hmox1 was significantly reduced in the presence of a Nrf2 chemical inhibitor or in Nrf2-deleted (knockout) adipocytes. Furthermore, Nrf2 directly activated the Ucp1 promoter, and this required DNA regions located at -3.7 and -2.0 kb of the transcription start site. The CL316,243-induced Ucp1 expression in adipocytes and oxygen consumption in obese mice were partly compromised in the absence of Nrf2 expression. These data provide additional insight into the role of Nrf2 in β3-AR-mediated Ucp1 expression and energy expenditure, further highlighting the utility of Nrf2-mediated thermogenic stimulation as a therapeutic approach to diet-induced obesity.

• Journal of Sasang Constitutional Medicine
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• v.29 no.2
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• pp.154-173
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• 2017

Objectives This study was conducted to evaluate the effects of Yeoldahanso-tang on obesity in rats induced by high fat diet experimentally. Methods The experiment was conducted with rats divided into 5 groups. Rats were evaluated for change of weight, hematologic and serum biochemical parameters. Results Yeoldahanso-tang group showed significant reductions in FER, body weight, adipose tissue weight and size. The level of Creatinine, glucose, ALP, T-cholesterol, Triglyceride, LDL-cholesterol, Leptin and IGF-1 of Yeoldahanso-tang group was significantly lower than those in HFD-CTL group. The level of HDL-cholesterol, free fatty acid and Adiponectin in Yeoldahanso-tang group was significantly higher than those in HFD-CTL group. As compared with HFD-CTL group, AMPK-${\alpha}1$, UCP2 and adiponectin mRNA in liver of Yeoldahanso-tang group were significantly increased and AP2/FABP4, AMPK-${\alpha}2$ and PPAR-${\gamma}$ mRNA in liver of Yeoldahanso-tang group was significantly decreased. Conclusion These results suggest that Yeoldahanso-tang has inhibitory effects on obesity in high fat diet induced obese mice.

• Nutrition Research and Practice
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• v.15 no.4
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• pp.431-443
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• 2021

BACKGROUND/OBJECTIVES: Nobiletin (NOB), a citrus flavonoid, is reported to have beneficial effects on cardiovascular and metabolic health. However, there is limited research investigating the effect of long-term supplementation with low-dose NOB on high-cholesterol diet (HCD)-induced hypercholesterolemia and non-obese nonalcoholic fatty liver disease (NAFLD). Therefore, we investigated the influence of NOB on hypercholesterolemia and NAFLD in HCD-fed mice. SUBJECTS/METHODS: C57BL/6J mice were fed a normal diet (ND) or HCD (35 kcal% fat, 1.25% cholesterol, 0.5% cholic acid) with or without NOB (0.02%) for 20 weeks. RESULTS: HCD feeding markedly reduced the final body weight compared to ND feeding, with no apparent energy intake differences. NOB supplementation suppressed HCD-induced weight loss without altering energy intake. Moreover, NOB significantly decreased the total cholesterol (TC) levels and the low-density lipoprotein (LDL)/very-LDL-cholesterol to TC ratio, and increased the high-density lipoprotein-cholesterol/TC ratio in plasma, compared to those for HCD feeding alone. The plasma levels of inflammatory and atherosclerosis markers (C-reactive protein, oxidized LDL, interleukin [IL]-1β, IL-6, and plasminogen activator inhibitor-1) were significantly lower, whereas those of anti-atherogenic adiponectin and paraoxonase were higher in the NOB-supplemented group than in the HCD control group. Furthermore, NOB significantly decreased liver weight, hepatic cholesterol and triglyceride contents, and lipid droplet accumulation by inhibiting messenger RNA expression of hepatic genes and activity levels of cholesterol synthesis-, esterification-, and fatty acid synthesis-associated enzymes, concomitantly enhancing fatty acid oxidation-related gene expression and enzyme activities. Dietary NOB supplementation may protect against hypercholesterolemia and NAFLD via regulation of hepatic lipid metabolism in HCD-fed mice; these effects are associated with the amelioration of inflammation and reductions in the levels of atherosclerosis-associated cardiovascular markers. CONCLUSIONS: The present study suggests that NOB may serve as a potential therapeutic agent for the treatment of HCD-induced hypercholesterolemia and NAFLD.