• Asian-Australasian Journal of Animal Sciences
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• 제28권8호
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• pp.1187-1193
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• 2015

This study determined the effects of dietary restriction on growth and the expression of lipid metabolism and growth hormone signaling genes in the longissimus dorsi muscle (LM) of Korean cattle. Thirty-one Korean cattle steers (average age 10.5 months) were allocated to normal (N; n = 16) or dietary restriction (DR; n = 15) groups. The feeding trial consisted of two stages: for the 8-month growing period, the DR group was fed 80% of the food intake of the normal diet, and for the 6-month growth-finishing period, the DR group was fed a DR total mixed ration with 78.4% of the crude protein and 64% of the net energy for gain of the normal diet. The LM was biopsied 5 months (period 1 [P1] at 15.5 months of age) and 14 months (period 2 [P2] at 24.5 months of age) after the start of feeding. The mRNA levels were determined using real-time polymerase chain reaction. Body weight, daily feed intake, average daily gain, and feed efficiency were lower in the DR group compared with the normal group at both P1 and P2. At P1, the lipogenic fatty acid synthase (FASN) mRNA levels were lower (p<0.05) in the DR group compared with the normal group. The DR group tended (p = 0.06) to have higher of levels of growth hormone receptor (GHR) mRNA than the normal group. At P2, the DR group tended to have lower (p = 0.06) androgen receptor (AR) mRNA levels than the normal group. In conclusion, our results demonstrate that dietary restriction partially decreases the transcription of lipogenic FASN and growth hormone signaling AR genes, but increases transcription of the GHR gene. These changes in gene transcription might affect body fat accumulation and the growth of the animals.

• 동의생리병리학회지
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• 제27권6호
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• pp.802-808
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• 2013

Here we tried to uncover the potential anti-lipogenic effect and the underlying mechanism of Phaseolus angularis seed in a cellular model of nonalcoholic fatty liver disease (NAFLD) induced in HepG2 cells. Ethanol extract of Phaseolus angularis seed (JSD) was prepared. HepG2 cells were incubated in palmitate containing media to induce intracellular lipid accumulation, and co-treated with JSD for 16 hrs before examine intracellular lipid content. In control group, the cells were not co-treated with JSD. We measured the effects of JSD on liver X receptor ${\alpha}$ ($LXR{\alpha}$) and sterol regulatory element-binding transcription factor-1c (SREBP-1c) expression, transcription level of lipogenic genes, including acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), stearoyl-CoA desaturase-1 (SCD-1), and AMP-activated protein kinase (AMPK) activation in HepG2 cells. JSD markedly reduced palmitate-induced intracellular lipid accumulation in HepG2 cells. JSD suppressed $LXR{\alpha}$/SREBP-1c expression, and SREBP-1c mediated induction of ACC, FAS, and SCD-1. Furthermore, JSD activated AMPK, which plays a major role in the control of hepatic lipid metabolism. Taken together, it is suggested that JSD has a potential to alleviate hepatic steatosis, at least in part, by suppressing $LXR{\alpha}$/SREBP-1c mediated induction of lipogenic genes. In addtion, the anti-lipogenic potential may be associated with activation of AMPK. Therefore, the Phaseolus angularis seed could be applied as a potential therapeutics for NAFLD with additional clinical studies.

• Nutrition Research and Practice
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• 제14권6호
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• pp.568-579
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• 2020

BACKGROUD/OBJECTIVES: Hepatic steatosis is the most common liver disorder, particularly in postmenopausal women. This study investigated the protective effects of standardized rice bran extract (RBS) on ovariectomized (OVX)-induced hepatic steatosis in rats. MATERIALS/METHODS: HepG2 cells were incubated with 200 µM oleic acid to induce lipid accumulation with or without RBS and γ-oryzanol. OVX rats were separated into three groups and fed a normal diet (ND) or the ND containing 17β-estradiol (E2; 10 ㎍/kg) and RBS (500 mg/kg) for 16 weeks. RESULTS: RBS supplementation improved serum triglyceride and free fatty acid levels in OVX rats. Histological analysis showed that RBS significantly attenuated hepatic fat accumulation and decreased hepatic lipid, total cholesterol, and triglyceride levels. Additionally, RBS suppressed the estrogen deficiency-induced upregulation of lipogenic genes, such as sterol regulatory element-binding protein 1 (SREBP1), acetyl-CoA carboxylase 1, fatty acid synthase, glycerol-3-phosphate acyltransferase, and stearoyl-CoA desaturase 1. CONCLUSIONS: RBS and γ-oryzanol effectively reduced lipid accumulation in a HepG2 cell hepatic steatosis model. RBS improves OVX-induced hepatic steatosis by regulating the SREBP1-mediated activation of lipogenic genes, suggesting the benefits of RBS in preventing fatty liver in postmenopausal women.

• Natural Product Sciences
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• 제26권3호
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• pp.230-235
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• 2020

A pregnane steroid, 3α-hydroxy-pregn-7-ene-6,20-dione (1), was isolated from a Hydractinia-associated Cladosporium sphaerospermum SW67 by repetitive column chromatographic separation and high-performance liquid chromatography (HPLC) purification. The planar structure of 1 was elucidated from the analysis of the spectroscopic data (1D and 2D NMR spectra) and LC-MS data. The absolute configuration of 1 was determined by interpretation of ROESY spectrum of 1, together with the comparison of reported spectroscopic values in previous studies. To the best of our knowledge, this is the first report of the identification of the pregnane scaffold from C. sphaerospermum, a natural source. Compound 1 was evaluated for its effects on lipid metabolism and adipogenesis during adipocyte maturation and showed that compound 1 substantially inhibited lipid accumulation compared to the control. Consistently, the expression of the adipocyte marker gene (Adipsin) was reduced upon incubation with 1. Further, we evaluated the effects of 1 on lipid metabolism by measuring the transcription of lipolytic and lipogenic genes. The expression of the lipolytic gene ATGL was significantly elevated upon exposure to 1 during adipogenesis, whereas the expression of lipogenic genes FASN and SREBP1 was significantly reduced upon treatment with 1. Thus, our findings provide experimental evidence that the steroid derived from Hydractinia-associated C. sphaerospermum SW67 is a potential therapeutic agent for obesity.

• The Korean Journal of Physiology and Pharmacology
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• 제22권1호
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• pp.23-33
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• 2018

Cushing's syndrome (CS) is a collection of symptoms caused by prolonged exposure to excess cortisol. Chronically elevated glucocorticoid (GC) levels contribute to hepatic steatosis. We hypothesized that histone deacetylase inhibitors (HDACi) could attenuate hepatic steatosis through glucocorticoid receptor (GR) acetylation in experimental CS. To induce CS, we administered adrenocorticotropic hormone (ACTH; 40 ng/kg/day) to Sprague-Dawley rats by subcutaneous infusion with osmotic mini-pumps. We administered the HDACi, sodium valproate (VPA; 0.71% w/v), in the drinking water. Treatment with the HDACi decreased steatosis and the expression of lipogenic genes in the livers of CS rats. The enrichment of GR at the promoters of the lipogenic genes, such as acetyl-CoA carboxylase (Acc), fatty acid synthase (Fasn), and sterol regulatory element binding protein 1c (Srebp1c), was markedly decreased by VPA. Pan-HDACi and an HDAC class I-specific inhibitor, but not an HDAC class II a-specific inhibitor, attenuated dexamethasone (DEX)-induced lipogenesis in HepG2 cells. The transcriptional activity of Fasn was decreased by pretreatment with VPA. In addition, pretreatment with VPA decreased DEX-induced binding of GR to the glucocorticoid response element (GRE). Treatment with VPA increased the acetylation of GR in ACTH-infused rats and DEX-induced HepG2 cells. Taken together, these results indicate that HDAC inhibition attenuates hepatic steatosis through GR acetylation in experimental CS.

• BMB Reports
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• 제54권2호
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• pp.106-111
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• 2021

Hemistepsin A (HsA) is a guaianolide sesquiterpene lactone that inhibits hepatitis and liver fibrosis. We evaluated the effects of HsA on liver X receptor (LXR)-mediated hepatic lipogenesis in vitro and in vivo. Up to 10 μM, HsA did not affect the viability of HepG2 and Huh7 cells. Pretreatment with 5-10 μM HsA significantly decreased the luciferase activity of the LXR response element, which was transactivated by T0901317, GW 3965, and LXRα/retinoid X receptor α overexpression. In addition, it significantly inhibited the mRNA expression of LXRα in HepG2 and Huh7 cells. It also suppressed the expression of sterol regulatory element-binding protein-1c and lipogenic genes and reduced the triglyceride accumulation triggered by T0901317. Intraperitoneal injection of HsA (5 and 10 mg/kg) in mice significantly alleviated the T0901317-mediated increases in hepatocyte diameter and the percentage of regions in hepatic parenchyma occupied by lipid droplets. Furthermore, HsA significantly attenuated hepatic triglyceride accumulation by restoring the impaired expression of LXRα-dependent lipogenic genes caused by T0901317. Therefore, based on its inhibition of the LXRα-dependent signaling pathway, HsA has prophylactic potential for steatosis.

• 한국자원식물학회:학술대회논문집
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• 한국자원식물학회 2023년도 임시총회 및 춘계학술대회
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• pp.55-55
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• 2023

With the COVID-19 pandemic, there is increasing interest in anti-obesity strategies. According to the National Statistical Office, the obesity rate in Korea was 38.3% in 2020 and 37.1% in 2021. Obesity is a risk factor for several severe diseases, including stroke, heart disease, type 2 diabetes, and certain types of cancer. Pinus rigida × Pinus taeda is a hybrid of Pinus rigida Mill and Pinus taeda Linn, and its cones are considered a by-product. Although previous studies have investigated their pharmacological effects on antioxidant activity and protection against oxidative DNA damage, few researchers have explored their potential as functional natural materials. Therefore, we evaluated the anti-obesity effects of the cone of ethyl acetate fraction of P. rigida × P. taeda (ERT), specifically its ability to inhibit lipid accumulation. Our analysis showed that ERT contains phytochemicals (catechin and caffeic acid) which are known to improve immune function and inhibit cell damage. ERT inhibited lipid droplet accumulation at the cellular levels through Oil Red O staining. Furthermore, ERT suppressed the expression of adipogenic transcription factors (PPARγ and CEBP/α) as well as downstream lipogenic target genes (FAS and SREBP-1) thereby inhibiting adipogenesis. ERT also down-regulated key adipogenic markers, including aP2α, while inducing the phosphorylation of AMPK. It has been reported that PPARγ and CEBP/α are expressed in the early stages of adipose differentiation, while SREBP-1 is expressed in the late stage. Therefore, our findings suggest that ERT activates AMPK signaling pathways, which inhibits adipogenic transcription factors (PPARγ, C/EBPα, and SREBP1) and lipogenic genes (FAS and aP2α), thereby blocking lipid accumulation and preventing obesity and related disorders. ERT showed potential as a new resource for developing a functional material for anti-obesity agents.

• 한국가금학회지
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• 제36권4호
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• pp.301-309
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• 2009

본 연구는 육계에서 사료의 제한 급이 조건과 생체 내 지방 합성 및 근육 발달 관련 유전자들의 발현 양상을 비교 분석하기 위해여 실시하였다. 본 시험은 육계 Ross 종을 3처리 5반복 반복당 4수씩 완전 임의 배치하였으며, 7일령에 에너지제한 15%(ER85)와 30%(ER70)으로 하여 1주일간 제한 사양을 실시하였다. 제한 급이 이후 시험 종료까지(35일령)는 자유 급이를 실시하였다. 대조구는 전 사양 기간 동안 자유급이를 실시하였다. 에너지를 8일령부터 1주일간 제한 급이한 결과 대조구에 비하여 11.0%(ER85)와 30.8%(ER70) 각각 체성장이 낮게 나타났다. 제한 사양 후 3주간의 자유 급이 결과 ER85는 대조구와 같이 체성장을 이루어 보상 성장이 유도되었으나, ER70의 경우 대조구의 체성장보다 약 7.3% 낮게 나타나 보상 성장이 충분히 이루어지지 않았다. 제한 사양 후 콜레스테롤의 함량은 대조구에 비하여 40.6%(ER85)와 38.1%(ER70) 감소하였으나(P<0.05), 처리구간에는 유의적 차이를 나타내지 않았다. 중성지방 또한 대조구와 비교하여 64.5%(ER85), 49.5%(ER70) 각각감소하였다. 혈중포도당은 지방 성분들과 같은 경향으로 대조구에 비하여 34.5%(ER85), 27.7%(ER70) 각각 낮은 수준을 보였다. 보상 성장의 결과 혈중 콜레스테롤의 함량은 제한 사양 직후 대조구보다 낮은 수준에서 대조구와 같은 수준을 보였다. 혈중 중성지방은 대조구와 비교하여 처리구에서 102.3%(ER85)와 72.1%(ER70)의 높은 함량을 보여주어 제한 사양 직후와 상반된 결과를 보여 주었다. 혈중 포도당의 경우 ER70 처리구에서 비교적 높은 혈중 함량을 보였으며, 대조구와 ER85 그리고 처리구 간에는 유의적 차이를 보이지 않았다. 제한 사양 직후 FAS와 SREBP와 PPARr의 발현 양상은 ER70구에서 이들 유전자들의 발현이 감소하였을 뿐 대조구와 ER85구에서는 서로간의 차이를 볼 수 없었다. 제한 사양 후 14일령에 근육관련 유전자의 발현 양상은 대조구에 비해 모든 처리구에서 발현율이 낮게 나타났다. 보상 성장 후 ER85 처리군에서 Myogenin은 대조구와 ER70에 비하여 높은 발현을 보였다. 이상의 결과로부터 육계에서 보상 성장 및 근육 발달 관련 유전자들의 발현 양상을 고려할 때, 에너지 제한 15%(ER85) 수준이 적절한 제한 급이 방법으로 사료된다.

• 대한한방내과학회지
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• 제35권2호
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• pp.175-183
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• 2014

Objectives : We tried to uncover the anti-lipogenic effect and underlying mechanism of Laminaria japonica on an experimental cellular model of non-alcoholic fatty liver disease. Methods : Ethanol extract of Laminaria japonica (LJ) was prepared. Intracellular lipid content of palmitate-treated HepG2 cells was evaluated with or without LJ treatment. We measured the effects of LJ on liver X receptor ${\alpha}$ ($LXR{\alpha}$) and sterol regulatory element-binding transcription factor-1c (SREBP-1c) expression, transcription level of lipogenic genes, including acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), stearoyl-CoA desaturase-1 (SCD-1), and nuclear factor erythroid 2-related factor 2 (Nrf2) activation in HepG2 cells. Results : LJ markedly attenuated palmitate-induced intracellular lipid accumulation in HepG2 cells. LJ suppressed $LXR{\alpha}$-dependent SREBP-1c activation, and SREBP-1c mediated induction of ACC, FAS, and SCD-1. Furthermore, LJ activated Nrf2, which plays an important cytoprotective role in non-alcoholic fatty liver disease. Conclusions : Our study suggests that LJ has the potential to alleviate hepatic lipid accumulation, and this effect was mediated by inhibiting the $LXR{\alpha}$-SREBP-1c pathway that leads to hepatic steatosis. In addition, the anti-lipogenic potential may, at least in part, be associated with activation of Nrf2.

• 약학회지
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• 제53권5호
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• pp.286-292
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• 2009

In this study, we investigated the anti-obese activity of HPJ extract in C57BL/6J mice. The C57BL/6J mice were randomly divided into five groups: normal control group (Con), high fat diet control group (HFD), treatment groups with HPJ at 125 mg/kg (HPJ125), 250 mg/kg (HPJ250), or 500 mg/kg (HPJ500). To induce an obesity, mice were fed by a high fat diet for 6 weeks, and mice were administered with HPJ extract once a day for 8 weeks. At the end of treatment, we examined the effect of HPJ extract on body weight, plasma lipid, and lipogenic enzymes. HPJ extract was found to lower whole body and epididymal adipose tissue weights and lowered plasma levels of glucose, insulin, triglyceride (TG), total cholesterol (TC), non-esterified fatty acid (NEFA) and leptin, compared to those in HFD group. Histological analyses of the liver and fat tissues of mice treated with HPJ extract revealed significantly decreased number of lipid droplets and decreased size of adipocytes compared to the HFD group. In addition, HPJ extract preserved the morphological integrity of pancreatic islets. To elucidate an action mechanism of HPJ extract, Western blot and RT-PCR were performed using epididymal adipose tissues. HPJ extract up-regulated the levels of phosphorylated adenosine monophosphate-activated protein kinase (AMPK) and its substrate, acetyl-CoA carboxylasse (ACC). HPJ extract also attenuated lipogenic gene expressions of sterol regulatory element-binding protein $1{\alpha}$ (SREBP$1{\alpha}$), fatty acid synthase (FAS), sterol-CoA desaturase 1 (SCD1) and glycerol-3-phosphate acyltransferase (GPAT) in dose-dependent manners. In contrast, expressions of lipolytic genes such as peroxisome proliferator-activated receptor-$\alpha$ (PPAR-${\alpha}$) and CD36, and fatty acid $\beta$-oxidation gene, carnitine palmitoyltransferase-1 (CPT-1) were increased. These results suggest that HPJ extract ameliorates obesity through inhibiting synthesis of lipogenic enzymes as well as stimulating fatty acid oxidation resulting from activation of AMPK, and HPJ extract could be developed as a potential therapeutic agent for obese patients.