• Molecules and Cells
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• 제39권11호
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• pp.797-806
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• 2016

Lipogenesis is under the concerted action of ChREBP, SREBP-1c and other transcription factors in response to glucose and insulin. The isolated porcine preadipocytes were differentiated into mature adipocytes to investigate the roles and interrelation of these transcription factors in the context of glucose- and insulin-induced lipogenesis in pigs. In ChREBP-silenced adipocytes, glucose-induced lipogenesis decreased by ~70%, however insulin-induced lipogenesis was unaffected. Moreover, insulin had no effect on ChREBP expression of unperturbed adipocytes irrespective of glucose concentration, suggesting ChREBP mediate glucose-induced lipogenesis. Insulin stimulated SREBP-1c expression and when SREBP-1c activation was blocked, and the insulin-induced lipogenesis decreased by ~55%, suggesting SREBP-1c is a key transcription factor mediating insulin-induced lipogenesis. $LXR{\alpha}$ activation promoted lipogenesis and lipogenic genes expression. In ChREBP-silenced or SREBP-1c activation blocked adipocytes, $LXR{\alpha}$ activation facilitated lipogenesis and SREBP-1c expression, but had no effect on ChREBP expression. Therefore, $LXR{\alpha}$ might mediate lipogenesis via SREBP-1c rather than ChREBP. When ChREBP expression was silenced and SREBP-1c activation blocked simultaneously, glucose and insulin were still able to stimulated lipogenesis and lipogenic genes expression, and $LXR{\alpha}$ activation enhanced these effects, suggesting $LXR{\alpha}$ mediated directly glucose- and insulin-induced lipogenesis. In summary, glucose and insulin stimulated lipogenesis through both dissimilar and identical regulation pathway in porcine adipocytes.

• Preventive Nutrition and Food Science
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• 제3권4호
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• pp.362-367
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• 1998

Thyroid hormone(T3) stimulates hepatic lipogenesis by increasing expression of genes, indluding acetyl-CoA carboxylase and fatty acid synthase. S14 protein, which is thougth to be involved in lipid metabolism , appears to respond in parallel . Effect of T3 on lipogenesis in white and brown adipose tissue are less clear, and may be complicated by indirect effects of the hormone. We developed an adipocytes system where the indirect effects of thyroid hormone are abolished and direct effects of T3 on lipogenesis could be tested. Fat accumulation was mesured by Oil-Red O staining. Insulin clearly enhanced fat accumulation by 2-fold . Isobutylemethylxanthie(IBMX) apeared to inhibit insulin -stimulated fat accumulation. Dexamethasone increased insulin-stimulatedfat accumulation about 1.3-fold. confluent adipocytes were cultured in serum-free medium or medium containing 10% fetal calf serum or 10% fetal calf serum stripped of thyroid hormone and lipogenesis, assessed by the incorporation of 3H2O , was measured. Medium without serum or supplemented with T3-depleted serum did not amplify the stimulatory effect of T3 on lipogenesis compared to medium containing 10% fetal calf seru. Dexamethasone alone led to a decrease inlopogenesis of about 50 % in white adipocytes and 25% in brown adipocytes. However, dexamethasone amplified the lipogenic respnse to T3 by about 30% in whit eadipocytes and 60% in brown adipocytes. T3(1$\mu$M) stimulated lipogenesis and acetyl-CoA carboxylase and fatty acid syntase mRNA levels up to 2 -fold in both types of adipocytes. It seems that these adipocytes systems are as useful model to study the effects of hormones on lipogenic gene expression as well as lipogenesis.

• 생명과학회지
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• 제32권4호
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• pp.318-324
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• 2022

PPARγ와 C/EBPα는 adipose tissue 발생에 필요한 핵심 adipogenic TFs이다. 두 TFs는 adipose tissue의 배아 발생에 있어 초기 adipogenesis와 adipocytes 유전자 발현을 조절한다. Adipose expansion은 adipose tissue가 태어난 뒤에도 계속 팽창이 지속되는 것을 말한다. 이러한 adipose expansion은 후기 adipogenesis의 과정인 lipogenesis가 요구된다. 특히 간과 adipose tissue은 탄수화물이 기본적으로 fatty acids으로 전환되는 de novo lipogenesis (DNL)의 주요 장기이다. Fatty acids는 이어서 glycerol-3-phosphate에 에스테르화되어 adipocytes의 lipid droplets 생성을 위해 triglycerides로 전환된다. 간의 DNL이 활발하게 연구가 된 반면, in vivo에서 adipocytes의 DNL은 아직 잘 알려져 있지 않다. 그러므로, adipose expansion과 DNL에 대한 이해는 비만, 2형 당뇨 그리고 대사성 질환을 위한 치료제 개발에 도움을 줄 수 있다. Adipocytes에서 DNL 유전자 발현은 ChREBP나 SREBP1a와 같은 lipogenic TFs 뿐 아니라, lipogenesis coactivator에 의해 전사 수준에서 조절된다. 최근 in vivo 연구에 의해 lipogenesis 유전자 발현과 adipose expansion의 새로운 측면이 밝혀졌다. 향후 구체적인 분자기전 연구는 어떻게 영양분이 DNL과 adipose expansion을 조절하는 지를 규명해 줄 것이다. 본 리뷰논문은 전사조절 관점에서 adipocytes와 adipose expansion에 있어 DNL에 대한 최신 연구결과를 요약정리 할 것이다.

• Asian-Australasian Journal of Animal Sciences
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• 제13권9호
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• pp.1285-1289
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• 2000

This study investigated the lipogenesis capacity of hepatocytes and lipolysis rate of adipocytes of broilers as affected by different fatty acids (trial one) and different linoleic acid (C18:2) levels (trial two). Twenty 6-wk old broilers were used; their hepatocytes and adipocytes were isolated for the in vitro study. In trial one, four treatments were tested. The control group in which no fatty acid was added, and the test groups to which were added $300{\mu}M$ of C16:0, C18:1 and C18:2, respectively. For trial two, different levels (0, $300{\mu}M$ and 1 mM) of C18:2 combined to fatty acid-free bovine serum albumin (BSA) were added to the medium. According to results of trial one, added fatty acids significantly reduced the incorporation by hepatocytes of [U,$^{14}C$]glucose into total lipid (p<0.05); the lipogenesis capacity in C18:2 group was the lowest. Although a similar pattern was found with [l,$^{14}C$]acetate, the groups only slightly differed in terms of lipogenesis capacity (p=0.11). In addition, the C18:2 group had a significantly (p<0.05) greater lipolysis rate than the C16:0 and control groups. Results of trial two indicated that C18:2 significantly (p<0.05) reduced lipogenesis capacity both for [U,$^{14}C$]glucose and [l,$^{14}C$]acetate, and markedly stimulated the lipolysis rate (p<0.05), displaying a dose response. Results presented herein demonstrate that C18:2 can reduce lipogenesis capacity and stimulate the lipolysis rate in broilers.

• Korean Journal of Acupuncture
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• 제31권4호
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• pp.168-178
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• 2014

Objectives : Mahuang-Chuanwu(Mahwang-Cheonoh) Pharmacopuncture(MCP) has been used to treat obesity in Clinical Korean Medicine. MCP solution(MCPS) is also expected to have strong anti-obesity activities. However, little is known about the mechanisms of its inhibitory effects on adipocyte differentiation and lipogenesis. Methods : In the present study, we examined the effects of MCPS on differentiation and lipogenesis of 3T3-L1 adipocytes. To elucidate the mechanism of the effects of MCPS on lowering lipid content in 3T3-L1 adipocytes, we examined whether MCPS modulates the expressions of transcription factors to induce lipogenesis and adipogenic genes related to regulate the accumulation of lipids. Results : Our results showed that MCPS significantly inhibited differentiation and lipogenesis of 3T3-L1 adipocytes in a dose-dependent manner. MCPS suppressed the mRNA expressions of cytidine-cytidine-adenosine-adenosine-thymidine(CCAAT)/enhancer binding proteins ${\alpha}$($C/EBP{\alpha}$), C/EBP ${\beta}$, $C/EBP{\delta}$, and peroxisome proliferator-activated receptor ${\gamma}$($PPAR{\gamma}$) genes related to the induction of adipose differentiation. MCPS inhibited the mRNA expressions of adipose-specific aP2, adipsin, lipoprotein lipase(LPL), CD36, TGF-${\beta}$, and leptin genes related to the fat formation. MCPS downregulated the mRNA expressions of liver X receptor(LXR) ${\alpha}$ and fatty acid synthase(FAS) genes related to the induction of lipogenesis. In addition, MCPS reduced the production of adipocyte-induced pro-inflammatory cytokines. Conclusions : MCPS could regulate the accumulation of lipids and expression of adipogenic genes via inhibition of transcript factors related to induction of adipose differentiation.

• Asian-Australasian Journal of Animal Sciences
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• 제20권9호
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• pp.1417-1423
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• 2007

The present study was conducted to investigate the supplementation effects of $C_{18:2}$ rich-soybean oil or $C_{18:3}$ rich-perilla oil (7% of total diet, DM basis) for 12 weeks on plasma metabolites, fatty acid profile, in vitro lipogenesis, and activities of LPL and FAS in adipose tissue of sheep. The treatments were basal diet (Control), $C_{18:2}$ rich-soybean oil supplemented diet (SO-D) and $C_{18:3}$ rich-perilla oil supplemented diet (PO-D). All the sheep were fed the diets consisting of roughage to concentrate in the ratio of 40:60 (DM basis). Oil supplemented diets (SO-D and PO-D) slightly increased contents of triglyceride (TG) and total cholesterol (TC), proportions of both cis-9 trans-11 and trans-10 cis-12 CLA and TVA, but lowered (p<0.01) those of $C_{18:0}$ compared to the control diet. No differences were observed in the contents of TG and TC and proportions of fatty acids in plasma between supplemented oils. Oil supplemented diets slightly increased the proportions of cis-9 trans-11 and trans-10 cis-12 types of CLA in subcutaneous adipose tissue of sheep compared to the control diet. The rate of lipogenesis with acetate was higher (p<0.01) for intermuscular- and subcutaneous adipose tissues than that for intramuscular adipose tissue, while that with glucose did not differ among fat locations in sheep fed SO-D. No differences were observed in the rate of lipogenesis between substrates in all fat locations. The rates of lipogenesis with glucose increased only in the intermuscular- (p<0.01) and subcutaneous adipose tissue (p<0.005) compared to those with acetate. The rates of lipogenesis with acetate were the highest in the intermuscular and intramuscular adipose tissue of the sheep fed PO-D. Oil supplemented diets slightly increased the rate of lipogenesis with glucose for all fat locations. Supplementation of oils to the diet numerically increased the fatty acid synthase activity but did not affect the lipoprotein lipase activity in subcutaneous adipose tissue.

• Molecules and Cells
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• 제44권2호
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• pp.116-125
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• 2021

Cardiovascular diseases (CVDs) are the most common cause of death in patients with nonalcoholic fatty liver disease (NAFLD) and dyslipidemia is considered at least partially responsible for the increased CVD risk in NAFLD patients. The aim of the present study is to understand how hepatic de novo lipogenesis influences hepatic cholesterol content as well as its effects on the plasma lipid levels. Hepatic lipogenesis was induced in mice by feeding a fat-free/high-sucrose (FF/HS) diet and the metabolic pathways associated with cholesterol were then analyzed. Both liver triglyceride and cholesterol contents were significantly increased in mice fed an FF/HS diet. Activation of fatty acid synthesis driven by the activation of sterol regulatory element binding protein (SREBP)-1c resulted in the increased liver triglycerides. The augmented cholesterol content in the liver could not be explained by an increased cholesterol synthesis, which was decreased by the FF/HS diet. HMG-CoA reductase protein level was decreased in mice fed an FF/HS diet. We found that the liver retained more cholesterol through a reduced excretion of bile acids, a reduced fecal cholesterol excretion, and an increased cholesterol uptake from plasma lipoproteins. Very low-density lipoproteintriglyceride and -cholesterol secretion were increased in mice fed an FF/HS diet, which led to hypertriglyceridemia and hypercholesterolemia in Ldlr-/- mice, a model that exhibits a more human like lipoprotein profile. These findings suggest that dietary cholesterol intake and cholesterol synthesis rates cannot only explain the hypercholesterolemia associated with NAFLD, and that the control of fatty acid synthesis should be considered for the management of dyslipidemia.

• Journal of Animal Science and Technology
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• 제52권5호
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• pp.383-388
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• 2010

In vivo 실험에 의해서 지방축적을 억제할 수 있는 물질을 찾아내는 것은 시간과 비용이 많이 든다. 본 연구는 돼지 지방조직을 이용한 in vitro system을 이용해서 한국의 약용식물 중에서 지방축적 억제 작용을 가지는 것을 조사하고자 수행하였다. 총 183종의 약용식물을 이용하여 이들이 돼지 지방조직의 지방합성과 지방전구세포의 분화에 미치는 작용을 조사하였다. 에탄올 추출물은 72종, 물 추출물은 111종, 이 중에서 65종은 물과 에탄올 모두 이용해서 추출하였다. 돼지 지방조직의 지방합성은 13종류의 약용식물이 영향을 미쳤는데, 그 중 11종은 대조구에 비하여 지방합성을 40% 이상 억제하였고, 4종은 지방합성을 70% 이상 억제하였다. 가장 강력한 지방합성 억제작용을 나타낸 것은 붓꽃과와 고삼(에탄올 추출) 그리고 좁쌀풀(물과 에탄올 추출)이었다. 그러나 소목과 황백은 지방합성을 촉진하였다. 돼지 지방전구세포의 분화에 미치는 결과는 총 28종의 약용식물이 돼지 지방전구세포의 분화에 영향을 미쳤는데, 이 중 16종의 약용식물은 증가시켰고, 12종은 억제시켰다. 목단피와 강활(에탄올 추출) 그리고 당귀, 목향 및 신이(물 추출)는 지방세포의 분화를 두 배 정도 증가시켰다. 10종의 약용식물 즉 감초, 형개 및 구월나무(에탄올 추출) 그리고 비름과, 천문동, 백출, 유자나무, 향부자, 구엽초 및 목단피(물 추출)은 지방세포의 분화를 35% 이상 억제시켰다. 구월나무(에탄올 추출)만이 지방합성뿐만 아니라 세포분화도 억제하였다. 본 연구 결과는 약용식물로부터 가축과 사람의 지방축적 억제효능 후보물질을 발굴하기 위한 기초자료로 활용할 수 있을 것으로 여겨진다.

• Journal of Microbiology and Biotechnology
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• 제23권11호
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• pp.1569-1576
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• 2013

In mice, supplementation of t10,c12 conjugated linoleic acid (CLA) increases liver mass and hepatic steatosis via increasing uptake of fatty acids released from adipose tissues. However, the effects of t10,c12 CLA on hepatic lipid synthesis and the associated mechanisms are largely unknown. Thus, we tested the hypothesis that gut microbiota-producing t10,c12 CLA would induce de novo lipogenesis and triglyceride (TG) synthesis in HepG2 cells, promoting lipid accumulation. It was found that treatment with t10,c12 CLA ($100{\mu}M$) for 72 h increased neutral lipid accumulation via enhanced incorporation of acetate, palmitate, oleate, and 2-deoxyglucose into TG. Furthermore, treatment with t10,c12 CLA led to increased mRNA expression and protein levels of lipogenic genes including SREBP1, ACC1, FASN, ELOVL6, GPAT1, and DGAT1, presenting potential mechanisms by which CLA may increase lipid deposition. Most strikingly, t10,c12 CLA treatment for 3 h increased phosphorylation of mTOR, S6K, and S6. Taken together, gut microbiota-producing t10,c12 CLA activates hepatic de novo lipogenesis and TG synthesis through activation of the mTOR/SREBP1 pathway, with consequent lipid accumulation in HepG2 cells.

• The Korean Journal of Physiology and Pharmacology
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• 제28권3호
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• pp.219-227
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• 2024

Bladder cancer remains the 10th most common cancer worldwide. In recent years, metformin has been found to have potential anti-bladder cancer activity while high concentration of IC₅₀ at millimolar level is needed, which could not be reached by regular oral administration route. Thus, higher efficient agent is urgently demanded for clinically treating bladder cancer. Here, by conjugating artesunate to metformin, a novel artesunate-metformin dimer triazine derivative AM2 was designed and synthesized. The inhibitory effect of AM2 on bladder cancer cell line T24 and the mechanism underlying was determined. Anti-tumor activity of AM2 was assessed by MTT, cloning formation and wound healing assays. Decreasing effect of AM2 on lipogenesis was determined by oil red O staining. The protein expressions of Clusterin, SREBP1 and FASN in T24 cells were evaluated by Western blotting. The results show that AM2 significantly inhibited cell proliferation and migration at micromolar level, much higher than parental metformin. AM2 reduced lipogenesis and down-regulated the expressions of Clusterin, SREBP1 and FASN. These results suggest that AM2 inhibits the growth of bladder cancer cells T24 by inhibiting cellular lipogenesis associated with the Clusterin/SREBP1/FASN signaling pathway.