Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids <i>in vitro</i> and rat liver <i>in vivo</i>

Kim, Bu-Yeo,Kim, Minjeong,Jeong, Ji Seong,Jee, Sun-Ha,Park, Il-Hyun,Lee, Byung-Chul,Chung, Sun-Ku,Lim, Kyung-Min,Lee, Yun-Sil Elsevier 2019 Environmental research Vol.173 No.-

<P><B>Abstract</B></P> <P>Bisphenol A (BPA), a synthetic monomer commonly included in the daily products, has a structure similar to the estrogen receptor agonist. Therefore BPA has been anticipated to interfere with the hormone metabolisms and cause diverse pathological conditions. But the effects of BPA on the genetic landscapes of liver or hepatic cells have not been fully established. Gene expressional changes induced by low- or high-dose of BPA were evaluated in 3D cultured human hepatoma cells (HepG2 spheroids) <I>in vitro</I> at 0, 0.5, 5 and 200 μM and liver of rats exposed to BPA at 0, 0.5 and 250 mg/kg for 90 days <I>in vivo</I>. Functional enrichment analysis, pathway activity measurement and network analysis were performed using BPA-responsive genes. Treatment with BPA changed a lot of gene expressions in both HepG2 spheroids and rat livers depending on doses of BPA. Functional enrichment and pathway analysis show that lipid or steroid metabolism-related functions were altered by BPA in both HepG2 spheroids and livers of rats. Lipid metabolism-related functions altered by BPA formed a large cluster encompassing lipid biosynthesis, steroid metabolic process and cholesterol regulation process. It was also observed that distribution of pathway activities was correlated between HepG2 spheroids and rat livers at low-dose of BPA. Distance distribution in protein-protein interaction network also evidenced the closeness of BPA-responsive genes to metabolism pathways which include lipid metabolism. Collectively, we demonstrated that BPA greatly influenced overall gene expression and biological functions in both human hepatoma spheroids and rat liver, in which lipid- or steroid metabolism-associated genes were significantly altered by the exposure to BPA.</P> <P><B>Highlights</B></P> <P> <UL> <LI> BPA induced transcriptomic changes associated with lipid and sterol metabolism in HepG2 spheroids and rat liver. </LI> <LI> Functional enrichment, pathway, pathway activity and protein-protein interaction network analyses coherently support low dose effects of BPA on lipid metabolism. </LI> <LI> The effects on lipid metabolisms are well in line with human metabolomics and epidemiological studies. </LI> <LI> The altered lipid metabolism pathways by BPA were demonstrated in both human cells and animals. </LI> </UL> </P>

Effects of Skin Surface Lipids on Skin Health

Faqing Feng,Laiji Ma,Zhaohui Qu,Yinmao Dong,Fan Yi 한국피부과학연구원 2019 아시안뷰티화장품학술지 Vol.17 No.1

Skin surface lipids are composed of sebaceous glands secreting lipids and epidermal disintegration lipids. The main components include triglycerides, free fatty acids, wax esters, squalene, cholesterol and so on. Skin surface lipids adhere to the surface of the skin and rely on their physical, chemical and biological properties to be important for skin health. This article reviews the relevant literatures at home and abroad, briefly describes the effects of skin surface lipids on skin moisturization, anti-oxidation and maintenance of micro-ecology, and mainly introduces the oxidation/metabolism of squalene/free fatty acids, which is more affected by external harmful factors than other skin surface lipids. As well as, the effects on skin health of squalene oxidation products and triglyceride metabolites are introduced. Above all, the oxidation/metabolism of skin surface lipids and the role of their products are illustrated in order to reveal the relationship between skin surface lipids and skin health and to provide a theoretical reference for the research and development of cosmetics by regulating skin surface lipids. Keywords: Skin surface lipids, Squalene, Free fatty acids, Oxidation

비만인의 지방대사 활성화를 위한 운동의 역할

김기진 한국운동과학회 2003 운동과학 Vol.12 No.4

김기진. 비만인의 지방대사 활성화를 위한 운동의 역할 운동과학, 제12권 제4호, 553-574, 2003. 운동요법은 에너지소비량 증가 및 지방이용 등울 활성화시켜 비만처치의 가장 중요한 프로그램으로 간주되고 있다. 비만인의 지방대사 저하 현상은 근육 및 혈중의 유리지방산 함량 차이, 근육의 대사기능 저하, 호르몬과 교감신경계에 대한 감수성 저하 등이 주된 요인으로 작용한다. 특히, 비만인의 근육의 지방 대사기능 관련요인에는 유리지방산의 운반능력, β-산화 능력, 근섬유 구성상 특성, 모세혈관 밀도 및 혈류공급능력 등의 부정적인 특성이 포함된다. 아울러 지방대사에 영향을 미치는 요인으로 유전인자에 의한 영향이 널리 제시되고 있으며, 유전자 변이현상은 지방대사 저하와 함께 비만 처치프로그램 적용시 그 효과의 부진현상을 나타내는 주된 요인으로 간주되고 있다. 운동프로그램은 운동강도 및 운동형태의 적절성이 이루어질 경우 지방대사 억제현상을 보다 효과적으로 극복할 수 있으며, 운동강도는 최대산소섭취량기준 40-65%의 범위에서 개인차를 고려하여 적절하게 설정해야 한다. 운동수행시 고온 및 저온의 기온차이를 비롯한 환경적 특성을 고려한 부가적 효과의 가능성도 제시되고 있다. 선행연구를 종합하면, 체중감소에는 식이요법, 지방산좌에는 유산소운동, 제지방 체중을 유지하기 위해서는 저항운동 등이 주로 이용될 수 있으나, 지방대사 활성화 및 제지방 체중의 유지를 통한 보다 효과적인 체중감소를 위해서는 세가지 프로그램을 적절하게 병행하는 것이 가장 이상적이라고 할 수 있다. 그러나, 비만의 효과적인 처치를 위해서는 운동프로그램 적용시 에너지섭취 및 소비과정에서의 지방대사를 중심으로 한 복합적인 고려가 요구 된다. 아울러 비만처치 프로그램 적용시 유전적 특성에 의한 영향도 고려되어야 하며, 특히 분자생물학적 분석을 통한 지방대사 활성화를 위한 방안 모색이 이루어져 한다. Kim, K.J. The role of exercise on the activation of lipid metabolism in obese. Exercise Science, 12(4): 553-574, 2003. Exorcise program is an effective treatment of obesity by the increase of energy expenditure and fat availability. The differences of FFA concentration between blood and muscle, the decrease ol muscular metabolism, and the depressions of hormonal sensitivity and sympathetic nerve function have been shown the main factors on the decrease of lipid metabolism in obese. The determinant factors of muscular lipid metabolism have been suggested the FFA transport function, β-oxidative capacity, muscle liber composition, the capillary density and blood supply, and the functional capacities related to these factors depressed in obese. And the genetic factors have been considered to the additional main factors of lipid metabolism related to obesity in many previous studies. Especially, the gene mutation arised to the depression of lipid metabolism and the inhibition of effect of exorcise treatment on the weight control. When the exorcise program treated for the improvement of lipid metabolism In obese, the optimal intensity (40-65%VO₂max) and mode of exorcise seem to be important. And the consideration of environmental condition as cold and heat could be suggested for the effective exorcise program in the treatment of obesity. The most effective treatment of obesity is the combination method of the diet, aerobic exorcise, and resistance exorcise. More importantly than weight loss is the evidence that this combination program increases lipid metabolism and helps preserve FFM. Further research is required to the molecular biological analysis related to genetic factors and the activation of lipid metabolism.

Effects of lycopene on abdominal fat deposition, serum lipids levels and hepatic lipid metabolism-related enzymes in broiler chickens

Wan Xiaoli,Yang Zhengfeng,Ji Haoran,Li Ning,Yang Zhi,Xu Lei,Yang Haiming,Wang Zhiyue 아세아·태평양축산학회 2021 Animal Bioscience Vol.34 No.3

Objective: The present study was conducted to investigate the effects of lycopene on growth performance, abdominal fat deposition, serum lipids levels, activities of hepatic lipid metabolism related enzymes and genes expression in broiler chickens. Methods: A total of 256 healthy one-day-old male Arbor Acres broiler chicks were randomly divided into four groups with eight replicates of eight birds each. Birds were fed basal diet supplemented with 0 (control), 100, 200, and 400 mg/kg lycopene, respectively. Results: Dietary 100 mg/kg lycopene increased the body weight at 21 day of age compared to the control group (p<0.05). Compared to the basal diet, broilers fed diet with 100 mg/kg lycopene had decreased abdominal fat weight, and broilers fed diet with 100 and 200 mg/kg lycopene had decreased abdominal fat percentage (p<0.05). Compared to control, diets with 100, 200, and 400 mg/kg lycopene reduced the levels of total triglyceride and total cholesterol in serum, and diets with 100 and 200 mg/kg lycopene reduced the level of serum low density lipoprotein cholesterol (p<0.05). The activity of fatty acid synthase (FAS) in 400 mg/kg lycopene treated broilers and the activity of acetyl-CoA carboxylase (ACC) in 100, 200, and 400 mg/kg lycopene treated broilers were lower than those fed basal diet (p<0.05). Lycopene increased the mRNA abundance of adenosine monophosphate activated protein kinase α (AMPK-α), whereas decreased the mRNA abundance of sterol regulatory elementbinding protein 1, FAS, and ACC compared to the control group (p<0.05). Conclusion: Dietary lycopene supplementation can alleviate abdominal fat deposition and decrease serum lipids levels, possibly through activating the AMPK signaling pathway, thereby regulating lipid metabolism such as lipogenesis. Therefore, lycopene or lycopenerich plant materials might be added to poultry feed to regulate lipid metabolism. Objective: The present study was conducted to investigate the effects of lycopene on growth performance, abdominal fat deposition, serum lipids levels, activities of hepatic lipid metabolism related enzymes and genes expression in broiler chickens.Methods: A total of 256 healthy one-day-old male Arbor Acres broiler chicks were randomly divided into four groups with eight replicates of eight birds each. Birds were fed basal diet supplemented with 0 (control), 100, 200, and 400 mg/kg lycopene, respectively.Results: Dietary 100 mg/kg lycopene increased the body weight at 21 day of age compared to the control group (p<0.05). Compared to the basal diet, broilers fed diet with 100 mg/kg lycopene had decreased abdominal fat weight, and broilers fed diet with 100 and 200 mg/kg lycopene had decreased abdominal fat percentage (p<0.05). Compared to control, diets with 100, 200, and 400 mg/kg lycopene reduced the levels of total triglyceride and total cholesterol in serum, and diets with 100 and 200 mg/kg lycopene reduced the level of serum low density lipoprotein cholesterol (p<0.05). The activity of fatty acid synthase (FAS) in 400 mg/kg lycopene treated broilers and the activity of acetyl-CoA carboxylase (ACC) in 100, 200, and 400 mg/kg lycopene treated broilers were lower than those fed basal diet (p<0.05). Lycopene increased the mRNA abundance of adenosine monophosphate activated protein kinase α (AMPK-α), whereas decreased the mRNA abundance of sterol regulatory elementbinding protein 1, FAS, and ACC compared to the control group (p<0.05).Conclusion: Dietary lycopene supplementation can alleviate abdominal fat deposition and decrease serum lipids levels, possibly through activating the AMPK signaling pathway, thereby regulating lipid metabolism such as lipogenesis. Therefore, lycopene or lycopenerich plant materials might be added to poultry feed to regulate lipid metabolism.

Quantifications of Lipid Kinetics In Vivo Using Stable Isotope Tracer Methodology

김일영,박상희,장지웅,Robert R. Wolfe 한국지질동맥경화학회 2020 지질·동맥경화학회지 Vol.9 No.1

Like other bodily materials, lipids such as plasma triacylglycerol, cholesterols, and free fatty acids are in a dynamic state of constant turnover (i.e., synthesis, breakdown, oxidation, and/or conversion to other compounds) as essential processes for achieving dynamic homeostasis in the body. However, dysregulation of lipid turnover can lead to clinical conditions such as obesity, fatty liver disease, and dyslipidemia. Assessment of “snap-shot” information on lipid metabolism (e.g., tissue contents of lipids, abundance of mRNA and protein and/or signaling molecules) are often used in clinical and research settings, and can help to understand one's health and disease status. However, such “snapshots” do not provide critical information on dynamic nature of lipid metabolism, and therefore may miss “true” origin of the dysregulation implicated in related diseases. In this regard, stable isotope tracer methodology can provide the in vivo kinetic information of lipid metabolism. Combining with “static” information, knowledge of lipid kinetics can enable the acquisition of in depth understanding of lipid metabolism in relation to various health and disease status. This in turn facilitates the development of effective therapeutic approaches (e.g., exercise, nutrition, and/or drugs). In this review we will discuss 1) the importance of obtaining kinetic information for a better understanding of lipid metabolism, 2) basic principles of stable isotope tracer methodologies that enable exploration of “lipid kinetics” in vivo, and 3) quantification of some aspects of lipid kinetics in vivo with numerical examples.

Phenotypic Assessment of Lipid Droplets using Daphnia magna Model

Kojo Eghan,이상우,김우근 환경독성보건학회 2021 한국독성학회 심포지움 및 학술발표회 Vol.2021 No.5

Lipids storage, accumulation and metabolism in organisms can be altered by several factors including the environment, exogenous and endogenous compounds. Additional energy stores in the form of lipids gives living organisms a substantial metabolic benefit, nonetheless, an energy balance disorder could lead to lipid diseases and liver dysfunctions. For crustaceans, this tends to affect their overall growth and development. In Daphnia magna, growth, molting, and reproductive functions are regulated by the amount and fate of storage lipids. Tributyltin (TBT), one of the well-known toxic pollutants to be found in the aquatic environment, is a substance that resists degradation and is absorbed by organic materials such as bacteria and algae. In this study, we seek to develop a model that can be used to study the mechanisms involved in lipid metabolism associated with accumulation, uptake and regulation. With little know about the formation and metabolism of lipid droplets in Daphnia manga both physically and transcriptionally, we employed this in vivo model in our study. Daphnia magna individuals of 5 days old were exposed to TBT 0, 1.0 and 1.0 μg/L for 48 h. Then, Oil Red O and Nile red staining processes were carried out, stained individuals were observed under a stereo microscope and confocal microscope, respectively. The transcription of selected genes (rxr, cer2, hr96, magro, man, NPC1b & SM3) involved in fat metabolism was also analyzed using qPCR techniques. From our findings, microscopic Daphnia magna images from both Nile red and Oil red staining showed analogous patterns. At the transcription level, rxr, cer2 and SM3 had being significantly altered. The Daphnia magna successfully responded to our tests and significant effects were observed as expected. Our findings indicate that TBT facilitates the uptake and accumulation of lipids in Daphnia magna. Therefore, the Daphnia magna model presents an endless potential to tap into, and can be an alternative to test lipid metabolism altering chemicals. Nonetheless, further research needs to be done on lipid metabolism mechanobiology, to understand how cells respond to mechanical signals that causes a disruption in lipids production and use.

Targeting Lipid Metabolic Reprogramming as Anticancer Therapeutics

차지영,이호재 대한암예방학회 2016 Journal of cancer prevention Vol.21 No.4

Cancer cells rewire their metabolism to satisfy the demands of growth and survival, and this metabolic reprogramming has been recognized as an emerging hallmark of cancer. Lipid metabolism is pivotal in cellular process that converts nutrients into energy, building blocks for membrane biogenesis and the generation of signaling molecules. Accumulating evidence suggests that cancer cells show alterations in different aspects of lipid metabolism. The changes in lipid metabolism of cancer cells can affect numerous cellular processes, including cell growth, proliferation, differentiation, and survival. The potential dependence of cancer cells on the deregulated lipid metabolism suggests that enzymes and regulating factors involved in this process are promising targets for cancer treatment. In this review, we focus on the features associated with the lipid metabolic pathways in cancer, and highlight recent advances on the therapeutic targets of specific lipid metabolic enzymes or regulating factors and target-directed small molecules that can be potentially used as anticancer drugs.

3T3-L1 지방세포에 대한 와송 디클로로메탄 추출물의 지질 대사개선에 관한 연구

김수환,이형선 대한임상검사과학회 2019 대한임상검사과학회지(KJCLS) Vol.51 No.4

This study investigated the improved lipid metabolism effect of 3T3-L1 cells induced by adipocytes using the dichloromethane (DCM) fraction in the organic solvent extract of Wassong (Orostachys japonicus). To confirm the cell cytotoxicity, each of 6 fractions of organic solvent extracts (EtOH, Hexane, DCM, EtOAc, BuOH, and H2O) was examined using MTS assay. As a result, it was confirmed that the DCM extract was stable over the whole range of concentrations, and a DCM fraction was used to confirm the improved lipid metabolism effect. Lipid excretion was measured to confirm the change of lipid metabolism. 3T3-L1 cells induced by adipocytes were treated with DCM extract and stained with oil-red O to evaluate lipid accumulation. As a result, it was confirmed that the lipid efflux was significantly improved. In order to confirm the mechanism of lipid efflux, the mRNA expressions of ABCA1 and ABCG1, which are lipid transport proteins, were confirmed by real-time PCR. Therefore, the present study confirmed that the DCM extract from Orostachys japonicus has the effect of improving the lipid metabolism on 3T3-L1 adipocytes. In addition, the results of this study will be used as the basis for the development of functional foods using Orostachys japonicus and also for conducting research on the detailed mechanisms. 본 연구는 와송 유기용매 추출물중 DCM층을 이용하여 지방세포로 유도된 3T3-L1세포에 대한 지질대사 개선효과를 확인하는 연구이다. 세포독성을 확인하기 위하여 MTS-assay를 이용하여 6가지 분획의 와송 유기용매 추출물(EtOH, Hexane, DCM, EToAc, BuOH, H2O)에 대한 독성검사를 실시하여 세포에 대한 안정성을 확인하였다. 그 결과 DCM추출물이 전 농도에 걸쳐 안정성이 있음을 확인하고, 지질대사 개선효과를 확인하기 위하여 DCM층을 사용하였다. 우선 지질대사 개선효과를확인하기 위하여 지질 배출능을 측정하였다. 지방세포로 유도된 3T3-L1세포에 대하여 DCM추출물을 처리한 후 oil-red O 염색을 실시하여 지질 축적량을 평가한 결과 지질 배출능이 개선된 것을 확인할 수 있었다. 또한 지질 배출능 분석을 위하여 지질수송 단백질인 ABCA1, ABCG1의 mRNA발현을 real-time PCR로 확인한 결과 DCM추출물 처리 시 유의적인 발현 증가가나타났음을 확인 하였다. 따라서 본 연구를 통하여 와송 DCM추출물이 3T3-L1 지방세포에 대하여 지질대사 개선효과가 있음을 확인하였다.

건선에 효과적인 한약 처방 탐색 - 지질 대사를 중심으로

한창이,김준동,서광일,김규석,김윤범,Han, Chang-Yi,Kim, Jundong,Seo, Gwang-Yeel,Kim, Kyu-Seok,Kim, Yoon-Bum 대한한방안이비인후피부과학회 2021 한방안이비인후피부과학회지 Vol.34 No.3

Objectives : The purpose of this study is to investigate the possibility of using herbal medicine for the management of psoriasis focusing on lipid metabolism. Methods : We reviewed studies about pathophysiology, and medical treatment of psoriasis, the relationship between psoriasis and metabolic syndrome and lipid metabolism, and herbal medicine on Pubmed and Google scholar. Results : Psoriasis is a chronic multi-organ inflammatory disease not limited to skin, and steroids, immuno-suppressants, and biological agents are used. It is known that psoriasis and metabolic syndrome act as mutual risk factors, and lipid metabolism are involved in psoriasis. The effects of various single herbal preparations and complex herbal extract, decoction on improving lipid metabolism have been consistently reported, and there was an improvement of psoriatic skin lesions and improvement of blood lipid levels through herbal medicine. Conclusions : Herbal medicine research in psoriasis has focused on the anti-inflammatory effect and the suppression effect of certain immune mediators. However, considering that psoriasis is affected by lipid metabolism and side effects of Western medicines, the use of herbal medicines for the purpose of controlling lipid metabolism in psoriasis is useful in aspects of reducing side effects of concurrent Western medicine, improving the severity of psoriasis, and managing metabolic risk factors.

Hepatic microRNAome reveals potential microRNA-mRNA pairs association with lipid metabolism in pigs

Jingge Liu,Caibo Ning,Bo-jiang Li,Rongyang Li,Wang Jun Wu,Honglin Liu 아세아·태평양축산학회 2019 Animal Bioscience Vol.32 No.9

Objective: As one of the most important metabolic organs, the liver plays vital roles in modulating the lipid metabolism. This study was to compare miRNA expression profiles of the Large White liver between two different developmental periods and to identify candidate miRNAs for lipid metabolism. Methods: Eight liver samples were collected from White Large of 70-day fetus (P70) and of 70-day piglets (D70) (with 4 biological repeats at each development period) to construct sRNA libraries. Then the eight prepared sRNA libraries were sequenced using Illumina next-generation sequencing technology on HiSeq 2500 platform. Results: As a result, we obtained 346 known and 187 novel miRNAs. Compared with the D70, 55 down- and 61 up-regulated miRNAs were shown to be significantly differentially expressed (DE). Gene ontology and Kyoto encyclopedia of genes and genomes enrichment analysis indicated that these DE miRNAs were mainly involved in growth, development and diverse metabolic processes. They were predicted to regulate lipid metabolism through adipocytokine signaling pathway, mitogen-activated protein kinase, AMP-activated protein kinase, cyclic adenosine monophosphate, phosphatidylinositol 3 kinase/protein kinase B, and Notch signaling pathway. The four most abundantly expressed miRNAs were miR-122, miR-26a and miR-30a-5p (miR-122 only in P70), which play important roles in lipid metabolism. Integration analysis (details of mRNAs sequencing data were shown in another unpublished paper) revealed that many target genes of the DE miRNAs (miR-181b, miR-145-5p, miR-199a-5p, and miR-98) might be critical regulators in lipid metabolic process, including acyl-CoA synthetase long chain family member 4, ATP-binding casette A4, and stearyl-CoA desaturase. Thus, these miRNAs were the promising candidates for lipid metabolism. Conclusion: Our study provides the main differences in the Large White at miRNA level between two different developmental stages. It supplies a valuable database for the further function and mechanism elucidation of miRNAs in porcine liver development and lipid metabolism.