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Acta Pharmaceutica Sinica B 2024年第6期14卷 2716-2731页

作者： Yang Tong Pei An Puxian Tang Rui Mu Yuteng Zeng Hang Sun Mei Zhao Ziyan Lv Pan Wang Wanjun Han Chunshan Gui Xuechu Zhen Liang Han Jiangsu Key Laboratory of Neuropsychiatric Diseases and College of Pharmaceutical Sciences Soochow UniversitySuzhou 215123China Jiangsu Province Engineering Research Center of Precision Diagnostics and Therapeutics Development Soochow UniversitySuzhou 215123China

lipogenesis is often highly upregulated in breast cancer brain metastases to adapt to intracranial low lipid *** inhibitors hold therapeutic potential but their intra-tumoral distribution is often blocked by the blood-tumor barrier(BTB).BTB activates its Wnt signaling to maintain barrier properties,e.g.,Mfsd2a-mediated BTB low ***,we reported VCAM-1-targeting nano-wogonin(W@V-NPs)as an adjuvant of nano-orlistat(O@V-NPs)to intensify drug delivery and inhibit lipogenesis of brain metastases.W@V-NPs were proven to be able to inactivate BTB Wnt signaling,downregulate BTB Mfsd2a,accelerate BTB vesicular transport,and enhance tumor accumulation of O@*** the ability to specifically kill cancer cells in a lipid-deprived environment with IC_(50) at 48 ng/mL,W@V-NPs plus O@V-NPs inhibited the progression of brain metastases with prolonged survival of model *** combination did not induce brain edema,cognitive impairment,and systemic toxicity in healthy *** Wnt signaling could safely modulate the BTB to improve drug delivery and metabolic therapy against brain metastases.

关键词： lipogenesis Brain metastases Blood-tumor barrier Wnt signaling Drug delivery Fatty acid synthase Nanoparticles Combination therapy

Effect of dietary docosahexaenoic acid on lipogenesis and lipolysis in black sea bream,Acanthopagrus schlegeli

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Acta Oceanologica Sinica 2007年第1期26卷 112-121页

作者： JI Hong OM Ahamd Daud YOSHIMATSU Takao UMINO Testuya NAKAGAWA Heisuke FURUHASHI Makoto SAKAMOTO Shuichi College of Animal Science and Technology Northwest Agriculture and Forestry University Shaanxi 712100 China Graduate School of Biosphere Science Hiroshima University Higashi - hiroshima 739 - 8528 Japan Marine Finfish Production and Research Center Terengganu 22200 Malaysia Farming System Division National Research Institute of Aquaculture Fisheries Research Agency Mie 516 -0913 Japan Oriental Yeast Co Ltd Chiba 281 -0002 Japan

Hatchery-roared juvenile black sea breams are characterized by a low level of highly unsaturated fatty acids in their bodies, as compared with wild fish. To assess the effect of docosahaxaenoic acid （DHA） on lipegenic and lipelysis enzymes, one-year fish were roared on a casein-based purified diet and a DHA fortified diet （ 1.5% DHA ethyl ester/kg diet） for 60 d, followed with a period of 55 d for starvation. Dietary DHA was effectively incorporated into the fish body. Fortification of DHA depressed activities of glucose-6-phosphate dehydrogenase and NADP-isocitrate dehydrogenase as lipogenic enzymes in the hepatopancroas and intraperitoneal fat body. Carnitine palmitoyltransferase as lipolysis enzyme in the hepatopancreas was active in the DHA fortified fish. Starvation after feeding experiment induced increased carnitine palmitoyltransferase activity in both control and DHA fortified fish and the activity remained higher in the DHA fortified fish, while the monoenes were selectively consumed prior to highly unsaturated fatty acids. These results indicated that dietary DHA depressed lipogenesis and activated lipolysis.

关键词： DHA enzyme lipogenesis lipolysis black sea bream

Role of X-Box Binding Protein-1 in Fructose-Induced De Novo lipogenesis in HepG2 Cells

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Chinese Medical Journal 2018年第19期131卷 2310-2319页

作者： Xian Yu Lu-Ping Ren Chao Wang Ya-Jun Zhu Han-Ying Xing Jing Zhao Guang-Yao Song Department of Internal Medicine Hebei Medical University Shijiazhuang Hebei 050051 China Department of Endocrinology Hebei General Hospital Shijiazhuang Hebei 050051 China Hebei Key Laboratory of Metabolic Disease Hebei General Hospital Shijiazhuang Hebei 050051 China Department of Oncology Hebei General Hospital Shijiazhuang Hebei 050051 China

Background：A high consumption of fructose leads to hepatic *** 20-30% of triglycerides are synthesized via de novo *** studies showed that endoplasmic reticulum stress （ERS） is involved in this process,while others showed that a lipotoxic environment directly influences ER ***,our aim was to investigate the causal relationship between ERS and fatty acid synthesis and the effect of X-box binding protein-1 （XBP-1）,one marker of ERS,on hepatic lipid accumulation stimulated by high ***：HepG2 cells were incubated with different concentrations of *** regulators of de novo lipogenesis （i.e.,carbohydrate response element-binding protein [ChREBP] and sterol regulatory element-binding protein 1 c [SREBP-lc]） were measured by polymerase chain reaction and key lipogenic enzymes （acetyl-CoA carboxylase [ACC],fatty acid synthase [FAS],and stearoyl-CoA desaturase-1 [SCD-1]） by Western *** same lipogenesis-associated factors were then evaluated after exposure of HepG2 cells to high fructose followed by the ERS inhibitor tauroursodeoxycholic acid （TUDCA） or the ERS inducer ***,the same lipogenesis-associated factors were evaluated in HepG2 cells after XBP-1 upregulation or downregulation through cell ***：Exposure to high fructose increased triglyceride levels in a dose-and time-dependent manner and significantly increased mRNA levels of SREBP-1c and ChREBP and protein levels ofFAS,ACC,and SCD-1,concomitant with XBP-1 conversion to an active spliced ***-associated factors induced by high fructose were inhibited by TUDCA and induced by *** level in XBP-l-deficient group decreased significantly compared with high-fructose group （4.41 ± 0.54 μmol/g vs.6.52 ± 0.38 μmol/g,P 〈 0.001）,as mRNA expressions of SREBP-1c （2.92 ± 0.46 vs.5.08 ± 0.41,P 〈 0.01） and protein levels of FAS （0.53 ± 0.06 vs.0.85 ± 0.05,P =0.01）,SCD-1 （0.65 ± 0.06 vs.0.90 ± 0.04,P

关键词： Endoplasmic Reticulum Stress Fatty Liver lipogenesis X-Box Binding Protein-I

Pterostilbene induces cell apoptosis and inhibits lipogenesis in SKOV3 ovarian cancer cells by activation of AMPK-induced inhibition of Akt/mTOR signaling cascade

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BIOCELL 2021年第1期45卷 89-101页

作者： ATTALLA EL-KOTT EMAN ELBEALY FAHMY ELSAID HAITHAM EL-MEKKAWY ABD-EL-KARIM ABD-LATEIF ABDULALI TAWEEL HEBA KHALIFA AHMAD KANDEEL KAREEM MORSY ESSAM IBRAHIM MASHAEL MOHAMMED BIN-MEFERIJ Biology Department College of ScienceKing Khalid UniversityAbha61413Saudi Arabia Zoology Department College of ScienceDamanhour UniversityDamanhour22511Egypt Biology Department College of Science for GirlsKing Khalid UniversityAbha61413Saudi Arabia Zoology Department College of ScienceMansoura UniversityMansoura35511Egypt Zoology Department College of ScienceFayoum UniversityFayoum63511Egypt Zoology Department Faculty of ScienceAl-Zawia UniversityAl-ZawiaLibya Biology Department Faculty of ScienceCairo UniversityCairo12611Egypt Research Center for Advanced Materials Science(RCAMS) King Khalid UniversityAbha61413Saudi Arabia Blood Products Quality Control and Research Department National Organization for Research and Control of BiologicalsCairo12611Egypt Biology Department College of SciencePrincess Nourah bint Abdulrahman UniversityRiyadhSaudi Arabia

This study investigates if the anti-tumor effect of Pterostilbene in the SKOV3 ovarian cancer(OC)cell line involves inhibition of cell metabolism and tested in this effect involves modulating AMPK and Akt-induced regulation of ***,SKOV3 cells were cultured in the humidified conditions in DMEM media for 24 h with or without increasing concentration of ***,the cells were incubated with Pterostilbene(IC_(50)=50μM)under similar conditions with or without pre-incubation with Dorsomorphin,an AMPK *** a dose-dependent manner,Pterostilbene inhibited SKOV3 cell survival and increased their lysate levels of lactate dehydrogenase(LDH)and single-stranded DNA(ssDNA).When SKOV3 cells were treated with 50μM Pterostilbene,Pterostilbene significantly suppressed cell migration and invasion,reduced lysate levels of lactic acid and the optical density of Oil Red O staining,and increased lysate glucose *** also increased levels of malondialdehyde(MDA),reactive oxygen species(ROS),and induced intrinsic cell apoptosis by upregulating protein levels of Bax and cleaved caspase-3 and reducing protein levels of ***,Pterostilbene reduced mRNA levels of sterol regulatory element-binding protein 1(SREBP-1),fatty acid synthase(FAS),acetyl CoA carboxylase-1(ACC-1),and AMP-activated protein kinase(AMPK).Furthermore,Pterostilbene increased the protein levels of p-AMPK,p-p53,p-raptor,p-TSC-2,but significantly decreased protein levels of p-Akt,p-TSC-2,p-mTOR,p-S6K1,and *** with Dorsomorphin(CC)abolished all the anti-tumorigenesis effects afforded by Pterostilbene and prevented Pterostilbene-induced phosphorylation of Akt,p53,and *** conclusion,the tumorsuppressive effect of Pterostilbene in SKOV3 cells involves the induction of ROS and inhibition of dysregulation cell metabolism mainly due to AMPK-induced Akt-dependent or independent suppression of mTOR.

关键词： Pterostilbene Ovarian cancer lipogenesis Apoptosis AMPK

Three Important Transcription Factors Related to lipogenesis and Adipogenesis in Mammal

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Journal of Northeast Agricultural University(English Edition) 2010年第3期17卷 62-75页

作者： ZHANG Ying LI Hui College of Animal Sciences and Technology Northeast Agricultural University Harbin 150030 China

Lipid metabolism and adipocyte differentiation are reglulated by networking of transcription factors. It is generally known that three factors, peroxisome proliferator-activated receptor y （PPARγ）, CCAAT/element-binding protein a （C/EBPa） and sterol regulatory element binding protein-1 （SREBP1）, play fundamental roles in metabolic pathways. And they are also important in adipocyte differentiation. Expressions of these factors are regulated by some compounds such as fatty acids or some steroid hormones （insulin） which is stimulated by the nutritional level. Furthermore, these factors are related to some metabolic diseases including type II diabetes and obesity, Lots of researches have focused on relationships between the factors and the genetic diseases. Different functions of factors on inducing the adipocyte differentiation are other hot spots according to previous studies. This paper summarized these studies and gave a limpid description of structures and functions of these genes.

关键词： PPARγ C/EBPa SREBP1 lipogenesis adipogenesis

Cyanidine-3-O-Galactoside Enriched <i>Aronia melanocarpa</i>Extract Inhibits Adipogenesis and lipogenesis via Down-Regulation of Adipogenic Transcription Factors and Their Target Genes in 3T3-L1 Cells

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Food and Nutrition Sciences 2019年第2期10卷 128-147页

作者： Su-Min Lim Jae In Jung Nam Young Kim Jung-Shik Bae Hyun Sook Lee Eun Ji Kim Center for Efficacy Assessment and Development of Functional Foods and Drugs Hallym UniversityChuncheonRepublic of Korea R&D Center Wellfine Co.Ltd.ChuncheonRepublic of Korea Department of Food Science&Nutrition Dongseo UniversityBusanRepublic of Korea

Aronia melamocarpa (AM) is a rich source of anthocyanins, which are known to help prevent obesity. The cyanidine-3-O-galactoside enriched AM extract (AM-Ex) containing more cyanidine-3-O-galactoside than conventional AM extract was recently developed. The objective of this study was to examine the effect of AM-Ex on adipogenesis and its action mechanisms in vitro using 3T3-L1 adipocytes. To examine the anti-obesity effect of AM-Ex, 3T3-L1 cells were induced adipocyte differentiation and incubated with various concentration of AM-Ex. Lipid accumulation, cellular triglyceride content, mRNA expression of transcription factors and adipogenic genes were analyzed. Treatment with 100 - 400 μg/mL of AM-Ex resulted in a dose-dependent decrease in adipocyte differentiation and triglyceride accumulation. mRNA expression of adipogenic transcription factors, such as peroxisome proliferator-activated receptor gamma, CCAAT/enhancer binding protein α, sterol regulatory element-binding protein 1 were decreased. The level of gene expression of adipogenesis and lipogenesis-related genes, such as adipocyte protein 2, lipoprotein lipase, acetyl-CoA carboxylase, ATP-citrate lyase and fatty acid synthase were decreased. These results suggest that AM-Ex alleviated risk factors related to obesity by modulating multiple pathways associated with adipogenesis.

关键词： Obesity Adipocyte Adipogenesis lipogenesis Transcription Factor Adipocyte Protein 2

Gender-specific Effect of Deficient Abcg4 on lipogenesis in Mouse Brain

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Gender-specific Effect of Deficient Abcg4 on Lipogenesis in ...

Role of unfolded protein response in lipogenesis

药物基因组学和药物代谢酶及基因调控国际研讨会

作者： Jinmei Wu Shailesh B.Patel College of Biotechnology Jiangsu University of Science and Technology Department of Medicine Medical College of WisconsinMilwaukeeMisconsin 53226USA

＜正＞The mRNA levels of the genes for lipid lipogenesis as well as others were quantified in the brains of Abcg4 knockout and wild-type mice using quantitative *** results showed that different genes of lipid metabolism were activated in the brains of Abcg4-/-male and female mice,when compared to those of wildtype *** was shown that Abcg4 is a sex-regulated gene with the function of regulating fatty acid and/or cholesterol synthesis in the brain.

关键词： ATP-binding cassette transporter(ABC) abcg4 cholesterol lipogenesis gene knockout mouse quantitative PCR brain

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World Journal of Hepatology 2010年第6期2卷 203-207页

作者： Ze Zheng, Chunbin Zhang, Kezhong Zhang, Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI 48201, United States , Department of Immunology and Mic robiology, Wayne State University School of Medicine, Detroit, MI 48201, United States Ze Zheng Chunbin Zhang Kezhong Zhang Center for Molecular Medicine and Genetics Wayne State University School of Medicine Detroit MI 48201 United States.

The signal transduction network in regulating lipid metabolism is a hot topic of biomedical research. Recent research endeavors reveal that intracellular stress signaling from a cellular organelle called endoplasmic reticulum (ER) is critically involved in lipid homeostasis and the development of metabolic disease. The ER is a site where newly-synthesized proteins are folded and assembled into their three-dimensional structures, modified and transported to their precise cellular destinations. A wide range of biochemical, physiological and pathological stimuli can interrupt the protein folding process in the ER and cause accumulation of unfolded or misfolded proteins in the ER lumen, a condition referred to as ER stress. To cope with this stress condition, the ER has evolved highly-specifi c signaling pathways collectively termed Unfolded Protein Response (UPR) or ER stress response. The UPR regulates transcriptionaland translational programs, affecting broad aspects of cellular metabolism and cell fate. lipogenesis, the metabolic process of de novo lipid biosynthesis, occurs primarily in the liver where metabolic signals regulate expression of key enzymes in glycolytic and lipogenic pathways. Recent studies suggest that the UPR plays crucial roles in modulating lipogenesis under metabolic conditions. Here we address some of recent representative evidence regarding the role of the UPR in lipogenesis.

关键词： Endoplasmic reticulum stress Unfolded protein response lipogenesis Hepatic lipid metabolism Metabolic disease

A novel bellidifolin intervention mitigates nonalcoholic fatty liver disease-like changes induced by bisphenol F

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Journal of biomedical research 2024年第5期38卷 1-14页

作者： Jing Xue Linwei Zhang Jingxian Tao Xuexue Xie Xi Wang Linlin Wu Shuhu Du Ninghua Tan Yang Jin Jianming Ju Junting Fan Jun Wang Fei Huan Rong Gao Key Laboratory of Modern Toxicology Ministry of Education Department of Toxicology School of Public Health Nanjing Medical University Nanjing Jiangsu 211166 China. Taizhou Center for Disease Control and Prevention Taizhou Jiangsu 225300 China. Wuxi Center for Disease Control and Prevention Wuxi Jiangsu 214023 China. School of Pharmacy Jiangsu Province Engineering Research Center of Antibody Drug Nanjing Medical University Nanjing Jiangsu 211166 China. School of Traditional Chinese Pharmacy China Pharmaceutical University Nanjing Jiangsu 211198 China. Department of Pharmaceutical Analysis School of Pharmacy Nanjing Medical University Nanjing Jiangsu 211166 China. Affiliated Hospital of Integrated Traditional Chinese and Western Medicine Nanjing University of Chinese Medicine Nanjing Jiangsu 210028 China. Department of Hygienic Analysis and Detection Key Laboratory of Modern Toxicology Ministry of Education School of Public Health Nanjing Medical University Nanjing Jiangsu 211166 China.

As a potential endocrine-disrupting chemical, bisphenol F (BPF) may cause nonalcoholic fatty liver disease (NAFLD)-like changes, but the mechanisms underpinning its pathogenesis as well as the intervention strategies remain poorly understood. Using the electron microscopy technology, along with LipidTOX Deep Red neutral and Bodipy 493/503 staining assays, we observed that BPF treatment elicited a striking accumulation of lipid droplets in HepG2 cells, accompanied by an increased total level of triglycerides. At the molecular level, the lipogenesis-associated mRNAs and proteins, including acetyl-CoA carboxylase, fatty acid synthase, stearoyl-CoA desaturase-1, peroxisome proliferator-activated receptor gamma, and CCAAT-enhancer-binding proteins, increased significantly the AMP-activated protein kinase (AMPK)-mammalian target of rapamycin (mTOR) signaling regulation in both and studies. Furthermore, the immunofluorescence results also showed the robust lipogenesis induced by BPF, evident in its ability to promote the translocation of sterol regulatory element-binding protein-1c from the cytoplasm to the nuclei. To investigate the intervention strategies for BPF-induced NAFLD-like changes, we demonstrated that bellidifolin, isolated and purified from , significantly attenuated BPF-induced lipid droplet deposition in HepG2 cell and NAFLD-like changes in mice by blocking the expression of lipogenesis-associated proteins. Therefore, the present study elucidates the mechanisms underlying BPF-induced lipid accumulation in HepG2 cells, while also highlighting the potential of bellidifolin to mitigate BPF-induced NAFLD-like changes.

关键词： bellidifolin bisphenol F lipogenesis non-alcoholic fatty liver disease

GR-mediated transcriptional regulation of m^(6)A metabolic genes contributes to dietinduced fatty liver in hens

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Journal of Animal Science and Biotechnology 2022年第2期13卷 488-498页

作者： Yue Feng Yanlin Li Wenduo Jiang Yun Hu Yimin Jia Ruqian Zhao MOE Joint International Research Laboratory of Animal Health&Food Safety Nanjing Agricultural UniversityNanjingJiangsuP.R.China Key Laboratory of Animal Physiology&Biochemistry College of Veterinary MedicineNanjing Agricultural UniversityNanjingJiangsuP.R.China

Background:Glucocorticoid receptor(GR)mediated corticosterone-induced fatty liver syndrome(FLS)in the chicken by transactivation of Fat mass and obesity associated gene(FTO),leading to demethylation of N6-methyladenosine(m^(6)A)and post-transcriptional activation of lipogenic *** is considered the main cause of FLS in the modern poultry ***,this study was aimed to investigate whether GR and m^(6)A modification are involved in high-energy and low protein(HELP)diet-induced FLS in laying hens,and if true,what specific m^(6)A sites of lipogenic genes are modified and how GR mediates m^(6)A-dependent lipogenic gene activation in HELP diet-induced FLS in the ***:Laying hens fed HELP diet exhibit excess(P<0.05)lipid accumulation and lipogenic genes activation in the liver,which is associated with significantly increased(P<0.05)GR expression that coincided with global m^(6)A ***,the m^(6)A demethylase FTO is upregulated(P<0.05),whereas the m^(6)A reader YTHDF2 is downregulated(P<0.05)in the liver of FLS *** analysis identifies site-specific demethylation(P<0.05)of m^(6)A in the mRNA of lipogenic genes,including FASN,SREBP1 and ***,GR binding to the promoter of FTO gene is highly enriched(P<0.05),while GR binding to the promoter of YTHDF2 gene is diminished(P<0.05).Conclusions:These results implicate a possible role of GR-mediated transcriptional regulation of m^(6)A metabolic genes on m^(6)A-depenent post-transcriptional activation of lipogenic genes and shed new light in the molecular mechanism of FLS etiology in the chicken.

关键词： Chicken Fatty liver syndrome FTO GR lipogenesis m^(6)A YTHDF2