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1.
Microb Cell Fact ; 18(1): 163, 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31581944

RESUMO

BACKGROUND: Sustainable production of microbial fatty acids derivatives has the potential to replace petroleum based equivalents in the chemical, cosmetic and pharmaceutical industry. Most fatty acid sources for production oleochemicals are currently plant derived. However, utilization of these crops are associated with land use change and food competition. Microbial oils could be an alternative source of fatty acids, which circumvents the issue with agricultural competition. RESULTS: In this study, we generated a chimeric microbial production system that features aspects of both prokaryotic and eukaryotic fatty acid biosynthetic pathways targeted towards the generation of long chain fatty acids. We redirected the type-II fatty acid biosynthetic pathway of Escherichia coli BL21 (DE3) strain by incorporating two homologues of the beta-ketoacyl-[acyl carrier protein] synthase I and II from the chloroplastic fatty acid biosynthetic pathway of Arabidopsis thaliana. The microbial clones harboring the heterologous pathway yielded 292 mg/g and 220 mg/g DCW for KAS I and KAS II harboring plasmids respectively. Surprisingly, beta-ketoacyl synthases KASI/II isolated from A. thaliana showed compatibility with the FAB pathway in E. coli. CONCLUSION: The efficiency of the heterologous plant enzymes supersedes the overexpression of the native enzyme in the E. coli production system, which leads to cell death in fabF overexpression and fabB deletion mutants. The utilization of our plasmid based system would allow generation of plant like fatty acids in E. coli and their subsequent chemical or enzymatic conversion to high end oleochemical products.


Assuntos
Arabidopsis/genética , Proteínas de Escherichia coli/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Ácido Graxo Sintases/metabolismo , Ácidos Graxos/biossíntese , Engenharia Metabólica , 3-Oxoacil-(Proteína de Transporte de Acila) Sintase/síntese química , 3-Oxoacil-(Proteína de Transporte de Acila) Sintase/genética , 3-Oxoacil-(Proteína de Transporte de Acila) Sintase/metabolismo , Arabidopsis/enzimologia , Proteínas de Arabidopsis/síntese química , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Vias Biossintéticas , Escherichia coli/enzimologia , Proteínas de Escherichia coli/genética , Ácido Graxo Sintases/genética , Ácidos Graxos/química , Isoenzimas/síntese química , Isoenzimas/genética , Isoenzimas/metabolismo , Plasmídeos/genética , Plasmídeos/metabolismo
2.
J Food Sci ; 84(7): 1900-1908, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31183867

RESUMO

The quality of canola oil is affected by different extraction methods. The effect of cold-pressed canola oil (CPCO) diet and traditional refined bleached deodorized canola oil (RBDCO) diet on lipid accumulation and hepatic steatosis in mice were investigated. The body weight, peroxisome proliferator-activated receptor-α concentration, serum lipid profile, insulin sensitivity, and oxidative stress were increased in mice fed with CPCO diet, which had higher unsaturated fatty acid, tocopherols, phytosterols, and phospholipids but lower saturated fatty acid than RBDCO, after 12 weeks,. Moreover, CPCO significantly increased tocopherols and phytosterols content in liver and reduced liver cholesterol contents and lipid vacuoles accumulation than RBDCO. Also, serum proinflammatory cytokines, 3-hydroxy-3-methylglutary coenzyme A reductase expression level, lipogenic enzymes, and transcriptional factors such as sterol regulatory element-binding proteins 1c, acetyl-CoA carboxylase, and fatty acid synthase in the liver were also markedly downregulated from CPCO diet mice. Overall, CPCO can reduce lipid accumulation and hepatic steatosis by regulating oxidative stress and lipid metabolism in Kun Ming mice compared with RBDCO. PRACTICAL APPLICATION: The results suggested that more bioactive components were contained in cold-pressed canola oil (CPCO) rather than refined bleached deodorized canola oil (RBDCO). CPCO could lower the risk of obesity and hyperlipidemia, reduce lipid accumulation, and prevent hepatic steatosis. It could be considered as a kind of better edible oil than RBDCO.


Assuntos
Fígado Gorduroso/dietoterapia , Metabolismo dos Lipídeos , Estresse Oxidativo , Óleo de Brassica napus/química , Óleo de Brassica napus/metabolismo , Acetil-CoA Carboxilase/genética , Acetil-CoA Carboxilase/metabolismo , Animais , Colesterol/metabolismo , Ácido Graxo Sintases/genética , Ácido Graxo Sintases/metabolismo , Ácidos Graxos/análise , Fígado Gorduroso/genética , Fígado Gorduroso/metabolismo , Fígado Gorduroso/fisiopatologia , Humanos , Resistência à Insulina , Lipogênese , Fígado/metabolismo , Masculino , Camundongos , PPAR alfa/genética , PPAR alfa/metabolismo , Fosfolipídeos/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Triglicerídeos/metabolismo
3.
J Sci Food Agric ; 99(13): 5631-5637, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31106428

RESUMO

BACKGROUND: Chronic heat stress can enhance fat synthesis and result in lipid accumulation in the liver of broilers. To investigate the effects and molecular mechanisms of dietary taurine supplementation on fat synthesis and lipid accumulation in the liver of chronic heat-stressed broilers, 144 28 day-old chickens (Arbor Acres) were randomly distributed to normal control (NC, 22 °C, basal diet), heat stress (HS, consistent 32 °C, basal diet), or heat stress plus taurine (HS + T, consistent 32 °C, basal diet +5.00 g kg-1 taurine) groups for a 14-day feeding trial. RESULTS: Compared with those of the HS group, dietary taurine supplementation significantly decreased the level of very-low-density lipoprotein and the activity of aspartate aminotransferase in plasma and the relative weight of liver in the HS + T group. In addition, dietary taurine supplementation also significantly decreased the levels of triglyceride, acyl-CoA carboxylase (ACC) and fatty acid synthase (FAS), and suppressed the mRNA expression levels of liver X receptor α (LXRα), sterol response element-binding protein 1c, ACC and FAS in the liver of chronic heat-stressed broilers. Meanwhile, dietary taurine supplementation effectively alleviated lipid accumulation in the liver of broilers exposed to chronic heat stress. CONCLUSION: Chronic heat stress significantly increased fat synthesis and resulted in excess lipid deposition in the liver of broilers. Dietary taurine supplementation can effectively decrease fat synthesis by suppressing the LXRα pathway and alleviate lipid accumulation in the liver of chronic heat-stressed broilers. © 2019 Society of Chemical Industry.


Assuntos
Gorduras/metabolismo , Transtornos de Estresse por Calor/veterinária , Receptores X do Fígado/metabolismo , Fígado/efeitos dos fármacos , Doenças das Aves Domésticas/tratamento farmacológico , Taurina/administração & dosagem , Ração Animal/análise , Animais , Aspartato Aminotransferases/metabolismo , Galinhas , Suplementos Nutricionais/análise , Ácido Graxo Sintases/genética , Ácido Graxo Sintases/metabolismo , Feminino , Transtornos de Estresse por Calor/tratamento farmacológico , Transtornos de Estresse por Calor/genética , Transtornos de Estresse por Calor/metabolismo , Resposta ao Choque Térmico , Temperatura Alta , Lipoproteínas VLDL/metabolismo , Fígado/metabolismo , Receptores X do Fígado/genética , Masculino , Doenças das Aves Domésticas/genética , Doenças das Aves Domésticas/metabolismo , Doenças das Aves Domésticas/fisiopatologia , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Triglicerídeos/metabolismo
4.
Mol Med Rep ; 19(6): 5087-5096, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31059046

RESUMO

The present study aimed to investigate the inhibitory effects and the mechanisms underlying 17ß­estradiol (E2) effects on triglyceride synthesis and insulin resistance in skeletal muscle tissues and cells. Ovariectomy (OVX) was performed on 6­month­old female rats treated with or without E2. Subsequently, various serum biochemical markers were measured. Additionally, pathological alterations of the uterus, liver and skeletal muscle were analyzed, and the content of triglycerides (TG) in muscle was detected. Differentiated myotubes formed by C2C12 cells were treated with palmitic acid (PA) or pretreated with E2, estrogen receptor (ESR) 1 agonist propylpyrazoletriol (PPT) and ESR2 agonist diarylpropionitrile (DPN). Subsequently, the mRNA or protein expression levels of ESR1/2, peroxisome proliferator activated receptor α (PPARα), CD36 molecule (CD36), fatty acid synthase (FASN), perilipin 2 (PLIN2), phosphorylated acetyl­CoA carboxylase α (p­ACACA), p­AKT serine/threonine kinase (p­AKT) and p­mitogen­activated protein kinase 8 (p­MAPK8) were analyzed in skeletal muscle or in C2C12 cells by reverse transcription­semi­quantitative polymerase chain reaction and western blotting. The present results suggested that treatment with E2 inhibited OVX­induced body weight gain, TG accumulation and insulin resistance. The protein or mRNA expression levels of ESR1, CD36, PPARα, p­ACACA and p­AKT were decreased, whereas the protein or mRNA expression levels of ESR2, PLIN2, FASN and p­MAPK8 were increased in the OVX group. Of note, treatment with E2 restored the expression levels of the aforementioned factors. In C2C12 cells, treatment with E2 or PPT reversed the alterations induced by treatment with PA. In contrast, pretreatment with DPN did not influence the effect of PA. Collectively, E2 was able to interact with ESR1, thus activating the CD36­PPARα pathway, decreasing the level of TG in the muscles and improving insulin resistance in skeletal muscles and C2C12 cells.


Assuntos
Estradiol/farmacologia , Receptor alfa de Estrogênio/metabolismo , Triglicerídeos/biossíntese , Animais , Linhagem Celular , Regulação para Baixo/efeitos dos fármacos , Receptor alfa de Estrogênio/agonistas , Receptor alfa de Estrogênio/genética , Receptor beta de Estrogênio/genética , Receptor beta de Estrogênio/metabolismo , Ácido Graxo Sintases/genética , Ácido Graxo Sintases/metabolismo , Feminino , Resistência à Insulina , Camundongos , Músculo Esquelético/citologia , Músculo Esquelético/metabolismo , Ovariectomia , Ácido Palmítico/farmacologia , Perilipina-2/genética , Perilipina-2/metabolismo , Fenóis/farmacologia , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Pirazóis/farmacologia , Ratos , Ratos Sprague-Dawley , Regulação para Cima/efeitos dos fármacos
5.
Biosci Biotechnol Biochem ; 83(9): 1740-1746, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31021712

RESUMO

Sterol regulatory element-binding proteins (SREBPs) are transcription factors that regulate the expression of genes involved in fatty acid and cholesterol biosynthetic pathways. The present study showed that the flavonoid chrysin impairs the fatty acid synthase promoter. Chrysin reduces the expression of SREBP target genes, such as fatty acid synthase, in human hepatoma Huh-7 cells and impairs de novo synthesis of fatty acids and cholesterol. Moreover, it reduces the endogenous mature, transcriptionally active forms of SREBPs, which are generated by the proteolytic processing of precursor forms. In addition, chrysin reduces the enforced expressing mature forms of SREBPs and their transcriptional activity. The ubiquitin-proteasome system is not involved in the chrysin-mediated reduction of SREBPs mature forms. These results suggest that chrysin suppresses SREBP activity, at least partially, via the degradation of SREBPs mature forms. Abbreviations: ACC1: acetyl-CoA carboxylase 1; DMEM: Dulbecco's modified Eagle's medium; FAS: fatty acid synthase; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; 25-HC: 25-hydroxycholesterol; HMGCS: HMG-CoA synthase; LDH: lactate dehydrogenase; LPDS: lipoprotein-deficient serum; PI3K: phosphatidylinositol 3-kinase; SCD1: stearoyl-CoA desaturase; SREBPs: sterol regulatory element-binding proteins.


Assuntos
Flavonoides/farmacologia , Proteínas de Ligação a Elemento Regulador de Esterol/metabolismo , Animais , Linhagem Celular Tumoral , Colesterol/biossíntese , Ácido Graxo Sintases/genética , Ácidos Graxos/biossíntese , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Regiões Promotoras Genéticas , Proteólise , Proteínas de Ligação a Elemento Regulador de Esterol/antagonistas & inibidores , Proteínas de Ligação a Elemento Regulador de Esterol/genética
6.
J Agric Food Chem ; 67(16): 4623-4631, 2019 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-30950260

RESUMO

Propiconazole is a triazole fungicide that has been widely used in agriculture and has been detected in the aquatic environment. This study aimed to investigate the effects of propiconazole exposure on lipid metabolism in the early life stages of zebrafish for 120 h postfertilization (hpf). Using the early life stages of zebrafish to address scientific questions is lower in cost, more efficient, and suitable to meeting current legislation than those in other traditional fish species. Exposure to propiconazole significantly inhibited the development of zebrafish embryos and larvae. This exposure also caused reduced locomotor activities in zebrafish. Furthermore, total cholesterol levels, lipoprotein lipase, and fatty acid synthase activities were significantly decreased. The expression levels of genes involved in lipid metabolism were significantly up-regulated in response to propiconazole exposure. GC-MS/MS analysis revealed that fatty acids were significantly decreased. Together, the findings indicate the potential environmental risks of propiconazole exposure in the aquatic ecosystem.


Assuntos
Fungicidas Industriais/toxicidade , Metabolismo dos Lipídeos/efeitos dos fármacos , Triazóis/toxicidade , Peixe-Zebra/embriologia , Animais , Ácido Graxo Sintases/genética , Ácido Graxo Sintases/metabolismo , Feminino , Lipase Lipoproteica/genética , Lipase Lipoproteica/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Peixe-Zebra/metabolismo , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo
7.
Lipids Health Dis ; 18(1): 89, 2019 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-30954075

RESUMO

BACKGROUND: Elevation of exogenous free fatty acid (FFA) level leads to insulin resistance (IR) in liver, IR is manifested by elevated hepatic glucose production. We aim to study whether inhibition of endogenous fatty acid synthesis could decrease hepatic glucose production. METHODS: Low-passage HepG2 cells derived from human liver tissue were cultured in medium supplemented with FFA to induce IR, the influences of sterol regulatory element binding protein-1c (SREBP-1c) silencing on glucose production of HepG2 cells were investigated, and genes responsible for fatty acid and glucose metabolism were detected by real-time PCR. RESULTS: Compared with HepG2 cells cultured in normal growth medium, glucose production of HepG2 cells treated by FFA was significantly increased {[(0.28 ± 0.01) vs (0.83 ± 0.02)] umol.ug- 1 protein, n = 6 wells, P < 0.01}; the mRNA expression of phosphoenolpyruvate carboxylase kinase (PEPCK) and glucose-6-phosphatase (G6PC) in HepG2 cells increased by more than 5-fold and 3-fold, respectively; the mRNA expression of fatty acid synthase (FAS) and stearoyl-CoA desaturase-1 (SCD1) increased by approximately 4-fold and 1.1-fold, respectively; the mRNA expression of carnitine palmitoyltransferase-1 (CPT-1) changed slightly. Compared with the scrambled siRNA control, glucose production of HepG2 cells treated by FFA significantly increased after SREBP-1c silencing {[(0.018 ± 0.001) vs (0.028 ± 0.002)] umol.ug- 1 protein, n = 6 wells, P < 0.01}; the mRNA expression of PEPCK and G6PC increased by approximately 1.5-fold and 5-fold, respectively, but the mRNA expression of FAS, SCD1 and CPT-1 changed slightly. CONCLUSIONS: SREBP-1c silencing further augmented glucose production of HepG2 cells treated by FFA significantly, genes responsible for fatty acid synthesis and gluconeogenesis played an important role in this process. SREBP-1c functions not only as a lipid regulator but also plays an important role in regulation of glucose metabolism.


Assuntos
Meios de Cultura/farmacologia , Ácidos Graxos não Esterificados/farmacologia , Glucose/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Carnitina O-Palmitoiltransferase/genética , Ácido Graxo Sintases/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Inativação Gênica/efeitos dos fármacos , Células Hep G2 , Humanos , Resistência à Insulina/genética , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipídeos/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/antagonistas & inibidores , Triglicerídeos/metabolismo
8.
Food Funct ; 10(4): 1940-1947, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30874277

RESUMO

Vitexin, a bioactive compound isolated from hawthorn leaf extracts, has been reported to exhibit many biological activities, such as anticancer, antioxidation, and adipogenesis inhibition activities. The current study explored the effects of vitexin on high fat diet (HFD)-induced obesity/adipogenesis in male C57BL/6J mice and 3T3-L1 adipocytes, as well as the underlying mechanisms thereof. Vitexin significantly mitigated HFD-induced body weight gain and adiposity. Vitexin also partially normalized serum, hepatic lipid contents, and decreased adipocyte size induced by the HFD. Consistently, there were significant effects of vitexin on important regulators of lipid metabolism, including AMP-activated protein kinase-α (AMPKα), CAATT element binding protein-α (C/EBPα), and fatty acid synthase (FAS) in white adipose tissue. Moreover, vitexin significantly inhibited fat accumulation in 3T3-L1 adipocytes, and this was totally abolished by compound C (an AMPKα inhibitor). These results suggest that vitexin may prevent HFD-induced obesity/adipogenesis via the AMPKα mediated pathway.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Fármacos Antiobesidade/administração & dosagem , Apigenina/administração & dosagem , Obesidade/tratamento farmacológico , Células 3T3-L1 , Proteínas Quinases Ativadas por AMP/genética , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Animais , Proteína alfa Estimuladora de Ligação a CCAAT/genética , Proteína alfa Estimuladora de Ligação a CCAAT/metabolismo , Dieta Hiperlipídica/efeitos adversos , Ácido Graxo Sintases/genética , Ácido Graxo Sintases/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/etiologia , Obesidade/genética , Obesidade/metabolismo , Transdução de Sinais/efeitos dos fármacos
9.
Planta ; 249(6): 1823-1836, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30847571

RESUMO

MAIN CONCLUSION: The enzymes HaKCS1 and HaKCS2 are expressed in sunflower seeds and contribute to elongation of C18 fatty acids, resulting in the C20-C24 fatty acids in sunflower oil. Most plant fatty acids are produced by plastidial soluble fatty acid synthases that produce fatty acids of up to 18 carbon atoms. However, further acyl chain elongations can take place in the endoplasmic reticulum, catalysed by membrane-bound synthases that act on acyl-CoAs. The condensing enzymes of these complexes are the ketoacyl-CoA synthase (KCSs), responsible for the synthesis of very long chain fatty acids (VLCFAs) and their derivatives in plants, these including waxes and cuticle hydrocarbons, as well as fatty aldehydes. Sunflower seeds accumulate oil that contains around 2-3% of VLCFAs and studies of the fatty acid elongase activity in developing sunflower embryos indicate that two different KCS isoforms drive the synthesis of these fatty acids. Here, two cDNAs encoding distinct KCSs were amplified from RNAs extracted from developing sunflower embryos and named HaKCS1 and HaKCS2. These genes are expressed in developing seeds during the period of oil accumulation and they are clear candidates to condition sunflower oil synthesis. These two KCS cDNAs complement a yeast elongase null mutant and when expressed in yeast, they alter the host's fatty acid profile, proving the encoded KCSs are functional. The structure of these enzymes was modelled and their contribution to the presence of VLCFAs in sunflower oil is discussed based on the results obtained.


Assuntos
Acetiltransferases/metabolismo , Helianthus/enzimologia , Modelos Estruturais , Óleo de Girassol/metabolismo , Acetiltransferases/química , Acetiltransferases/genética , Acil Coenzima A/metabolismo , Aldeídos/metabolismo , Sequência de Aminoácidos , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , DNA Complementar/genética , Ácido Graxo Sintases/química , Ácido Graxo Sintases/genética , Ácido Graxo Sintases/metabolismo , Ácidos Graxos/metabolismo , Helianthus/genética , Filogenia , Proteínas de Plantas/química , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Sementes/enzimologia , Sementes/genética , Alinhamento de Sequência
10.
Yeast ; 36(3): 143-151, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30677185

RESUMO

Cyclopropane fatty acids, which can be simply converted to methylated fatty acids, are good unusual fatty acid candidates for long-term resistance to oxidization and low-temperature fluidity useful for oleochemistry and biofuels. Cyclopropane fatty acids are present in low amounts in plants or bacteria. In order to develop a process for large-scale biolipid production, we expressed 10 cyclopropane fatty acid synthases from various organisms in the oleaginous yeast Yarrowia lipolytica, a model yeast for lipid metabolism and naturally capable of producing large amounts of lipids. The Escherichia coli cyclopropane fatty acid synthase expression in Y. lipolytica allows the production of two classes of cyclopropane fatty acids, a C17:0 cyclopropanated form and a C19:0 cyclopropanated form, whereas others produce only the C17:0 form. Expression optimization and fed-batch fermentation set-up enable us to reach a specific productivity of 0.032 g·L-1 ·hr-1 with a genetically modified strain containing cyclopropane fatty acid up to 45% of the total lipid content corresponding to a titre of 2.3 ± 0.2 g/L and a yield of 56.2 ± 4.4 mg/g.


Assuntos
Ciclopropanos/metabolismo , Ácido Graxo Sintases/metabolismo , Ácidos Graxos/metabolismo , Engenharia Metabólica/métodos , Proteínas Recombinantes/metabolismo , Yarrowia/genética , Yarrowia/metabolismo , Ciclopropanos/química , Ácido Graxo Sintases/genética , Ácidos Graxos/química , Fermentação , Expressão Gênica , Redes e Vias Metabólicas/genética , Proteínas Recombinantes/genética , Yarrowia/crescimento & desenvolvimento
11.
Lipids Health Dis ; 18(1): 11, 2019 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-30621686

RESUMO

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is closely linked to obesity, type 2 diabetes and other metabolic disorders worldwide. Crocin is a carotenoid compound possessing various pharmacological activities. In the present study, we aimed to investigate the effect on fatty liver under diabetic and obese condition and to examine the possible role of AMP-activated protein kinase (AMPK) signaling. METHODS: db/db mice were administrated with crocin and injected with LV-shAMPK or its negative control lentivirus. Metabolic dysfunction, lipogenesis and fatty acid-oxidation in liver were evaluated. RESULTS: In db/db mice, we found that oral administration of crocin significantly upregulated the phosphorylation of AMPK and downregulated the phosphorylation of mTOR in liver. Crocin reduced liver weight, serum levels of alanine aminotransferase, alanine aminotransferase, and liver triglyceride content, and attenuated morphological injury of liver in db/db mice. Crocin inhibited the mRNA expression of lipogenesis-associated genes, including sterol regulatory element binding protein-1c, peroxisome proliferator-activated receptor γ, fatty acid synthase, stearoyl-CoA desaturase 1, and diacylglycerol acyltransferase 1, and increased the mRNA expression of genes involved in the regulation of ß-oxidation of fatty acids, including PPARα, acyl-CoA oxidase 1, carnitine palmitoyltransferase 1, and 3-hydroxy-3-methylglutaryl-CoA synthase 2. Moreover, treatment of crocin resulted in a amelioration of general metabolic disorder, as evidenced by decreased fasting blood glucose, reduced serum levels of insulin, triglyceride, total cholesterol, and non-esterified fatty acid, and improved glucose intolerance. Crocin-induced protective effects against fatty liver and metabolic disorder were significantly blocked by lentivirus-mediated downregulation of AMPK. CONCLUSIONS: The results suggest that crocin can inhibit lipogenesis and promote ß-oxidation of fatty acids through activation of AMPK, leading to improvement of fatty liver and metabolic dysfunction. Therefore, crocin may be a potential promising option for the clinical treatment for NAFLD and associated metabolic diseases.


Assuntos
Proteínas Quinases Ativadas por AMP/genética , Fármacos Antiobesidade/farmacologia , Carotenoides/farmacologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/farmacologia , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Proteínas Quinases Ativadas por AMP/metabolismo , Acil-CoA Oxidase/genética , Acil-CoA Oxidase/metabolismo , Alanina Transaminase/sangue , Alanina Transaminase/genética , Animais , Aspartato Aminotransferases/sangue , Aspartato Aminotransferases/genética , Carnitina O-Palmitoiltransferase/genética , Carnitina O-Palmitoiltransferase/metabolismo , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Diacilglicerol O-Aciltransferase/antagonistas & inibidores , Diacilglicerol O-Aciltransferase/genética , Diacilglicerol O-Aciltransferase/metabolismo , Modelos Animais de Doenças , Ácido Graxo Sintases/antagonistas & inibidores , Ácido Graxo Sintases/genética , Ácido Graxo Sintases/metabolismo , Regulação da Expressão Gênica , Hidroximetilglutaril-CoA Sintase/genética , Hidroximetilglutaril-CoA Sintase/metabolismo , Lipogênese/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Transgênicos , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , PPAR alfa/agonistas , PPAR alfa/genética , PPAR alfa/metabolismo , PPAR gama/antagonistas & inibidores , PPAR gama/genética , PPAR gama/metabolismo , Transdução de Sinais , Estearoil-CoA Dessaturase/antagonistas & inibidores , Estearoil-CoA Dessaturase/genética , Estearoil-CoA Dessaturase/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/antagonistas & inibidores , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Resultado do Tratamento , Triglicerídeos/sangue
12.
Ecotoxicol Environ Saf ; 167: 29-35, 2019 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-30292973

RESUMO

Perfluorooctanoic acid (PFOA) is a perfluorinated compound that is widely distributed, is persistent in the environment, and has a low-level chronic exposure effect on human health. The aim of this study was to investigate the peroxisome proliferator activated receptors γ (PPARγ) and the sterol regulatory element-binding protein 2 (SREBP2) signaling pathways in regulating the lipid damage response to PFOA in the livers of amphibians. Male and female frogs (Rana nigromaculata) were exposed to 0, 0.01, 0.1, 0.5 and 1 mg/L PFOA. After treatment, we evaluated the pathological changes in the liver by Oil Red O, staining and examined the total cholesterol (T-CHO) and triglyceride (TG) contents. The mRNA expression levels of PPARγ, Fatty acid synthase (FAS), Acetyl-CoA carboxylase (ACC), Glycerol-3-phosphate acyltransferase (GPAT), SREBP2 and 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) were measured by quantitative real-time polymerase chain reaction (qRT-PCR). The administration of PFOA caused marked lipid accumulation damage in the amphibian livers. The T-CHO contents were elevated significantly after PFOA treatment; these results show a dose-dependent manner in both sexes. The TG content showed a significant increase in male livers, while it was elevated significantly in female livers. The RT-PCR results showed that the mRNA expression levels of PPARγ, ACC, FAS, GPAT, SREBP2 and HMG-CoA were significantly dose-dependently increased in the PFOA-treated groups compared with those of the control group. Our results demonstrated that PFOA-induced lipid accumulation also affected the expression levels of genes FAS, ACC, GPAT and HMG-CoA in the PPARγ and SREBP2 signaling pathways in the liver. These finding will provide a scientific theoretical basis for the protection of Rana nigromaculata against PFOA effects.


Assuntos
Caprilatos/toxicidade , Fluorcarbonetos/toxicidade , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Ranidae/metabolismo , Acil Coenzima A/metabolismo , Animais , Colesterol/metabolismo , Relação Dose-Resposta a Droga , Ácido Graxo Sintases/genética , Ácido Graxo Sintases/metabolismo , Feminino , Fígado/metabolismo , Masculino , PPAR gama/genética , PPAR gama/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 2/genética , Proteína de Ligação a Elemento Regulador de Esterol 2/metabolismo , Triglicerídeos/metabolismo
13.
BMC Genomics ; 19(1): 932, 2018 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-30547741

RESUMO

BACKGROUND: Regulatory circuits of infection in the emerging experimental model system, water flea Daphnia and their microparasites, remain largely unknown. Here we provide the first molecular insights into the response of Daphnia galeata to its highly virulent and common parasite Caullerya mesnili, an ichthyosporean that infects the gut epithelium. We generated a transcriptomic dataset using RNAseq from parasite-exposed (vs. control) Daphnia, at two time points (4 and 48 h) after parasite exposure. RESULTS: We found a down-regulation of metabolism and immunity-related genes, at 48 h (but not 4 h) after parasite exposure. These genes are involved in lipid metabolism and fatty acid biosynthesis, as well as microbe recognition (e.g. c-type lectins) and pathogen attack (e.g. gut chitin). CONCLUSIONS: General metabolic suppression implies host energy shift from reproduction to survival, which is in agreement with the known drastic reduction in Daphnia fecundity after Caullerya infection. The down-regulation of gut chitin indicates a possible interaction between the peritrophic matrix and the evading host immune system. Our study provides the first description of host transcriptional responses in this very promising host-parasite experimental system.


Assuntos
Daphnia/genética , Sistema Imunitário/metabolismo , Intestinos/parasitologia , Metabolismo dos Lipídeos/genética , Mesomycetozoea/fisiologia , Animais , Daphnia/metabolismo , Regulação para Baixo , Ácido Graxo Sintases/genética , Interações Hospedeiro-Parasita , Sistema Imunitário/parasitologia , RNA/química , RNA/isolamento & purificação , RNA/metabolismo , Análise de Sequência de RNA , Transcriptoma
14.
Oxid Med Cell Longev ; 2018: 3914384, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30363969

RESUMO

Hypercholesterolemia is a metabolic disorder associated with oxidative stress. The present study investigated the protective effect of Monolluma quadrangula extract on hypercholesterolemia-induced oxidative stress in the liver and heart of high-cholesterol-diet- (HCD-) fed rats. The experimental animals received HCD for 10 weeks and were concurrently treated with 300 or 600 mg/kg M. quadrangula extract. HCD-fed rats showed a significant increase in serum triglycerides, total cholesterol, LDL-cholesterol, vLDL-cholesterol, and cardiovascular risk indices along with decreased HDL-cholesterol and antiatherogenic index. The M. quadrangula extract significantly improved dyslipidemia and atherogenesis in HCD-fed rats. HCD induced a significant increase in serum transaminases, creatine kinase-MB, and proinflammatory cytokines. In addition, HDC induced a significant increase in hepatic and cardiac lipid peroxidation and decreased antioxidant enzymes. Treatment with the M. quadrangula extract significantly alleviated liver and heart function markers, decreased proinflammatory cytokines and lipid peroxidation, and enhanced the antioxidant defenses. Also, the M. quadrangula extract significantly reduced the expression of fatty acid synthase (FAS) and increased the expression of LDL receptor in the liver of HCD-fed rats. In conclusion, the M. quadrangula extract has a potent antihyperlipidemic and cholesterol-lowering effect on HCD-fed rats. The beneficial effects of the M. quadrangula extract were mediated through the increased antioxidant defenses, decreased inflammation and lipid peroxidation, and modulated hepatic FAS and LDL receptor gene expression.


Assuntos
Apocynaceae/química , Ácido Graxo Sintases/genética , Hipercolesterolemia/tratamento farmacológico , Hipercolesterolemia/genética , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/uso terapêutico , Substâncias Protetoras/uso terapêutico , Receptores de LDL/genética , Animais , Antioxidantes/metabolismo , Aterosclerose/sangue , Aterosclerose/tratamento farmacológico , Aterosclerose/patologia , Proteína C-Reativa/metabolismo , Colesterol na Dieta , Citocinas/sangue , Ácido Graxo Sintases/metabolismo , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Hipercolesterolemia/sangue , Hipercolesterolemia/patologia , Peroxidação de Lipídeos/efeitos dos fármacos , Lipídeos/sangue , Fígado/efeitos dos fármacos , Fígado/patologia , Fígado/fisiopatologia , Masculino , Miocárdio/metabolismo , Miocárdio/patologia , Extratos Vegetais/farmacologia , Substâncias Protetoras/farmacologia , Ratos Wistar , Receptores de LDL/metabolismo
15.
Arch Insect Biochem Physiol ; 99(2): e21495, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30003605

RESUMO

Total fatty acids in the pea aphid reared at low temperatures increased significantly compared to that at high rearing temperatures. This change is reflected in a large increase of myristic acid, which occurs exclusively in triacylglycerols. When aphids were moved from 25°C to a lower rearing temperature at 10°C, saturated fatty acids accumulated over time, reaching a maximum at 16th day. When aphids were moved to 4°C, a temperature below the developmental threshold, those aphids did not accumulate saturated fatty acids. Similar results were observed when aphids were exposed to sequential decrease in rearing temperature. However, both total fatty acids and myristic acid in the aphids from the treatments of sequential decreasing rearing temperature were significantly higher compared to those in the aphids from the treatments of sudden decreasing rearing temperature. This result, therefore, supports the hypothesis that cold-adapted aphids can survive under threshold temperature for a longer period of time than noncold-adapted aphids. Acetyl-CoA carboxylase activity in the aphids at 25°C was twofold higher than that in the aphids at 10°C, whereas fatty acid synthase activities in the aphids reared at 25 and 10°C are similar. Aphids reared at 10°C showed a threefold reduction in reproduction rates. This reduced production of new nymphs reduces energy demand and would allow for accumulation of energy in the form of triacylglycerols. Therefore, the increased level of saturated fatty acids in aphids reared at low temperature is probably related to lower utilization of fatty acids rather than increased rates of biosynthesis.


Assuntos
Acetil-CoA Carboxilase/genética , Afídeos/metabolismo , Temperatura Baixa , Ácido Graxo Sintases/genética , Ácidos Graxos/metabolismo , Acetil-CoA Carboxilase/metabolismo , Animais , Afídeos/crescimento & desenvolvimento , Ácido Graxo Sintases/metabolismo , Ninfa/crescimento & desenvolvimento , Ninfa/metabolismo , Triglicerídeos/metabolismo
16.
Food Funct ; 9(7): 3755-3763, 2018 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-29897085

RESUMO

Obesity is a risk factor for many chronic diseases, and the anti-obesity effect of starch in a whole grain-like structural form (WGLSF) prepared through co-gelation with oat ß-glucan and alginate was studied using high-fat (HF) induced obese male C57BL/6J mice. In vitro human fecal fermentation of WGLSF-starch showed a slower rate of fermentation and a higher production of butyric acid (132.0 µmol per 50 mg sample) when compared to the physical mixture counterpart of starch, ß-glucan, and alginate (PM) (110.5 µmol per 50 mg) or ß-glucan itself (96.2 µmol per 50 mg). The body weight gain of obese mice fed with a HF-WGLSF diet was significantly reduced (42.0% lower than the HF group, 30.2% lower than the physical mixture) with decreased cell size in white adipose tissue and similar levels of serum lipid profiles to the control of the low-fat (LF) group. Western blotting experiments showed the down-regulated lipogenic transcription factor of SREBP-1c and fatty acid synthase (FAS), but the lipid-oxidation related transcription factors of peroxisome proliferator-activated receptor-α (PPAR-α) and phosphorylated AMP-activated protein kinase (p-AMPK) were up-regulated. Energy metabolism analysis revealed increased lipid-sourced energy expenditure with higher heat production and respiratory exchange ratios. Consistently, the expression of hypothalamic pro-opiomelanocortin (POMC), favoring energy expenditure, was increased significantly while the neuropeptide Y (NPY) was reduced. Thus, the increased energy expenditure stimulated by starch in a whole-grain-like structural form is responsible for the reduced body weight gain of obese mice fed with a high fat-based diet.


Assuntos
Fármacos Antiobesidade/metabolismo , Obesidade/dietoterapia , Amido/química , Amido/metabolismo , Grãos Integrais/metabolismo , Adipogenia , Animais , Metabolismo Energético , Ácido Graxo Sintases/genética , Ácido Graxo Sintases/metabolismo , Humanos , Metabolismo dos Lipídeos , Lipogênese , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Obesidade/genética , Obesidade/metabolismo , PPAR alfa/genética , PPAR alfa/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Grãos Integrais/química
17.
Int J Mol Sci ; 19(6)2018 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-29904032

RESUMO

Phloretin, a glucose transporter (GLUT) inhibitor, has pleiotropic effects. The present study examined the effects of phloretin on the commitment of marrow stromal cells to adipocytes, using the mouse marrow stromal cell line ST2. Oil red O staining showed that treatment with phloretin 10⁻100 µM promoted lipid accumulation. Real-time PCR showed that phloretin significantly increased the expression of adipogenic markers, including PPARγ, C/EBPα, fatty acid synthase, fatty acid-binding protein 4, and adiponectin. Western blotting showed that phloretin inhibited ERK1/2 and JNK but activated p38 MAPK. Treatment with a MAPK/ERK kinase inhibitor and a JNK inhibitor enhanced adipogenesis, similar to phloretin. In contrast, a p38 MAPK inhibitor suppressed phloretin-induced adipogenesis. Although phloretin phosphorylated AMP-activated protein kinase (AMPK), co-incubation with an AMPK inhibitor did not block phloretin-induced adipogenesis. The 2-deoxyglucose colorimetric assay showed that phloretin and siRNA silencing of GLUT1 decreased glucose uptake. However, unlike phloretin treatment, GLUT1 silencing inhibited adipogenesis. In addition, phloretin enhanced adipogenesis in GLUT1 knocked-down cells. Taken together, phloretin induced adipogenesis of marrow stromal cells by inhibiting ERK1/2 and JNK and by activating p38 MAPK. The adipogenic effects of phloretin were independent of glucose uptake inhibition. Phloretin may affect energy metabolism by influencing adipogenesis and adiponectin expression.


Assuntos
Adipogenia , Células da Medula Óssea/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases , Células-Tronco Mesenquimais/efeitos dos fármacos , Floretina/farmacologia , Adiponectina/genética , Adiponectina/metabolismo , Animais , Células da Medula Óssea/citologia , Células da Medula Óssea/metabolismo , Linhagem Celular , Ácido Graxo Sintases/genética , Ácido Graxo Sintases/metabolismo , Proteínas de Ligação a Ácido Graxo/genética , Proteínas de Ligação a Ácido Graxo/metabolismo , Transportador de Glucose Tipo 1/genética , Transportador de Glucose Tipo 1/metabolismo , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Camundongos , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , PPAR gama/genética , PPAR gama/metabolismo , Proteínas Quinases/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
18.
Fish Shellfish Immunol ; 80: 97-108, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29860070

RESUMO

The present study aimed to investigate the effect of low phosphorus diet with or without different levels of phytase enzyme supplementation on growth performance, body composition, nutrient retention efficiency, gene expression, and health status of A. hydrophila challenged fish. A total of 240 monosex males of Nile tilapia (Oreochromis niloticus) with an average body weight of 23.19 ±â€¯0.15 g/fish were used. Fish were randomly chosen and divided into 4 equal groups (60 fish per group), with 3 subgroups containing 20 fish as a replicate. Group 1, was fed on a diet containing 100% P, group 2, was fed on a diet containing 50% P, group 3 and 4, were fed on low P with 500 or 1000 units of phytase/Kg respectively. It was observed that the 50% phosphorus diet significantly reduced body weight, feed intake, feed conversion ratio (FCR), and protein efficiency ratio (PER) compared to Nile tilapia fish fed on the diet containing 100% phosphorus. In contrast, fish fed on the diet containing 50% phosphorus supplemented by 500 or 1000 phytase units/kg significantly (P ≤ 0.05) increased final body weight (FBW), total body gain (TBG), average daily gain (ADG), and weight gain compared to Nile tilapia fed on the same diet or fed on the diet containing normal phosphorus without phytase supplementation. Different phosphorus and phytase supplementation levels had no significant effect on serum total protein, albumin, and globulin concentrations, meanwhile, phytase supplementation increased serum calcium and phosphorus levels. Nile tilapia fed on phytase supplementation had an increase in body protein, lipid content, and nutrient utilization efficiency compared to Nile tilapia fed on the diet containing 100% phosphorus. Nile tilapia fed on low dietary phosphorus showed an increase in mortality after infection and a decrease in phagocytosis and neutrophil compared to fish fed on normal phosphorus. Phytase supplementation, made immune response parameters return to its normal values and the pathological lesions of liver, spleen, stomach, and intestine were reduced. Moreover, normal phosphorus significantly up-regulated lipoprotein lipase (LPL) mRNA expression and down-regulated fatty acid synthase (FAS) mRNA in Nile tilapia's liver while low phosphorus with or without phytase supplementation reduced LPL expression and relatively up-regulated FAS.


Assuntos
6-Fitase/farmacologia , Ciclídeos , Fósforo na Dieta/farmacologia , Aeromonas hydrophila , Animais , Peso Corporal/efeitos dos fármacos , Ciclídeos/sangue , Ciclídeos/genética , Ciclídeos/crescimento & desenvolvimento , Ciclídeos/imunologia , Ingestão de Alimentos/efeitos dos fármacos , Ácido Graxo Sintases/genética , Doenças dos Peixes/imunologia , Proteínas de Peixes/genética , Expressão Gênica/efeitos dos fármacos , Infecções por Bactérias Gram-Negativas/imunologia , Infecções por Bactérias Gram-Negativas/veterinária , Intestinos/efeitos dos fármacos , Intestinos/patologia , Contagem de Leucócitos , Lipase Lipoproteica/genética , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Fagocitose/efeitos dos fármacos , Baço/efeitos dos fármacos , Baço/patologia , Estômago/efeitos dos fármacos , Estômago/patologia
19.
Int J Mol Med ; 42(3): 1215-1228, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29786745

RESUMO

Non­alcoholic fatty liver disease (NAFLD) is a manifestation of metabolic syndrome in the liver and is closely associated with diabetes; however, its pathogenesis remains to be elucidated. Carbohydrate responsive element binding protein (ChREBP), the hub of glucolipid metabolism, regulates the induction of fatty acid synthase (FASN), the key enzyme of de novo lipogenesis, by directly binding to carbohydrate response element (ChoRE) in its promoter. Investigations of histone modifications on NAFLD remain in their infancy. In the present study, by using ChIP, the association between histone modifications and FASN transcription was investigated and histone modifications in FASN modulated by ChREBP were measured. It was demonstrated that ChREBP induced FASN ChREBP­ChoRE binding to accelerate the expression of FASN, leading to hepatocellular steatosis by facilitating H3 and H4 acetylation, H3K4 trimethylation and the phosphorylation of H3S10, but inhibiting the trimethylation of H3K9 and H4K20 in FASN promoter regions of HepG2 and L02 cells. It was also found that ChREBP­ChoRE binding of FASN relied on histone acetylation and that the transcriptional activity of ChREBP on FASN is required, based on the premise that histone acetylation causes conformational changes in FASN chromatin. This indicated histone acetylation as a crucial mechanism involved in the transcription of FASN modulated by ChREBP. Consequently, the present study provides further insight into the pathophysiology and a novel therapeutic potential of NAFLD based on epigenetic mechanisms.


Assuntos
Ácido Graxo Sintases/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Western Blotting , Linhagem Celular , Ácido Graxo Sintases/genética , Glucose/farmacologia , Células Hep G2 , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Código das Histonas/efeitos dos fármacos , Código das Histonas/genética , Humanos , Lipogênese/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/genética , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , Processamento de Proteína Pós-Traducional/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa
20.
Lipids Health Dis ; 17(1): 114, 2018 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-29759071

RESUMO

BACKGROUND: The prevalence of nonalcoholic fatty liver disease (NAFLD) has increased worldwide. Metformin decreases triglyceride (TG) accumulation in hepatocytes in vivo and in vitro. Stearyl-coenzyme A desaturase 1 (SCD1) knockout mice also show decreased liver TG accumulation; however, whether SCD1 plays a role in the effect of metformin on TG accumulation is unknown. Therefore, the aim of this study was to investigate whether SCD1 mediated the effect of metformin on TG accumulation. METHODS: HepG2 and AML12 cells were exposed to high glucose and high insulin with or without metformin. An adenovirus was used for the SCD1 knockdown and overexpression. The triglyceride level in cells was detected. The expression of related genes was detected by Western blot and quantitative real-time PCR. A dual-luciferase reporter assay was used to determine the effect of metformin on the transcriptional activity of the SCD1 promoter. RESULTS: Metformin decreased TG accumulation to normal level in HepG2 cells exposed to high glucose and high insulin. The expression of SCD1 and fatty acid synthetase (FAS) was also decreased to normal level by metformin. Knockdown of SCD1 mimicked the effect of metformin on decreasing TG levels in AML12 cells, and the overexpression of SCD1 attenuated the effect of metformin on decreasing TG accumulation in HepG2 cells. The dual-luciferase reporter assay showed that the transcriptional activity of the SCD1 promoter (- 550/+ 199) after metformin treatment was 2-fold lower compared to control group in HepG2 cells. Additionally, the phosphorylation of AMPK after metformin treatment was 2-fold higher, and the expression of sterol regulatory element-binding protein-1c (SREBP-1c) after metformin treatment was about 2-fold lower compared to high glucose and high insulin group in HepG2 cells. CONCLUSIONS: Together, these results reveal that metformin reduces TG accumulation in HepG2 cells via inhibiting the expression of SCD1.


Assuntos
Hepatócitos/efeitos dos fármacos , Hipoglicemiantes/farmacologia , Metformina/farmacologia , Estearoil-CoA Dessaturase/genética , Triglicerídeos/metabolismo , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Adenoviridae/genética , Adenoviridae/metabolismo , Animais , Linhagem Celular , Ácido Graxo Sintases/genética , Ácido Graxo Sintases/metabolismo , Regulação da Expressão Gênica , Genes Reporter , Vetores Genéticos/química , Vetores Genéticos/metabolismo , Glucose/farmacologia , Células Hep G2 , Hepatócitos/citologia , Hepatócitos/metabolismo , Humanos , Insulina/farmacologia , Luciferases/genética , Luciferases/metabolismo , Camundongos , Regiões Promotoras Genéticas , Transdução de Sinais , Estearoil-CoA Dessaturase/antagonistas & inibidores , Estearoil-CoA Dessaturase/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Triglicerídeos/antagonistas & inibidores
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