Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 3.395
Filtrar
1.
J Environ Sci (China) ; 85: 138-146, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31471020

RESUMO

Arsenic (As) is an omnipresent metalloid toxicant, which has elicited serious environmental pollution and health risky problems. Previous studies have uncovered that the As exposure could also cause markedly reduction of serum triglycerides in mice. However, the regulation mechanisms are still largely unknown. The present study is aimed to elucidate the molecular mechanisms of lncRNAs in As-induced lipid metabolic disequilibrium. We demonstrated that lncRNA PU.1 AS was significantly induced in the liver of As-feed mice companied with lower serum triglycerides contents; further in vitro experiment confirmed that PU.1 AS regulated liver cells lipid accumulation by nile red fluorescence staining. Intensive mechanistic investigations illustrated that PU.1 AS could interact with EZH2 protein to regulate its downstream target gene expression, and As-induced PU.1 AS attenuated EZH2-supppressed Sirt6 expression, thereafter leading to a decreased SREBP-1c protein expression, as well as the diminished synthesis of triglycerides in hepatocytes. In conclusion, this study provided a new lncRNA-related regulatory signaling pathway participating in As-induced abnormal lipid metabolism.


Assuntos
Arsênico/metabolismo , Metabolismo dos Lipídeos/genética , Animais , Camundongos , RNA Longo não Codificante/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1 , Triglicerídeos
2.
Nat Commun ; 10(1): 2631, 2019 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-31201301

RESUMO

Men and women differ in circulating lipids and coronary artery disease (CAD). While sex hormones such as estrogens decrease CAD risk, hormone replacement therapy increases risk. Biological sex is determined by sex hormones and chromosomes, but effects of sex chromosomes on circulating lipids and atherosclerosis are unknown. Here, we use mouse models to separate effects of sex chromosomes and hormones on atherosclerosis, circulating lipids and intestinal fat metabolism. We assess atherosclerosis in multiple models and experimental paradigms that distinguish effects of sex chromosomes, and male or female gonads. Pro-atherogenic lipids and atherosclerosis are greater in XX than XY mice, indicating a primary effect of sex chromosomes. Small intestine expression of enzymes involved in lipid absorption and chylomicron assembly are greater in XX male and female mice with higher intestinal lipids. Together, our results show that an XX sex chromosome complement promotes the bioavailability of dietary fat to accelerate atherosclerosis.


Assuntos
Transtornos 46, XX do Desenvolvimento Sexual/metabolismo , Aterosclerose/genética , Metabolismo dos Lipídeos/genética , Lipídeos/sangue , Cromossomo X/fisiologia , Transtornos 46, XX do Desenvolvimento Sexual/sangue , Animais , Aterosclerose/sangue , Aterosclerose/metabolismo , Dieta Aterogênica/efeitos adversos , Modelos Animais de Doenças , Feminino , Hormônios Esteroides Gonadais/metabolismo , Humanos , Mucosa Intestinal/metabolismo , Intestino Delgado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Ovário/metabolismo , Fatores Sexuais , Proteína da Região Y Determinante do Sexo/genética , Testículo/metabolismo
3.
Food Chem Toxicol ; 131: 110558, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31175915

RESUMO

Effects of Spirulina platensis 55% ethanol extract (SPL55) on lipid metabolism in high-fat diet-induced hyperlipidaemic rats were investigated. Ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry indicated that SPL55 was enriched with polyunsaturated fatty acids. Meanwhile, serum and liver lipid levels, including total triglyceride, total cholesterol, and low-density-lipoprotein cholesterol, were significantly decreased in hyperlipidaemic rats of SPL55. Analysis of tissue sections showed that SPL55 treatment could markedly inhibit hepatic lipid accumulation and steatosis. Moreover, SPL55 regulated the mRNA and protein expression levels of SREBP-1c, HMG-CoA, PEPCK, ACC, and AMPK genes involved in lipid metabolism. Furthermore, SPL55 led to decrease the abundances of Turicibacter, Clostridium_XlVa, and Romboutsia, which were positive correlation with lipid metabolism indicators, and has also enriched Alloprevotella, Prevotella, Porphyromonadaceae, and Barnesiella. These results provided evidence that SPL55 might be developed as a functional food to ameliorate lipid metabolic disorders and hyperlipidaemia.


Assuntos
Ácidos Graxos Insaturados/farmacologia , Fígado Gorduroso/prevenção & controle , Microbioma Gastrointestinal/efeitos dos fármacos , Spirulina/química , Animais , Peso Corporal/efeitos dos fármacos , HDL-Colesterol/sangue , HDL-Colesterol/metabolismo , LDL-Colesterol/sangue , LDL-Colesterol/metabolismo , Dieta Hiperlipídica , Ácidos Graxos Insaturados/metabolismo , Expressão Gênica/efeitos dos fármacos , Metabolismo dos Lipídeos/genética , Fígado/patologia , Microalgas/química , Ratos , Ratos Wistar , Triglicerídeos/sangue , Triglicerídeos/metabolismo
4.
Aquat Toxicol ; 213: 105220, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31202166

RESUMO

Tamoxifen (TAM) is an antiestrogenic agent and can enter the aquatic environment in wastewater. It has been reported that TAM can induce hepatic steatosis in vertebrates, however, the effects of TAM exposure on lipid metabolism of hepatopancreas in crustaceans remains unclear. In this study, four TAM concentrations (0, 6.7, 13.4 and 20 µg g-1 crab body weight) were injected into the swimming-leg of swimming crabs Portunus trituberculatus, as a means of evaluating the effects of TAM on the expression levels of lipid metabolism-related genes, lipid composition, and hepatopancreas histology. The results showed that the mRNA levels of three lipogenic related genes (diacylglycerol acyltransferase 1 (DGAT1), acetyl-CoA carboxylase (ACC) and fatty acyl desaturase (FAD)) decreased significantly in the 6.7 µg g-1 and 20 µg g-1 TAM treatments compare to the control. The mRNA levels of fatty acid synthase (FAS) decreased significantly in a dose-dependent manner as TAM concentration increased. The mRNA levels of two lipid catabolism-related genes (acyl-CoA oxidase (ACOX) and fatty acid transport protein (FATP)) were down-regulated among the three TAM treatments, while the enzyme activity and mRNA level of carnitine palmitoyltransferase I (CPT-I) was up-regulated by TAM treatments. Compared to the control, the lowest levels of total lipids and phospholipids were detected in the 6.7 µg g-1 TAM treatment, while the 20 µg g-1 TAM treatment had the lowest free fatty acids concentration. The 6.7 µg g-1 TAM treatment had the lowest percentages of 16:1n-7, 18:1n-9, 18:1n-7 and total monounsaturated fatty acids (∑MUFA), whilst simultaneously recording the highest percentages of 18:2n-6 and 20:2n-6 in this treatment. Moreover, histological observations indicated that TAM caused the walls of the hepatopancreatic tubules to become brittle, with a concurrent increase in the number of blister-like cells. These results suggest that TAM damages the hepatopancreas and leads to a reduction in hepatopancreatic lipid deposition in P. trituberculatus.


Assuntos
Braquiúros/metabolismo , Hepatopâncreas/metabolismo , Hepatopâncreas/patologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Natação , Tamoxifeno/toxicidade , Animais , Braquiúros/efeitos dos fármacos , Carnitina O-Palmitoiltransferase/metabolismo , Ácidos Graxos não Esterificados/metabolismo , Feminino , Hepatopâncreas/efeitos dos fármacos , Metabolismo dos Lipídeos/genética , Oxirredução , Poluentes Químicos da Água/toxicidade
5.
Nat Cell Biol ; 21(6): 710-720, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31160709

RESUMO

The capacity of stem cells to self-renew or differentiate has been attributed to distinct metabolic states. A genetic screen targeting regulators of mitochondrial dynamics revealed that mitochondrial fusion is required for the maintenance of male germline stem cells (GSCs) in Drosophila melanogaster. Depletion of Mitofusin (dMfn) or Opa1 led to dysfunctional mitochondria, activation of Target of rapamycin (TOR) and a marked accumulation of lipid droplets. Enhancement of lipid utilization by the mitochondria attenuated TOR activation and rescued the loss of GSCs that was caused by inhibition of mitochondrial fusion. Moreover, constitutive activation of the TOR-pathway target and lipogenesis factor Sterol regulatory element binding protein (SREBP) also resulted in GSC loss, whereas inhibition of SREBP rescued GSC loss triggered by depletion of dMfn. Our findings highlight a critical role for mitochondrial fusion and lipid homeostasis in GSC maintenance, providing insight into the potential impact of mitochondrial and metabolic diseases on the function of stem and/or germ cells.


Assuntos
Proteínas de Drosophila/genética , Proteínas de Membrana/genética , Dinâmica Mitocondrial/genética , Células-Tronco/metabolismo , Proteínas de Ligação a Elemento Regulador de Esterol/genética , Animais , Diferenciação Celular/genética , Drosophila melanogaster/genética , Drosophila melanogaster/crescimento & desenvolvimento , Drosophila melanogaster/metabolismo , Homeostase , Metabolismo dos Lipídeos/genética , Masculino , Mitocôndrias/genética , Receptores Proteína Tirosina Quinases/genética , Transdução de Sinais/genética , Nicho de Células-Tronco/genética , Células-Tronco/citologia , Testículo/crescimento & desenvolvimento , Testículo/metabolismo
6.
Methodist Debakey Cardiovasc J ; 15(1): 62-69, 2019 Jan-Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31049151

RESUMO

Cardiovascular disease is the leading cause of death worldwide, and elevated lipid levels is a major contributor. Gene delivery, which involves controlled transfer of nucleic acids into cells and tissues, has been widely used in research to study lipid metabolism and physiology. Several technologies have been developed to somatically overexpress, silence, or disrupt genes in animal models and have greatly advanced our knowledge of metabolism. This is particularly true with regard to the liver, which plays a central role in lipoprotein metabolism and is amenable to many delivery approaches. In addition to basic science applications, many of these delivery technologies have potential as gene therapies for both common and rare lipid disorders. This review discusses three major gene delivery technologies used in lipid research-including adeno-associated viral vector overexpression, antisense oligonucleotides and small interfering RNAs, and the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 genome editing system-and examines their potential therapeutic applications.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Dislipidemias/terapia , Terapia Genética/métodos , Metabolismo dos Lipídeos/genética , Lipídeos/sangue , Animais , Sistemas CRISPR-Cas , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/genética , Dependovirus/genética , Dislipidemias/sangue , Dislipidemias/epidemiologia , Dislipidemias/genética , Edição de Genes/métodos , Terapia Genética/efeitos adversos , Vetores Genéticos , Humanos , Oligonucleotídeos Antissenso/genética , RNA Interferente Pequeno/genética , Terapêutica com RNAi/métodos , Resultado do Tratamento
7.
BMC Bioinformatics ; 20(Suppl 7): 195, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-31074374

RESUMO

BACKGROUND: Lipid metabolism reprogramming is a hallmark for tumor which contributes to tumorigenesis and progression, but the commonality and difference of lipid metabolism among pan-cancer is not fully investigated. Increasing evidences suggest that the alterations in tumor metabolism, including metabolite abundance and accumulation of metabolic products, lead to local immunosuppression in the tumor microenvironment. An integrated analysis of lipid metabolism in cancers from different tissues using multiple omics data may provide novel insight into the understanding of tumorigenesis and progression. RESULTS: Through systematic analysis of the multiple omics data from TCGA, we found that the most-widely altered lipid metabolism pathways in pan-cancer are fatty acid metabolism, arachidonic acid metabolism, cholesterol metabolism and PPAR signaling. Gene expression profiles of fatty acid metabolism show commonalities across pan-cancer, while the alteration in cholesterol metabolism and arachidonic acid metabolism differ with tissue origin, suggesting tissue specific lipid metabolism features in different tumor types. An integrated analysis of gene expression, DNA methylation and mutations revealed factors that regulate gene expression, including the differentially methylated sites and mutations of the lipid genes, as well as mutation and differential expression of the up-stream transcription factors for the lipid metabolism pathways. Correlation analysis of the proportion of immune cells in the tumor microenvironment and the expression of lipid metabolism genes revealed immune-related differentially expressed lipid metabolic genes, indicating the potential crosstalk between lipid metabolism and immune response. Genes related to lipid metabolism and immune response that are associated with poor prognosis were discovered including HMGCS2, GPX2 and CD36, which may provide clues for tumor biomarkers or therapeutic targets. CONCLUSIONS: Our study provides an integrated analysis of lipid metabolism in pan-cancer, highlights the perturbation of key metabolism processes in tumorigenesis and clarificates the regulation mechanism of abnormal lipid metabolism and effects of lipid metabolism on tumor immune microenvironment. This study also provides new clues for biomarkers or therapeutic targets of lipid metabolism in tumors.


Assuntos
Biomarcadores Tumorais/genética , Metilação de DNA , Regulação Neoplásica da Expressão Gênica , Metabolismo dos Lipídeos/genética , Neoplasias/genética , Neoplasias/metabolismo , Microambiente Tumoral/imunologia , Biologia Computacional/métodos , Perfilação da Expressão Gênica , Humanos , Mutação , Neoplasias/imunologia , Neoplasias/patologia , Transcriptoma , Microambiente Tumoral/genética
8.
Environ Sci Pollut Res Int ; 26(21): 21828-21834, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31134545

RESUMO

The effect of selenium on excessive fatty acid-induced apoptosis and abnormal amino acid metabolism in the liver is well known, because it is an important site in the fatty acid metabolism pathway. However, the protective role of nano-elemental selenium (nano-Se) supplementation against hexavalent chromium (K2Cr2O7)-induced abnormal fatty acid metabolism has not been evaluated yet. Therefore, we conducted chicken experiments with different nano-Se supplementation doses to investigate the role of nano-Se against Cr(VI)-induced adverse effects. For this purpose, a total of 120 1-day-old chicks were randomly divided into control group, Cr(VI)-exposed group, protection group, treatment group, prevention group, and nano-Se control group. The results of RT-qPCR showed that the nano-Se supplementation notably downregulated (P < 0.01) the messenger RNA (mRNA) expression levels of fatty acid synthase (FASN), whereas nano-Se supplementation significantly upregulated (P < 0.01) the mRNA expression level of acyl-coenzyme A oxidase 1 (ACOX1) in chicken's liver at day 35 of the experiment. Similar results were further verified by western blot analysis. Moreover, nano-Se supplementation significantly enhanced and reduced the antibody expression levels of ACOX1 and FASN in immunohistochemical analysis, respectively. Thus, finally, it was concluded that nano-Se can alleviate K2Cr2O7-induced abnormal fatty acid metabolism in chicken's liver.


Assuntos
Galinhas/metabolismo , Cromo/toxicidade , Ácidos Graxos/metabolismo , Fígado/efeitos dos fármacos , Selênio/farmacologia , Acil-CoA Oxidase/genética , Acil-CoA Oxidase/metabolismo , Animais , Apoptose/efeitos dos fármacos , Suplementos Nutricionais , Ácido Graxo Sintase Tipo I/genética , Ácido Graxo Sintase Tipo I/metabolismo , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Metabolismo dos Lipídeos/efeitos dos fármacos , Metabolismo dos Lipídeos/genética , Fígado/metabolismo , Nanopartículas/administração & dosagem , Nanopartículas/química , Substâncias Protetoras/farmacologia , Selênio/administração & dosagem , Selênio/química
9.
Life Sci ; 227: 201-211, 2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-31002917

RESUMO

AIMS: Colorectal cancer syndrome has been one of the greatest concerns in the world. Although several epidemiological studies have shown that hepatic low lipoprotein lipase (LPL) mRNA expression may be associated with dyslipidemia and tumor progression, it is still not known whether the liver plays an essential role in hyperlipidemia of ApcMin/+ mice. MAIN METHODS: We measured the expression of metabolic enzymes that involved fatty acid uptake, de novo lipogenesis (DNL), ß-oxidation and investigated hepatic triglyceride production in the liver of wild-type and ApcMin/+ mice. KEY FINDINGS: We found that hepatic fatty acid uptake and DNL decreased, but there was no significant difference in fatty acid ß-oxidation. Interestingly, the production of hepatic very low-density lipoprotein-triglyceride (VLDL-TG) decreased at 20 weeks of age, but marked steatosis was observed in the livers of the ApcMin/+ mouse. To further explore hypertriglyceridemia, we assessed the function of hepatic glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1 (GPIHBP1) for the first time. GPIHBP1 is governed by the transcription factor octamer-binding transcription factor-1 (Oct-1) which are involved in the nuclear factor-κB (NF-κB) signaling pathway in the liver of ApcMin/+ mice. Importantly, it was also confirmed that sn50 (100 µg/mL, an inhibitor of the NF-κB) reversed the tumor necrosis factor α (TNFα)-induced Oct-1 and GPIHBP1 reduction in HepG2 cells. SIGNIFICANCE: Altogether, these findings highlighted a novel role of GPIHBP1 that might be responsible for hypertriglyceridemia in ApcMin/+ mice. Hypertriglyceridemia in these mice may be associated with their hepatic lipid metabolism development.


Assuntos
Fígado/metabolismo , Receptores de Lipoproteínas/fisiologia , Triglicerídeos/metabolismo , Animais , Caquexia/metabolismo , Caquexia/fisiopatologia , Neoplasias do Colo/fisiopatologia , Ácidos Graxos/metabolismo , Fígado Gorduroso/patologia , Regulação da Expressão Gênica/genética , Células Hep G2 , Humanos , Hiperlipidemias/genética , Metabolismo dos Lipídeos/genética , Lipídeos/fisiologia , Lipogênese/fisiologia , Lipólise/fisiologia , Lipoproteínas VLDL/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fator 1 de Transcrição de Octâmero/fisiologia , Receptores de Lipoproteínas/genética , Receptores de Lipoproteínas/metabolismo , Triglicerídeos/genética , Fator de Necrose Tumoral alfa/fisiologia
10.
Lipids Health Dis ; 18(1): 103, 2019 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-31010439

RESUMO

BACKGROUND: Patients with diabetes mellitus were often accompanied with hyperlipidemia. ATP-binding cassette sub-family A member1 (ABCA1) promotes the efflux of lipids and thereby mediates the metabolism of cholesterol. The aim of our study was to determine the associations of ABCA1 gene polymorphisms with the risks of diabetes mellitus and dyslipidemia in diabetic patients. METHODS: We retrieved literature about the relationship between ABCA1 gene polymorphisms (C69T and R230C) and the risk of diabetes through PubMed, Web of Science, EMBASE, Wanfang Database, China National Knowledge Infrastructure (CNKI) and Cochrane database. Weighted mean difference (WMD) and odds ratio (OR) were used to compare continuous and dichotomous variables, respectively, accompanied by their 95% confidence interval (CI). RESULTS: A total of 1746 diabetic patients and 1292 non-diabetic controls were enrolled. All subjects were Caucasians. ABCA1 R230C T allele was significantly associated with reduced the risk of diabetes (OR = 0.75, 95% CI = 0.57-0.98, P = 0.04). There was no association of ABCA1 C69T gene polymorphisms with the risk of diabetes. However, subgroup analyses showed that the ABCA1 C69T gene mutation significantly reduced the risk of hypertriglyceridemia in diabetic patients as compared with that in non-diabetic subjects (dominant model: WMD =0.66, 95% CI = 0.52-0.8, P < 0.0001; recessive model: WMD = 0.47, 95%CI = 0.11-0.83, P = 0.01). CONCLUSIONS: ABCA1 R230C T allele gene mutation is a protective in decreasing the risk of diabetes in Caucasians and ABCA1 C69T gene mutation markedly influences the level of lipid metabolism in diabetic patients.


Assuntos
Transportador 1 de Cassete de Ligação de ATP/genética , Diabetes Mellitus/genética , Diabetes Mellitus/metabolismo , Metabolismo dos Lipídeos/genética , Mutação/genética , Genes Dominantes , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Viés de Publicação , Fatores de Risco
11.
Bull Exp Biol Med ; 166(6): 766-769, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31028586

RESUMO

The effect of sulfated polysaccharide from brown alga Fucus evanescens (fucoidan) administered via different routes (peroral and parenteral) on the dynamic of some lipid metabolism parameters and markers of systemic inflammation in mice with experimental dyslipidemia induced by prolonged administration of poloxamer P-407. It was found that fucoidan corrected the main parameters of lipid metabolism, reduced the level of endothelial dysfunction marker endothelin-1 and proinflammatory cytokines TNFα, IFNγ in blood serum in animals with experimental dyslipidemia. These findings open prospects for using fucoidan in the complex treatment of metabolic disorders and atherosclerotic inflammation.


Assuntos
Anti-Inflamatórios/farmacologia , Dislipidemias/tratamento farmacológico , Fucus/química , Regulação da Expressão Gênica/efeitos dos fármacos , Polissacarídeos/farmacologia , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , HDL-Colesterol/sangue , LDL-Colesterol/sangue , VLDL-Colesterol/sangue , Dislipidemias/induzido quimicamente , Dislipidemias/genética , Dislipidemias/imunologia , Endotelina-1/genética , Endotelina-1/imunologia , Inflamação/prevenção & controle , Interferon gama/genética , Interferon gama/imunologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Metabolismo dos Lipídeos/genética , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Poloxâmero/administração & dosagem , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Triglicerídeos/sangue , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia
12.
Lipids Health Dis ; 18(1): 84, 2019 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-30947712

RESUMO

BACKGROUND: Two important regulators for circulating lipid metabolisms are lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL). In relation to this, glycosylphosphatidylinositol anchored high-density lipoprotein binding protein 1 (GPIHBP1) has been shown to have a vital role in LPL lipolytic processing. However, the relationships between skeletal muscle mass and lipid metabolism, including LPL, GPIHBP1, and HTGL, remain to be elucidated. Demonstration of these relationships may lead to clarification of the metabolic dysfunctions caused by sarcopenia. In this study, these relationships were investigated in young Japanese men who had no age-related factors; participants included wrestling athletes with abundant skeletal muscle. METHODS: A total of 111 young Japanese men who were not taking medications were enrolled; 70 wrestling athletes and 41 control students were included. The participants' body compositions, serum concentrations of lipoprotein, LPL, GPIHBP1 and HTGL and thyroid function test results were determined under conditions of no extreme dietary restrictions and exercises. RESULTS: Compared with the control participants, wrestling athletes had significantly higher skeletal muscle index (SMI) (p < 0.001), higher serum concentrations of LPL (p < 0.001) and GPIHBP1 (p < 0.001), and lower fat mass index (p = 0.024). Kruskal-Wallis tests with Bonferroni multiple comparison tests showed that serum LPL and GPIHBP1 concentrations were significantly higher in the participants with higher SMI. Spearman's correlation analyses showed that SMI was positively correlated with LPL (ρ = 0.341, p < 0.001) and GPIHBP1 (ρ = 0.309, p = 0.001) concentration. The serum concentrations of LPL and GPIHBP1 were also inversely correlated with serum concentrations of triglyceride (LPL, ρ = - 0.198, p = 0.037; GPIHBP1, ρ = - 0.249, p = 0.008). Serum HTGL concentration was positively correlated with serum concentrations of total cholesterol (ρ = 0.308, p = 0.001), low-density lipoprotein-cholesterol (ρ = 0.336, p < 0.001), and free 3,5,3'-triiodothyronine (ρ = 0.260, p = 0.006), but not with SMI. CONCLUSIONS: The results suggest that increased skeletal muscle mass leads to improvements in energy metabolism by promoting triglyceride-rich lipoprotein hydrolysis through the increase in circulating LPL and GPIHBP1.


Assuntos
Lipase/sangue , Lipase Lipoproteica/sangue , Músculo Esquelético/metabolismo , Doenças Musculares/genética , Receptores de Lipoproteínas/sangue , Adolescente , Adulto , Atletas , LDL-Colesterol/sangue , Metabolismo Energético/genética , Exercício/fisiologia , Feminino , Estudos de Associação Genética , Humanos , Lipase/genética , Metabolismo dos Lipídeos/genética , Lipase Lipoproteica/genética , Fígado/metabolismo , Masculino , Músculo Esquelético/fisiologia , Doenças Musculares/sangue , Doenças Musculares/patologia , Receptores de Lipoproteínas/genética , Testes de Função Tireóidea , Triglicerídeos/sangue , Adulto Jovem
13.
Lipids Health Dis ; 18(1): 87, 2019 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-30954078

RESUMO

BACKGROUND: The homeostasis of lipid droplets (LDs) plays a crucial role in maintaining the physical metabolic processes in cells, and is regulated by many LD-associated proteins, including perilipin 5 (Plin5) in liver. As the putative sites of hepatitis C virus (HCV) virion assembly, LDs are vital to viral infection. In addition, the hepatic LD metabolism can be disturbed by non-structural HCV proteins, such as NS5A, but the details are still inexplicit. METHODS: HCV NS5A was overexpressed in the livers and hepatocytes of wild-type and Plin5-null mice. BODIPY 493/503 and oil red O staining were used to detect the lipid content in mouse livers and hepatocytes. The levels of lipids, lipid peroxidation and inflammation biomarkers were further determined. Immunofluorescence assay and co-immunoprecipitation assay were performed to investigate the relationship of Plin5 and NS5A. RESULTS: One week after adenovirus injection, livers expressing NS5A showed more inflammatory cell aggregation and more severe hepatic injuries in Plin5-null mice than in control mice, which was consistent with the increased serum levels of IL-2 and TNF-α (P < 0.05) observed in Plin5-null mice. Moreover, Plin5 deficiency in the liver and hepatocytes aggravated the elevation of MDA and 4-HNE levels induced by NS5A expression (P < 0.01). The triglyceride (TG) content was increased approximately 25% by NS5A expression in the wild-type liver and hepatocytes but was unchanged in the Plin5-null liver and hepatocytes. More importantly, Plin5 deficiency in the liver and hepatocytes exacerbated the elevation of non-esterified fatty acids (NEFAs) stimulated by NS5A expression (P < 0.05 and 0.01 respectively). Using triacsin C to block acyl-CoA biosynthesis, we found that Plin5 deficiency aggravated the NS5A-induced lipolysis of TG. In contrast, Plin5 overexpression in HepG2 cells ameliorated the NS5A-induced lipolysis and lipotoxic injuries. Immunofluorescent staining demonstrated that NS5A expression stimulated the targeting of Plin5 to the surface of the LDs in hepatocytes without altering the protein levels of Plin5. By co-IP, we found that the N-terminal domain (aa 32-128) of Plin5 was pivotal for its binding with NS5A. CONCLUSIONS: Our data highlight a protective role of Plin5 against hepatic lipotoxic injuries induced by HCV NS5A, which is helpful for understanding the steatosis and injuries in liver during HCV infection.


Assuntos
Fígado Gorduroso/genética , Hepatite C/genética , Fígado/metabolismo , Perilipina-5/genética , Proteínas não Estruturais Virais/genética , Acil Coenzima A/antagonistas & inibidores , Acil Coenzima A/biossíntese , Adenoviridae/genética , Animais , Modelos Animais de Doenças , Fígado Gorduroso/metabolismo , Fígado Gorduroso/terapia , Regulação Viral da Expressão Gênica/genética , Hepacivirus/genética , Hepacivirus/patogenicidade , Hepatite C/metabolismo , Hepatite C/patologia , Hepatite C/virologia , Hepatócitos/metabolismo , Hepatócitos/patologia , Hepatócitos/virologia , Humanos , Gotículas Lipídicas/metabolismo , Gotículas Lipídicas/patologia , Metabolismo dos Lipídeos/genética , Lipólise/genética , Fígado/lesões , Fígado/patologia , Fígado/virologia , Camundongos , Triazenos/administração & dosagem , Triglicerídeos/genética , Triglicerídeos/metabolismo , Fator de Necrose Tumoral alfa/genética
14.
Int J Mol Sci ; 20(5)2019 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-30836679

RESUMO

In clinical practice, there are patients with a combination of metabolic syndrome (MS) and chronic obstructive pulmonary disease (COPD). The pathological mechanisms linking MS and COPD are largely unknown. It remains unclear whether the effect of MS (possible obesity) has a major impact on the progression of COPD. This complicates the development of effective approaches for the treatment of patients with a diagnosis of MS and COPD. Experiments were performed on female C57BL/6 mice. Introduction of monosodium glutamate and extract of cigarette smoke was modeled to simulate the combined pathology of lipid disorders and emphysema. Biological effects of glucagon-like peptide 1 (GLP-1) and GLP-1 on endothelial progenitor cells (EPC) in vitro and in vivo were evaluated. Histological, immunohistochemical methods, biochemical methods, cytometric analysis of markers identifying EPC were used in the study. The CD31⁺ endothelial cells in vitro evaluation was produced by Flow Cytometry and Image Processing of each well with a Cytation™ 3. GLP-1 reduces the area of emphysema and increases the number of CD31⁺ endothelial cells in the lungs of mice in conditions of dyslipidemia and damage to alveolar tissue of cigarette smoke extract. The regenerative effects of GLP-1 are caused by a decrease in inflammation, a positive effect on lipid metabolism and glucose metabolism. EPC are proposed as pathogenetic and diagnostic markers of endothelial disorders in combination of MS with COPD. Based on GLP-1, it is proposed to create a drug to stimulate the regeneration of endothelium damaged in MS and COPD.


Assuntos
Peptídeo 1 Semelhante ao Glucagon/genética , Síndrome Metabólica/genética , Doença Pulmonar Obstrutiva Crônica/genética , Enfisema Pulmonar/genética , Animais , Fumar Cigarros/efeitos adversos , Modelos Animais de Doenças , Progressão da Doença , Células Progenitoras Endoteliais/metabolismo , Citometria de Fluxo , Glucose/metabolismo , Humanos , Metabolismo dos Lipídeos/genética , Pulmão/efeitos dos fármacos , Pulmão/patologia , Síndrome Metabólica/induzido quimicamente , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/tratamento farmacológico , Camundongos , Molécula-1 de Adesão Celular Endotelial a Plaquetas/genética , Doença Pulmonar Obstrutiva Crônica/induzido quimicamente , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Enfisema Pulmonar/diagnóstico , Enfisema Pulmonar/tratamento farmacológico , Enfisema Pulmonar/patologia , Glutamato de Sódio/toxicidade
15.
J Exp Clin Cancer Res ; 38(1): 116, 2019 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-30845964

RESUMO

BACKGROUND: Angiotensin II (ANGII) and its receptor (AGTR1) have been proposed as significant contributors to metastasis in multiple cancers. Further, high AGTR1 levels are associated with poor epithelial ovarian cancer (EOC) outcomes. However, the mechanistic basis for these effects is unknown. Recent studies have suggested that ovarian cancer metastasis is highly dependent on the formation of multicellular spheroids (MCS). To understand the associations between the ANGII/AGTR1 pathway and cancer outcomes, we evaluated the effects of ANGII on MCS formation by ovarian cancer cells and used a proteomic approach to analyze the mechanistic basis. METHODS: We used the data from the GENT database and immunohistochemistry staining to assess the AGTR1 expression in epithelial ovarian cancer (EOC) patients and to assess its role in cancer progression. Colony formation assay, 3D culture assay, and transwell assays were used to analyze the effect of ANGII on the MCS formation and cell migration. The signaling pathways of AGTR1 and transactivation of epidermal growth factor receptor (EGFR) transactivation were investigated by the western blotting analysis. Xenograft models were used to determine the role of AGTR1 in ovarian cancer metastasis. ANGII release from ovarian cancer cells and ANGII levels in the EOC ascites fluid were measured by immunoassay. A shotgun proteomic approach was used to explore the detail molecular mechanism. Modulation of lipid desaturation and endoplasmic reticulum stress were verified by the in vitro and in vivo functional assays. RESULTS: AGTR1 expression was negatively correlated with EOC prognosis. AGTR1activation significantly enhanced the MCS formation and cell migration. ANGII triggered both of the classical AGTR1 pathway and the EGFR transactivation. ANGII administration increased peritoneal metastasis. In addition, ovarian cancer cells secreted ANGII and enhanced cancer metastasis in a positive feedback manner. Based on the proteomic data, lipid desaturation was activated by induction of stearoyl-CoA desaturase-1 (SCD1), which suggests that inhibition of SCD1 may significantly reduce MCS formation by increasing endoplasmic reticulum stress. CONCLUSIONS: ANGII promotes MCS formation and peritoneal metastasis of EOC cells. AGTR1 activation increases the lipid desaturation via SCD1 upregulation, which ultimately reduces endoplasmic reticulum stress in MCS. This mechanism explained the association between high levels of AGTR1 and poor clinical outcomes in EOC patients.


Assuntos
Carcinoma Epitelial do Ovário/genética , Neoplasias Peritoneais/genética , Receptor Tipo 1 de Angiotensina/genética , Estearoil-CoA Dessaturase/genética , Angiotensina II/genética , Angiotensina II/metabolismo , Animais , Carcinoma Epitelial do Ovário/patologia , Movimento Celular/genética , Estresse do Retículo Endoplasmático/genética , Receptores ErbB/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Metabolismo dos Lipídeos/genética , Lipídeos/genética , Camundongos , Metástase Neoplásica , Neoplasias Peritoneais/patologia , Neoplasias Peritoneais/secundário , Prognóstico , Proteômica , Esferoides Celulares/metabolismo , Esferoides Celulares/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
16.
Lipids Health Dis ; 18(1): 55, 2019 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-30819205

RESUMO

BACKGROUND: Non-human primates (NHPs) are important models of medical research on obesity and cardiovascular diseases. As two of the most commonly used NHPs, cynomolgus macaque (CM) and African green monkey (AGM) own different capacities in lipid metabolism of which the mechanism is unknown. This study investigated the expression profiles of lipid metabolism-related microRNAs (miRNAs) in CM and AGM and their possible roles in controlling lipid metabolism-related gene expression. METHODS: By small RNA deep sequencing, the plasma miRNA expression patterns of CM and AGM were compared. The lipid metabolism-related miRNAs were validated through quantitative reverse-transcription (RT) polymerase chain reaction (PCR). Related-target genes were predicted by TargetScan and validated in Vero cells. RESULTS: Compared to CM, 85 miRNAs were upregulated with over 1.5-fold change in AGM of which 12 miRNAs were related to lipid metabolism. miR-122, miR-9, miR-185, miR-182 exhibited the greatest fold changes(fold changes are 51.2, 3.8, 3.7, 3.3 respectively; all P < 0.01). And 77 miRNAs were downregulated with over 1.5-fold change in AGM of which 3, miR-370, miR-26, miR-128 (fold changes are 9.3, 1.8, 1.7 respectively; all P < 0.05) were related to lipid metabolism. The lipid metabolism-related gene targets were predicted by TargetScan and confirmed in the Vero cells. CONCLUSION: We report for the first time a circulating lipid metabolism-related miRNA profile for CM and AGM, which may add to knowledge of differences between these two non-human primate species and miRNAs' roles in lipid metabolism.


Assuntos
Cercopithecus aethiops/genética , Metabolismo dos Lipídeos/genética , Lipídeos/sangue , Macaca fascicularis/genética , MicroRNAs/genética , Transportador 1 de Cassete de Ligação de ATP/sangue , Transportador 1 de Cassete de Ligação de ATP/genética , Animais , Carnitina O-Palmitoiltransferase/sangue , Carnitina O-Palmitoiltransferase/genética , Cercopithecus aethiops/sangue , Proteína 7 com Repetições F-Box-WD/sangue , Proteína 7 com Repetições F-Box-WD/genética , Ácido Graxo Sintase Tipo I/sangue , Ácido Graxo Sintase Tipo I/genética , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Ontologia Genética , Sequenciamento de Nucleotídeos em Larga Escala , Macaca fascicularis/sangue , MicroRNAs/sangue , Anotação de Sequência Molecular , Isoformas de Proteínas/sangue , Isoformas de Proteínas/genética , Receptores de Lipoproteínas/sangue , Receptores de Lipoproteínas/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Esterol O-Aciltransferase/sangue , Esterol O-Aciltransferase/genética , Células Vero
17.
BMC Genomics ; 20(1): 170, 2019 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-30832586

RESUMO

BACKGROUND: Intramuscular fat (IMF) content and composition have a strong impact on the nutritional and organoleptic properties of porcine meat. The goal of the current work was to compare the patterns of gene expression and the genetic determinism of IMF traits in the porcine gluteus medius (GM) and longissimus dorsi (LD) muscles. RESULTS: A comparative analysis of the mRNA expression profiles of the pig GM and LD muscles in 16 Duroc pigs with available microarray mRNA expression measurements revealed the existence of 106 differentially expressed probes (fold-change > 1.5 and q-value < 0.05). Amongst the genes displaying the most significant differential expression, several loci belonging to the Hox transcription factor family were either upregulated (HOXA9, HOXA10, HOXB6, HOXB7 and TBX1) or downregulated (ARX) in the GM muscle. Differences in the expression of genes with key roles in carbohydrate and lipid metabolism (e.g. FABP3, ORMDL1 and SLC37A1) were also detected. By performing a GWAS for IMF content and composition traits recorded in the LD and GM muscles of 350 Duroc pigs, we identified the existence of one region on SSC14 (110-114 Mb) displaying significant associations with C18:0, C18:1(n-7), saturated and unsaturated fatty acid contents in both GM and LD muscles. Moreover, we detected several genome-wide significant associations that were not consistently found in both muscles. Further studies should be performed to confirm whether these associations are muscle-specific. Finally, the performance of an eQTL scan for 74 genes, located within GM QTL regions and with available microarray measurements of gene expression, made possible to identify 14 cis-eQTL regulating the expression of 14 loci, and six of them were confirmed by RNA-Seq. CONCLUSIONS: We have detected significant differences in the mRNA expression patterns of the porcine LD and GM muscles, evidencing that the transcriptomic profile of the skeletal muscle tissue is affected by anatomical, metabolic and functional factors. A highly significant association with IMF composition on SSC14 was replicated in both muscles, highlighting the existence of a common genetic determinism, but we also observed the existence of a few associations whose magnitude and significance varied between LD and GM muscles.


Assuntos
Estudo de Associação Genômica Ampla , Metabolismo dos Lipídeos/genética , Músculo Esquelético/crescimento & desenvolvimento , Locos de Características Quantitativas/genética , Tecido Adiposo/crescimento & desenvolvimento , Tecido Adiposo/metabolismo , Animais , Regulação da Expressão Gênica no Desenvolvimento/genética , Humanos , Carne/análise , Músculo Esquelético/metabolismo , Músculos Paraespinais/crescimento & desenvolvimento , Músculos Paraespinais/metabolismo , Fenótipo , RNA Mensageiro/genética , Suínos/genética , Suínos/crescimento & desenvolvimento , Coxa da Perna/crescimento & desenvolvimento
18.
Genes Genomics ; 41(5): 583-597, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30830682

RESUMO

BACKGROUND: Strongylocentrotus nudus is an important cultured sea urchin species in north China, because its gonad is rich in unsaturated fatty acids, particularly long polyunsaturated fatty acids (LC-PUFAs). These PUFAs play pleiotropic and crucial roles in a wide range of biological process. OBJECTIVE: However, the genes contributing to biosynthesis PUFAs have not been elucidated yet, and the molecular mechanism relative to the difference in PUFA composition between male and female gonad as been revealed but the corresponding has not been understood. METHODS: In this paper, solexa sequencing based transcriptomic approach was used to identify and characterize the key genes relative to PUFA synthesis and further conducted different expressed genes between male and female gonad. RESULTS: A total of 130,124 transcripts and 189330 unigenes were de novo assembled from 64.32 Gb data. Next, these unigenes were subjected to functional annotation by mapping to six public databases, and this process revealed a lot of genes involving in lipid metabolism. In addition, three types of fatty acids front-end desaturase and three species of very long fatty acids elongase were identified and the pathway for PUFA biosynthesis was hypothesized. Last, comparative analysis revealed the higher expression level of Δ5 desaturase, Δ6 desaturase, ELOVL-4, -6 and -7 in male gonad compared with female. CONCLUSION: This results could plausible explain the differ in composition of PUFAs between male and female gonad of sea urchin.


Assuntos
Ácidos Graxos Insaturados/biossíntese , Perfilação da Expressão Gênica/métodos , Strongylocentrotus/genética , Animais , China , Ácidos Graxos , Ácidos Graxos Insaturados/genética , Feminino , Estudos de Associação Genética , Gônadas/metabolismo , Metabolismo dos Lipídeos/genética , Masculino , Strongylocentrotus/metabolismo , Transcriptoma/genética
19.
Nutrients ; 11(3)2019 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-30884788

RESUMO

Smaller cross-sectional studies and bariatric surgery trials suggest that weight loss may change the expression of genes in adipose tissue that have been implicated in the development of metabolic diseases, but well-powered intervention trials are lacking. In post hoc analyses of data from a 12-week dietary intervention trial initially designed to compare metabolic effects of intermittent vs. continuous calorie restriction, we analyzed the effects of overall weight loss on the subcutaneous adipose tissue (SAT) transcriptome. Changes in the transcriptome were measured by microarray using SAT samples of 138 overweight or obese individuals (age range: 35⁻65 years, BMI range: 25⁻40, non-smokers, non-diabetics). Participants were grouped post hoc according to the degree of their weight loss by quartiles (average weight loss in quartiles 1 to 4: 0%, -3.2%, -5.9%, and -10.7%). Candidate genes showing differential expression with weight loss according to microarray analyses were validated by reverse transcription quantitative polymerase chain reaction (RT-qPCR), and fold changes (FCs) were calculated to quantify differences in gene expression. A comparison of individuals in the highest vs. the lowest weight loss quartile revealed 681 genes to be differentially expressed (corrected p < 0.05), with 40 showing FCs of at least 0.4. Out of these, expression changes in secreted frizzled-related protein 2 (SFRP2, FC = 0.65, p = 0.006), stearoyl-CoA desaturase (SCD, FC = -1.00, p < 0.001), and hypoxia inducible lipid droplet-associated (HILPDA, FC = -0.45, p = 0.001) with weight loss were confirmed by RT-qPCR. Dietary weight loss induces significant changes in the expression of genes implicated in lipid metabolism (SCD and HILPDA) and WNT-signaling (SFRP2) in SAT.


Assuntos
Proteínas de Membrana/metabolismo , Proteínas de Neoplasias/metabolismo , Estearoil-CoA Dessaturase/metabolismo , Gordura Subcutânea/metabolismo , Perda de Peso/genética , Adulto , Idoso , Restrição Calórica/métodos , Estudos Transversais , Regulação para Baixo/genética , Feminino , Humanos , Metabolismo dos Lipídeos/genética , Masculino , Pessoa de Meia-Idade , Obesidade/dietoterapia , Obesidade/genética , Obesidade/metabolismo , Transcriptoma , Resultado do Tratamento , Via de Sinalização Wnt/genética
20.
EBioMedicine ; 42: 481-493, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30879920

RESUMO

BACKGROUND: Although significant progress has been made in understanding the mechanisms of steatosis and insulin resistance, the physiological functions of the epigenetic regulators in these processes remain largely elusive. METHODS: Hepatocyte-specific Arid1a knockout mice were administrated with high-fat diet (HFD) for 12 weeks, then insulin sensitivity was assessed by glucose tolerance test (GTT) and insulin tolerance test (ITT). The metabolism-related indicators were determined by employing a variety of biological methods, including histology, real-time PCR, enzyme-linked immunosorbent assay (ELISA), Western blotting assay, Chromatin immunoprecipitation (ChIP), RNA-seq and assay for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC-seq). FINDINGS: Hepatocyte-specific Arid1a deletion significantly increases susceptibility to develop hepatic steatosis, insulin resistance and inflammation in mice fed a HFD. In vitro, Arid1a deletion in isolated hepatocytes directly leads to free fatty acid-induced lipid accumulation and insulin resistance. Mechanically, Arid1a deficiency impairs fatty acid oxidation by downregulating PPARα and altering the epigenetic landscape of some metabolism genes. INTERPRETATION: These findings reveal that targeting Arid1a might be a promising therapeutic strategy for liver steatosis and insulin resistance. FUND: This work was supported by National Natural Science Foundation of China (81672772 and 81472621), China National Science and Technology Major Project for Prevention and Treatment of Infectious Diseases (No.2017ZX 10203207) and National Program on Key Research Project of China (grant no. 2016YFC0902701).


Assuntos
Proteínas de Ligação a DNA/genética , Resistência à Insulina/genética , Metabolismo dos Lipídeos/genética , Proteínas Nucleares/genética , Animais , Suscetibilidade a Doenças , Glucose/metabolismo , Hepatócitos/metabolismo , Histonas/metabolismo , Insulina/metabolismo , Fígado/metabolismo , Camundongos , Camundongos Knockout , Modelos Biológicos , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Receptores Ativados por Proliferador de Peroxissomo , Transdução de Sinais
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA