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1.
J Agric Food Chem ; 67(31): 8485-8492, 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31304752

RESUMO

How short-chain fatty acids (FAs) affect cell membrane morphology and milk fat biosynthesis in mammary epithelial cells (MECs) is yet unclear. This study investigated the primary bovine MEC response to different FAs. We observed that the cell surface ultrastructures were influenced by chain length and degree of saturability of FAs. The CD36, FATP1, and FABP3 gene expression was affected independent of the type of FA. FASN, LPIN1, PPARα, and PPARγ transcripts were more sensitive to the short-chain FAs (acetic and ß-hydroxybutyric acids). Furthermore, short-chain FAs inclined to regulate FA degradation-, elongation-, and metabolism-associated pathways, while long-chain FAs (stearic and trans-10,cis-12 conjugated linolenic acids) modulated extracellular matrix-receptor interaction-, transcriptional misregulation-, microRNA-, and ribosome biogenesis-related pathways. However, triacylglycerol accumulation in the cytoplasm was not changed by all of the FAs. Overall, FAs with different chain lengths and degrees of saturability could differentially alter primary bovine MEC cell morphology and influence protein profiles involved in milk fat synthesis pathways.


Assuntos
Bovinos/metabolismo , Células Epiteliais/metabolismo , Gorduras/metabolismo , Ácidos Graxos não Esterificados/química , Ácidos Graxos não Esterificados/metabolismo , Glândulas Mamárias Animais/metabolismo , Leite/metabolismo , Animais , Antígenos CD36/genética , Antígenos CD36/metabolismo , Bovinos/genética , Gorduras/química , Proteínas de Transporte de Ácido Graxo/genética , Proteínas de Transporte de Ácido Graxo/metabolismo , Feminino , Glândulas Mamárias Animais/citologia , Leite/química , PPAR alfa/genética , PPAR alfa/metabolismo , Triglicerídeos/metabolismo
2.
Dis Markers ; 2019: 5702026, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31089396

RESUMO

The increased requirement of fatty acids forces cancer cells to enhance uptake of fatty acids from the extracellular milieu, in addition to de novo lipogenesis. Coexpression of cluster of differentiation 36 (CD36) with fatty acid transport protein 4 (FATP4) or long-chain acyl CoA synthetase 1 (ACSL1) synergistically activated fatty acid uptake in experimental models. In this study, we investigated the immunohistochemical expression of CD36, FATP4, and ACSL1 in 180 cases of clear cell renal cell carcinoma (RCC) in comparison with 80 specimens of the normal kidney. We also examined the clinical implication of these three fatty acid transporters in RCC, which was validated by an open-access The Cancer Genome Atlas data analysis. Both CD36 and FATP4 revealed higher membranous expressions in RCC tumor cells than in normal cells. In contrast, ACSL1 expression was remarkably reduced in RCC tumor cells compared to normal cells. CD36, FATP4, and ACSL1 showed high expressions in 74 (41.1%), 85 (47.2%), and 72 (40.0%) out of 180 RCC cases, respectively. Clinically, high FATP4 in tumor cells was associated with female gender (p = 0.05), high TNM stage (p = 0.039), tumor necrosis (p = 0.009), and tumor recurrence (p = 0.037), while high ACSL1 was only related to female gender (p = 0.023). CD36 expression revealed no correlation with the clinicopathologic parameters of RCC. Increased FATP4 expression displayed an association with short recurrence-free survival (p = 0.003). In conclusion, the high FATP4 expression was clinically associated with poor prognostic factors of RCC. Overexpression of membranous FATP4 and CD36 combined with reduced cytoplasmic expression of ACSL1 might be a tumor-specific feature of RCC, contributing to the tumorigenesis and tumor progression.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinogênese/genética , Carcinoma de Células Renais/metabolismo , Coenzima A Ligases/metabolismo , Proteínas de Transporte de Ácido Graxo/metabolismo , Neoplasias Renais/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Antígenos CD36/genética , Antígenos CD36/metabolismo , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Membrana Celular/metabolismo , Coenzima A Ligases/genética , Proteínas de Transporte de Ácido Graxo/genética , Feminino , Humanos , Neoplasias Renais/genética , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade
3.
J Anim Sci ; 97(6): 2342-2356, 2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-30958881

RESUMO

Bacterial infection causes nutrient malabsorption in small intestine. KR-32, a kind of synthetic antimicrobial peptide, has the bacteriostatic effect. In the present study, 2 experiments were designed to analyze the effects of KR-32 on fat absorption of piglets with or without Escherichia coli infection. In Exp. 1, 12 weaning piglets (21 d old) were allocated to 2 groups: piglets with an intraperitoneal (i.p.) injection of antimicrobial peptide KR-32 (APK) and piglets with an i.p. injection of an equivalent volume (1 mL) of phosphate-buffered saline (PBS) (CON-1). Results showed that after 7 d of growth, KR-32 did not significantly change growth performance and apparent total tract digestibility (ATTD) of feed nutrients of normal pigs. To confirm whether KR-32 affects those of enterotoxigenic Escherichia coli (ETEC) K88-challenged pigs, we performed Exp. 2, in which 18 piglets (28 d old) were divided into the following 3 groups: 1) piglets orally challenged with 1 × 1010 cfu ETEC K88 on day 1 followed by an i.p. injection of 0.6 mg/kg KR-32 (K88 + APK); 2) piglets orally challenged with 1 × 1010 cfu ETEC K88 on day 1 followed by an i.p. injection of an equivalent volume (1 mL) of PBS (K88); and 3) piglets with an oral administration of fresh Luria-Bertani broth (50 mL) followed by an i.p. injection of an equivalent volume of PBS (CON-2). Results showed that ETEC K88 challenge led to poor ADFI, ADG, and G:F in piglets; decreased ATTD of feed nutrients, especially CP and ether extract (EE); and intestinal morphology disorder. After i.p. injection of KR-32, ADG and ATTD of CP and EE were greatly increased, G:F was significantly reduced (P < 0.05), and, especially, ATTD of EE returned to a normal level compared with group CON-2. Fatty acid absorption also highly increased after KR-32 injection. Then we focused on fat digestion and fatty acid uptake. The pH in the intestine and pancreas lipase showed no difference among the 3 treatment groups, whereas fatty acid transporter protein 4 (FATP4) expression was remarkably improved (P < 0.05) and the epithelial barrier was recovered after i.p. injection of KR-32. In conclusion, KR-32, given to ETEC K88-challenged piglets, improved growth performance, ATTD of EE, fatty acid absorption, and intestinal morphology, which indicated that KR-32 was likely to improve the expression of FATP4 and by repairing the epithelial barrier, thereby alleviating fatty acid malabsorption.


Assuntos
Anti-Infecciosos/farmacologia , Escherichia coli Enterotoxigênica/efeitos dos fármacos , Infecções por Escherichia coli/veterinária , Proteínas de Transporte de Ácido Graxo/genética , Ácidos Graxos/metabolismo , Doenças dos Suínos/tratamento farmacológico , Animais , Digestão/efeitos dos fármacos , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/microbiologia , Infecções por Escherichia coli/patologia , Proteínas de Transporte de Ácido Graxo/efeitos dos fármacos , Proteínas de Transporte de Ácido Graxo/metabolismo , Ácidos Graxos/sangue , Fezes/microbiologia , Feminino , Absorção Intestinal/efeitos dos fármacos , Intestinos/efeitos dos fármacos , Intestinos/ultraestrutura , Peptídeos/farmacologia , Distribuição Aleatória , Suínos , Doenças dos Suínos/microbiologia , Doenças dos Suínos/patologia , Desmame
4.
Int J Med Sci ; 16(3): 366-375, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30911270

RESUMO

Long-chain fatty acids are the most abundant fatty acids and are essential for various physiological processes. Translocation of long-chain fatty acids across cell membrane is dependent on transport proteins. Solute carrier family 27 member 6 (SLC27A6) is a transport protein which mediates long-chain fatty acid uptake. The bioinformatic analysis revealed that the expression of SLC27A6 in non-tumoral breast tissue was higher than that in tumoral breast cancer in clinic samples. When SLC27A6 expression in non-tumorigenic cell H184B5F5/M10 was repressed, the fatty acids uptake capacity and cell proliferation was inhibited, and cell cycle was delayed. The protein expression of cell cycle regulators including cell division protein kinase 4 (CDK4), CDK6, and cyclin D1 was significantly decreased in SLC27A6-silenced H184B5F5/M10. By contrast, relatively low SLC27A6 expression in tumorigenic breast cancer cell Hs578T when compared to H184B5F5/M10. Repressing SLC27A6 expression did not affect these phenotypes in Hs578T. The interaction network of SLC27A6 was further investigated via STRING database. The function of these SLC27A6-associated proteins mainly involved in lipid biosynthesis, fatty acid metabolic process, and fatty acid transport. In conclusion, this study reveals inverse correlation between SLC27A6 expression and tumoral tissues and provides a new insight into SLC27A6-mediated cell growth and cell cycle regulation in non-tumorigenic breast cells.


Assuntos
Neoplasias da Mama/metabolismo , Proteínas de Transporte de Ácido Graxo/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/mortalidade , Ciclo Celular/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Proteínas de Transporte de Ácido Graxo/genética , Ácidos Graxos/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Glândulas Mamárias Humanas/citologia , Mapas de Interação de Proteínas
5.
Food Funct ; 10(2): 1049-1061, 2019 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-30706921

RESUMO

The present study was designed to explore the neuroprotective effects of docosahexaenoic acid (DHA) and/or vitamin E (VE) in vitro. The PC12 cells were pretreated with DHA and/or VE for 4 h, followed by 50 µmol L-1 Aß25-35 treatments for another 48 h. The cells were then collected and used for the measurements of oxidative stress parameters. Real time-PCR and western blot were applied to measure fatty acid transporters, Nrf2 and its downstream antioxidant targets' gene and protein expression. Our results indicated that the Aß25-35 treatment inhibited cellular growth, increased intracellular ROS generation and decreased the mitochondrial membrane potential. The Aß25-35 treatment decreased the total antioxidant capacity (T-AOC), whereas it increased the MDA levels in neuron cells. Pretreatment of cells with VE or DHA could antagonize the Aß25-35-mediated cell growth inhibition and mitochondrial membrane potential decline. Activation of the Nrf2 signaling pathway and regulation of CD36, SRB1 and FABP5 expression were observed in DHA- and DHA + VE-pretreated cells. Our results indicated a synergistic effect of DHA and VE in antagonizing the oxidative damage caused by Aß25-35 in the PC12 cells. The results of the present study will shed light on the application of nutritional intervention for DHA and VE in preventing neuronal damage-related diseases.


Assuntos
Peptídeos beta-Amiloides/toxicidade , Ácidos Docosa-Hexaenoicos/farmacologia , Fator 2 Relacionado a NF-E2/metabolismo , Neurônios/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Fragmentos de Peptídeos/toxicidade , Vitamina E/farmacologia , Animais , Antígenos CD36/genética , Antígenos CD36/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Ácidos Docosa-Hexaenoicos/administração & dosagem , Proteínas do Olho/genética , Proteínas do Olho/metabolismo , Proteínas de Transporte de Ácido Graxo/genética , Proteínas de Transporte de Ácido Graxo/metabolismo , Proteínas de Ligação a Ácido Graxo/genética , Proteínas de Ligação a Ácido Graxo/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/genética , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Células PC12 , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Espécies Reativas de Oxigênio , Receptores Depuradores Classe B/genética , Receptores Depuradores Classe B/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Vitamina E/administração & dosagem
6.
Biol Pharm Bull ; 41(9): 1384-1392, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30175775

RESUMO

Docosahexaenoic acid (DHA, 22 : 6) is an essential omega-3 long-chain polyunsaturated fatty acid that plays a pivotal role in vision. The purpose of this study was to clarify the cellular uptake and binding processes of free and protein-bound unesterified DHA in retinal pigment epithelial cell (RPE) line ARPE-19 as a model of the human outer blood-retinal barrier and isolated porcine RPE cell fractions. Uptake of free [14C]DHA by ARPE-19 cells was saturable with a Michaelis-Menten constant of 283 µM, and was significantly inhibited by eicosapentaenoic acid, arachidonic acid, and linoleic acid, but not by oleic acid. Further, the uptakes of [14C]DHA associated with retinol-binding protein ([14C]DHA-RBP), [14C]DHA associated with low-density lipoprotein ([14C]DHA-LDL) and [14C]DHA associated with bovine serum albumin ([14C]DHA-BSA) in ARPE-19 cells increased time-dependently at 37°C, and were significantly reduced at 4°C, suggesting the involvement of energy-dependent transport processes. [14C]DHA-LDL uptake by ARPE-19 cells was significantly inhibited by excess unlabeled LDL, but not by an inhibitor of scavenger receptor B type I. Fatty acid transport protein (FATP) 2 and 4 mRNAs were expressed in ARPE-19 cells, and [14C]DHA uptake was observed in FATP2- and FATP4-expressing Xenopus oocytes. Photo-reactive crosslinking and mass spectrometry analyses identified 65-kDa retinal pigment epithelium-specific protein (RPE65) as a DHA-binding protein in porcine RPE cell membrane fractions. Thus, RPE cells possess multiple cellular transport/binding processes for unesterified DHA, involving at least partly FATP2, FATP4, LDL, RBP, and RPE65.


Assuntos
Barreira Hematorretiniana/metabolismo , Ácidos Docosa-Hexaenoicos/farmacologia , Células Epiteliais/metabolismo , Epitélio Pigmentado da Retina/metabolismo , Animais , Transporte Biológico , Linhagem Celular , Proteínas de Transporte de Ácido Graxo/genética , Proteínas de Transporte de Ácido Graxo/metabolismo , Humanos , Oócitos/metabolismo , Suínos , Xenopus laevis
7.
Cell Physiol Biochem ; 48(2): 556-568, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30021212

RESUMO

BACKGROUND/AIMS: Brown adipose tissue (BAT) is critical for mammals' survival in the cold environment. BAT-dependent non-shivering thermogenesis is attributed to uncoupling protein 1 (UCP1)'s disengagement of oxidative phosphorylation from ATP synthesis and dissipates energy as heat. Thus individuals with a substantial amount of BAT are better equipped during cold stress and less likely to become obese. Recently, our laboratory has shown pig adipocytes have no UCP1 protein. The inability of newborn piglets to generate heat contributed to its high death rate. Repairing the genetic defect of UCP1 in pig adipocytes has implications in defending against cold for piglets and developing an alternative treatment for human obesity. METHODS: Q-PCR, western blotting (WB) and oxygen consumption measurement were used to enable functional UCP1 protein in preadipocytes. Immunoprecipitation (IP), chromatin immunoprecipitation (CHIP), and dual-luciferase reporter assay system were used to clarify the thermogenesis mechanism of functional UCP1. RESULTS: Only co-overexpressing mice UCP1 and pig PGC-1α increased not only the mitochondrial number but also the uncoupled respiration rate in the transfected pig adipocytes. The functional mice UCP1 increased the pig PGC-1α activity through the AMPK-SIRT1 pathway. The active form PGC-1α interacted with transcription factors Lhx8, Zic1, ERRα, and PPARα to regulate the expression of mitochondrial energy metabolism and adipocytes browning-related genes. CONCLUSION: Our data suggest a model in which pig PGC-1α and mice UCP1 work collaboratively to restore uncoupling respiration in pig preadipocytes. These results have great implications for piglet survival and developing an alternative treatment for human obesity in the future.


Assuntos
Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Proteína Desacopladora 1/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Adipócitos/citologia , Adipócitos/metabolismo , Tecido Adiposo Marrom/metabolismo , Animais , Metabolismo Energético/genética , Proteínas de Transporte de Ácido Graxo/genética , Proteínas de Transporte de Ácido Graxo/metabolismo , Camundongos , Mitocôndrias/metabolismo , Proteínas Mitocondriais/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Regiões Promotoras Genéticas , Transdução de Sinais , Sirtuína 1/metabolismo , Suínos , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteína Desacopladora 1/genética
8.
J Biotechnol ; 281: 161-167, 2018 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-30016739

RESUMO

Fatty acids have a low permeability through the cell membrane. Therefore, the intracellular biotransformation of fatty acids can be slow due to supply limitations. The effects of expression level of the fatty acid transporter FadL in Escherichia coli on the biotransformations were investigated. The enhanced expression of FadL led to 5.5-fold increase of the maximum reaction rate Vmax (i.e., 200 µmol/min per g dry cells (200 U/g dry cells)) of the recombinant E. coli expressing a hydratase of Stenotrophomonas maltophilia in the periplasm with respect to hydration of oleic acid. The FadL expression level was also critical for oxidation of 12- and 10- hydroxyoctadecanoic acid by the recombinant E. coli expressing an alcohol dehydrogenase (ADH) of Micrococcus luteus. In addition, the multistep biotransformation of ricinoleic acid into the ester (i.e., (Z)-11-(heptanoyloxy)undec-9-enoic acid) by the recombinant E. coli expressing the ADH of M. luteus and a Baeyer-Villiger monooxygenase of Pseudomonas putida KT2440 was 2-fold increased to 40 U/g dry cells with expression of FadL to an appropriate level. The FadL expression level is one of the critical factors to determine whole-cell biotransformation rates of not only long chain fatty acids but also hydroxy fatty acids. This study may contribute to whole-cell biocatalyst engineering for biotransformation of hydrophobic substances.


Assuntos
Proteínas da Membrana Bacteriana Externa/metabolismo , Membrana Celular/metabolismo , Proteínas de Escherichia coli/metabolismo , Proteínas de Transporte de Ácido Graxo/metabolismo , Ácidos Graxos/metabolismo , Álcool Desidrogenase/genética , Bactérias/genética , Bactérias/metabolismo , Proteínas da Membrana Bacteriana Externa/genética , Biotransformação , Proteínas de Escherichia coli/genética , Proteínas de Transporte de Ácido Graxo/genética , Hidroliases/genética , Oxigenases de Função Mista/genética , Ácido Oleico/metabolismo
9.
Nutrients ; 10(2)2018 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-29462922

RESUMO

Adolescent pregnancy increases risk of adverse perinatal outcomes. Placental delivery of long-chain polyunsaturated fatty acids (LCPUFA) is essential for fetal growth and development. In this pilot study, we aimed to assess maternal and fetal status of fatty acids (FA) measured at birth and the expression of key genes involved in FA uptake, transport and metabolism in the placenta of fifteen adolescents and fifteen adults. FA were quantified by gas-liquid chromatography. Placental expression of FA transporters was assessed by quantitative real-time polymerase chain reaction (qRT-PCR) and peroxisome proliferator-activated receptor gamma (PPARγ) was quantified by Western Blot. Adolescents had lower docosahexaenoic acid (DHA, 22:6 n-3) and total n-3 FA levels in maternal erythrocytes and placenta, but these were not different in fetal erythrocytes. Arachidonic acid (AA, 20:4 n-6) concentration was increased in placenta but lower in fetal circulation. Plasma membrane fatty acid binding protein (FABPpm) and fatty acid transport protein (FATP) 4 mRNA expressions were not different, however FATP1, fatty acid translocase (FAT/CD36) and fatty acid binding protein 3 (FABP3) mRNA and PPARγ protein levels were decreased in placenta of adolescents. Despite significant downregulation of FATP1, CD36 and FABP3, there was only a modest decrease in LCPUFA (10%) and AA (12%) and no difference in DHA content in cord blood, suggesting that FA transfer to the fetus was partially protected by other factors in adolescents from this cohort.


Assuntos
Ácidos Graxos Insaturados/sangue , Placenta/metabolismo , Circulação Placentária , Gravidez na Adolescência , Adolescente , Adulto , Fatores Etários , Transporte Biológico , Western Blotting , Estudos Transversais , Proteínas de Transporte de Ácido Graxo/genética , Proteínas de Transporte de Ácido Graxo/metabolismo , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Humanos , PPAR gama/metabolismo , Projetos Piloto , Gravidez , Reação em Cadeia da Polimerase em Tempo Real , Adulto Jovem
10.
J Anim Physiol Anim Nutr (Berl) ; 102(1): e242-e253, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28508539

RESUMO

This study was conducted to evaluate the influence of back-fat thickness (BF), at mating of sows, on the maternal and newborn circulating lipids, expression of placental fatty acids (FA) transporters and lipid accumulation in placenta. Full-term placentas were obtained by vaginal delivery from BFI (9-14 mm; n = 37), BFII (15-19 mm; n = 43) and BFIII (20-27 mm; n = 38) sows according to BF at mating, and frozen placental sections were analysed for fat accumulation. Blood samples were collected from the sows of day 105 pregnancy and from cord blood at delivery. mRNA and protein expression levels were evaluated with real-time RT-PCR and Western blotting. Our results demonstrated that BFII females had significantly increased litter weight and placental efficiency, decreased maternal triglyceride (TG) and non-esterified fatty acids (NEFA) levels, decreased maternal IL-6, TNFα and leptin levels compared to BFIII females (p < .05). BFIII sows were associated with significantly decreased newborn TG levels, increased newborn glucose, IL-6 and TNFα levels compared to BFI or BFII sows (p < .05). BFI and BFII females had significantly decreased placental TG, NEFA and cholesterol (CHOL) contents compared to BFIII females (p < .05). Moreover, decreased CD36, FATP1, FABP4, and FABP1 mRNA and protein and FATP4 protein expression, and increased LPL activity were also observed in BFIII group compared with BFII group (p < .05). PPARγ mRNA and protein and lipogenic genes such as SREBP-1c, ACSL1, ACCα, FAS and SCD mRNA expression were downregulated or upregulated, respectively, in the placentas of BFIII sows compared to BFI or BFII sows (p < .05). Overall, this study demonstrated that there is no advantage, in terms of litter live size, litter weight and placental FA transport and metabolism, in performing the mating of sows with BF>19 mm.


Assuntos
Proteínas de Transporte de Ácido Graxo/metabolismo , Metabolismo dos Lipídeos/fisiologia , Obesidade/veterinária , Placenta/metabolismo , Doenças dos Suínos/metabolismo , Animais , Proteínas de Transporte de Ácido Graxo/genética , Ácidos Graxos/metabolismo , Feminino , Obesidade/metabolismo , Gravidez , Suínos
11.
Int Immunopharmacol ; 55: 205-215, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29272817

RESUMO

Macrophages are important cells that need to be controlled at the site of inflammation. Several factors are involved in chronic inflammation and its timely resolution. Free fatty acids drive the inflammatory response in macrophages and contribute to the vicious cycle of the inflammatory response. However, the identity of the uptake pathways of fatty acids is not fully clear in macrophages and how the inflammatory responses are regulated by the uptake of fatty acids remain poorly understood. We investigated the relationship between fatty acid transport protein (FATP) and the inflammatory response signaling pathway in macrophages as the first report. The FATP family has composed six isoforms, FATP1-6. We found that FATP1 is the most highly expressed isoform in macrophages. Forced expression of FATP1 enhanced production of inflammatory cytokines, such as TNFα and IL-6 concomitant with the increased uptake of fatty acids, increased level of ceramide, and increased phosphorylation of c-Jun N-terminal kinase (JNK). The enhancement by FATP1 was abolished by treatment with a JNK inhibitor, NF-κB inhibitor, or ceramide synthesis inhibitor. siRNA-mediated knockdown of FATP1 strongly inhibited the production of TNFα and IL-6. Similarly, an inhibitor of FATP1 inhibited the production of TNFα and IL-6. Finally, an inhibitor of FATP1 attenuated the production of inflammatory cytokines in bronchoalveolar lavage fluid in an LPS-induced acute lung injury in vivo mouse model. In summary, we propose that FATP1 is an important regulator of inflammatory response signaling in macrophages. Our findings suggest that ceramide-JNK signaling is important to terminate or sustain inflammation.


Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Proteínas de Transporte de Ácido Graxo/metabolismo , Inflamação/imunologia , Macrófagos/fisiologia , Lesão Pulmonar Aguda/induzido quimicamente , Animais , Ceramidas/metabolismo , Proteínas de Transporte de Ácido Graxo/antagonistas & inibidores , Proteínas de Transporte de Ácido Graxo/genética , Ácidos Graxos/metabolismo , Interleucina-6/metabolismo , MAP Quinase Quinase 4/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Células RAW 264.7 , RNA Interferente Pequeno/genética , Fator de Necrose Tumoral alfa/metabolismo
12.
Br J Nutr ; 118(12): 999-1009, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29198193

RESUMO

Dietary phospholipid (PL) supplementation has been shown to reduce lipid accumulation in the tissues of farmed fish; however, the mechanisms underlying this effect are largely unknown. Thus, the present study was conducted to evaluate the potential impacts of PL on hepatic lipid metabolism both in vivo and in vitro. For in vivo study, four experimental diets - low lipid and low PL diet, as control diet (LL-LP diet, containing 12 % lipid and 1·5 % PL), low-lipid and high-PL diet (containing 12 % lipid and 8 % PL), high-lipid and low-PL diet (HL-LP diet, containing 20 % lipid and 1·5 % PL) and high-lipid and high-PL diet (HL-HP diet, containing 20 % lipid and 8 % PL) - were randomly allocated to four groups of large yellow croaker (Larimichthys crocea) (three cages per group) with similar initial body weight (approximately 8 g). For in vitro study, primary hepatocytes isolated from large yellow croaker were incubated either with graded levels of phosphatidylcholine (PC) (0-250 µm) or small interfering RNA (siRNA) for CTP: choline phosphate cytidylyltranferase α (CCTα) (siRNA-CCTα). Results showed that survival was independent of dietary treatments (P>0·05). Weight gain and feed efficiency in the HL-HP group were significantly higher than in the LL-LP and HL-LP groups (P<0·05). High level of dietary PL could markedly reduce abnormal hepatic lipid accumulation induced by the HL-LP diet (P<0·05). Similarly, compared with the corresponding controls, a significant decrease/increase in lipid content was observed in primary hepatocytes incubated with PC/siRNA-CCTα (P<0·05). High level of dietary PL reversed the HL-LP diet-induced increased levels of mRNA of fatty acid uptake and lipid synthesis related genes (P<0·05). In addition, High level of dietary PL markedly down-regulated the transcript levels of fatty acid oxidation-related genes and enhanced the transcript levels of VLDL assembly-related genes regardless of dietary lipid levels (P<0·05). Compared with corresponding controls, primary hepatocytes treated with PC showed significantly higher mRNA expression of lipid synthesis and VLDL assembly-related genes and lower mRNA expression of fatty acid oxidation-related genes, with hepatocytes treated with siRNA-CCTα exhibiting the opposite trend (P<0·05). In summary, these results demonstrated that high level of dietary PL might reverse the HL-LP diet-induced abnormal lipid accumulation in the liver through inhibiting fatty acid uptake and lipid synthesis, together with promoting the lipid export at the transcriptional level. Lipid export-promoting effect of PC was confirmed by in vitro studies. The present study showed for the first time that PL or PC could influence various metabolic pathways to regulate hepatic lipid deposition in fish at least at the transcriptional level.


Assuntos
Dieta/veterinária , Metabolismo dos Lipídeos , Fígado/metabolismo , Perciformes/metabolismo , Fosfolipídeos/administração & dosagem , Ração Animal , Animais , Antígenos CD36/genética , Antígenos CD36/metabolismo , Células Cultivadas , Diacilglicerol O-Aciltransferase/genética , Diacilglicerol O-Aciltransferase/metabolismo , Ácido Graxo Sintases/genética , Ácido Graxo Sintases/metabolismo , Proteínas de Transporte de Ácido Graxo/genética , Proteínas de Transporte de Ácido Graxo/metabolismo , Proteínas de Ligação a Ácido Graxo/genética , Proteínas de Ligação a Ácido Graxo/metabolismo , Ácidos Graxos/metabolismo , Proteínas de Peixes/genética , Proteínas de Peixes/metabolismo , Hepatócitos/metabolismo , Lipase/genética , Lipase/metabolismo , Lipase Lipoproteica/genética , Lipase Lipoproteica/metabolismo , Fosfatidilcolinas/administração & dosagem , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo
13.
Epigenomics ; 9(11): 1403-1422, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28990796

RESUMO

AIM: Homocysteine (Hcy) is a sensitive marker of one-carbon metabolism. Higher Hcy levels have been associated with global DNA hypomethylation. We investigated the association between plasma Hcy and epigenome-wide DNA methylation in leukocytes. METHODS: Methylation was measured using Illumina 450 k arrays in 2035 individuals from six cohorts. Hcy-associated differentially methylated positions and regions were identified using meta-analysis. RESULTS: Three differentially methylated positions cg21607669 (SLC27A1), cg26382848 (AJUBA) and cg10701000 (KCNMA1) at chromosome 19, 14 and 10, respectively, were significantly associated with Hcy. In addition, we identified 68 Hcy-associated differentially methylated regions, the most significant of which was a 1.8-kb spanning domain (TNXB/ATF6B) at chromosome 6. CONCLUSION: We identified novel epigenetic loci associated with Hcy levels, of which specific role needs to be further validated.


Assuntos
Metilação de DNA , Epigênese Genética , Homocisteína/sangue , Leucócitos/metabolismo , Fatores de Transcrição de Zíper de Leucina Básica/genética , Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Proteínas de Transporte de Ácido Graxo/genética , Proteínas de Transporte de Ácido Graxo/metabolismo , Feminino , Estudo de Associação Genômica Ampla , Humanos , Proteínas com Domínio LIM/genética , Proteínas com Domínio LIM/metabolismo , Subunidades alfa do Canal de Potássio Ativado por Cálcio de Condutância Alta/genética , Subunidades alfa do Canal de Potássio Ativado por Cálcio de Condutância Alta/metabolismo , Masculino , Tenascina/genética , Tenascina/metabolismo
14.
Artigo em Inglês | MEDLINE | ID: mdl-28987718

RESUMO

Long-chain polyunsaturated fatty acids (LC-PUFA), mainly docosahexaenoic (DHA) and arachidonic acids (AA), are critical for adequate fetal growth and development. We investigated mRNA expression of proteins involved in hydrolysis, uptake and/or transport of fatty acids in placenta of fifteen full term normal pregnancies and eleven pregnancies complicated by intrauterine growth restriction (IUGR) with normal umbilical blood flows. The mRNA expression of LPL, FATPs (-1, -2 and -4) and FABPs (-1 and -3) was increased in IUGR placentas, however, tissue profile of LC-PUFA was not different between groups. Erythrocytes from both mothers and fetuses of the IUGR group showed lower concentrations of AA and DHA and inferior DHA/ALA ratio compared to normal pregnancies (P < 0.05). We hypothesize that reduced circulating levels of AA and DHA could up-regulate mRNA expression of placental fatty acids transporters, as a compensatory mechanism, however this failed to sustain normal LC-PUFA supply to the fetus in IUGR.


Assuntos
Eritrócitos/metabolismo , Proteínas de Transporte de Ácido Graxo/metabolismo , Ácidos Graxos/metabolismo , Retardo do Crescimento Fetal/metabolismo , Placenta/metabolismo , Adulto , Proteínas de Transporte de Ácido Graxo/genética , Proteínas de Ligação a Ácido Graxo/genética , Feminino , Retardo do Crescimento Fetal/genética , Humanos , Lipase Lipoproteica/genética , Troca Materno-Fetal , Gravidez , RNA Mensageiro/genética , Adulto Jovem
15.
Atherosclerosis ; 266: 182-189, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29035781

RESUMO

BACKGROUND AND AIMS: Altered metabolism is an important regulator of macrophage (MΦ) phenotype, which contributes to inflammatory diseases such as atherosclerosis. Broadly, pro-inflammatory, classically-activated MΦs (CAM) are glycolytic while alternatively-activated MΦs (AAM) oxidize fatty acids, although overlap exists. We previously demonstrated that MΦ fatty acid transport protein 1 (FATP1, Slc27a1) was necessary to maintain the oxidative and anti-inflammatory AAM phenotype in vivo in a model of diet-induced obesity. The aim of this study was to examine how MΦ metabolic reprogramming through FATP1 ablation affects the process of atherogenesis. We hypothesized that FATP1 limits MΦ-mediated inflammation during atherogenesis. Thus, mice lacking MΦ Fatp1 would display elevated formation of atherosclerotic lesions in a mouse model lacking the low-density lipoprotein (LDL) receptor (Ldlr-/-). METHODS: We transplanted bone marrow collected from Fatp1+/+ or Fatp1-/- mice into Ldlr-/- mice and fed chimeric mice a Western diet for 12 weeks. Body weight, blood glucose, and plasma lipids were measured. Aortic sinus and aorta lesions were quantified. Atherosclerotic plaque composition, oxidative stress, and inflammation were analyzed histologically. RESULTS: Compared to Fatp1+/+Ldlr-/- mice, Fatp1-/-Ldlr-/- mice exhibited significantly larger lesion area and elevated oxidative stress and inflammation in the atherosclerotic plaque. Macrophage and smooth muscle cell content did not differ by Fatp1 genotype. There were no significant systemic alterations in LDL, high-density lipoprotein (HDL), total cholesterol, or triacylglyceride, suggesting that the effect was local to the cells of the vessel microenvironment in a Fatp1-dependent manner. CONCLUSIONS: MΦ Fatp1 limits atherogenesis and may be a viable target to metabolically reprogram MΦs.


Assuntos
Aorta/metabolismo , Doenças da Aorta/metabolismo , Aterosclerose/metabolismo , Proteínas de Transporte de Ácido Graxo/deficiência , Ativação de Macrófagos , Macrófagos Peritoneais/metabolismo , Placa Aterosclerótica , Receptores de LDL/deficiência , Animais , Aorta/patologia , Doenças da Aorta/genética , Doenças da Aorta/patologia , Aterosclerose/genética , Aterosclerose/patologia , Glicemia/metabolismo , Transplante de Medula Óssea , Células Cultivadas , Microambiente Celular , Modelos Animais de Doenças , Proteínas de Transporte de Ácido Graxo/genética , Predisposição Genética para Doença , Inflamação/genética , Inflamação/metabolismo , Inflamação/patologia , Lipídeos/sangue , Masculino , Camundongos Knockout , Estresse Oxidativo , Fenótipo , Receptores de LDL/genética , Quimeras de Transplante
16.
Nutrients ; 9(7)2017 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-28696376

RESUMO

The aims of the present study were to analyze the effect of resveratrol on liver steatosis in obese rats, to compare the effects induced by resveratrol and energy restriction and to research potential additive effects. Rats were initially fed a high-fat high-sucrose diet for six weeks and then allocated in four experimental groups fed a standard diet: a control group, a resveratrol-treated group, an energy restricted group and a group submitted to energy restriction and treated with resveratrol. We measured liver triacylglycerols, transaminases, FAS, MTP, CPT1a, CS, COX, SDH and ATP synthase activities, FATP2/FATP5, DGAT2, PPARα, SIRT1, UCP2 protein expressions, ACC and AMPK phosphorylation and PGC1α deacetylation. Resveratrol reduced triacylglycerols compared with the controls, although this reduction was lower than that induced by energy restriction. The mechanisms of action were different. Both decreased protein expression of fatty acid transporters, thus suggesting reduced fatty acid uptake from blood stream and liver triacylglycerol delivery, but only energy restriction reduced the assembly. These results show that resveratrol is useful for liver steatosis treatment within a balanced diet, although its effectiveness is lower than that of energy restriction. However, resveratrol is unable to increase the reduction in triacylglycerol content induced by energy restriction.


Assuntos
Restrição Calórica , Fígado Gorduroso/tratamento farmacológico , Estilbenos/farmacologia , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Acetil-CoA Carboxilase/genética , Acetil-CoA Carboxilase/metabolismo , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Coenzima A Ligases/genética , Coenzima A Ligases/metabolismo , Diacilglicerol O-Aciltransferase/genética , Diacilglicerol O-Aciltransferase/metabolismo , Dieta Hiperlipídica/efeitos adversos , Proteínas de Transporte de Ácido Graxo/genética , Proteínas de Transporte de Ácido Graxo/metabolismo , Ácidos Graxos/administração & dosagem , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Tamanho do Órgão/efeitos dos fármacos , PPAR alfa/genética , PPAR alfa/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Ratos , Ratos Wistar , Resveratrol , Sirtuína 1/genética , Sirtuína 1/metabolismo , Triglicerídeos/sangue , Proteína Desacopladora 2/genética , Proteína Desacopladora 2/metabolismo
17.
J Clin Res Pediatr Endocrinol ; 9(4): 300-307, 2017 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-28588000

RESUMO

OBJECTIVE: To explore the effects of maternal high-fat (HF) diet-induced obesity on fetal growth and the expression of placental nutrient transporters. METHODS: Maternal obesity was established in rats by 8 weeks of pre-pregnancy fed HF diet, while rats in the control group were fed normal (CON) diet. Diet-induced obesity (DIO) rats and diet-induced obesity-resistant (DIR) rats were selected according to body weight gain over this period. After copulation, the CON rats were divided into two groups: switched to HF diet (CON-HF group) or maintained on the CON diet (CON-CON group). The DIO rats and DIR rats were maintained on the HF diet throughout pregnancy. Pregnant rats were euthanized at day 21 gestation, fetal and placental weights were recorded, and placental tissue was collected. Reverse transcription-polymerase chain reaction was used to determine mRNA expression of placental nutrient transporters. Protein expression was determined by Western blot. RESULTS: Average fetal weight of DIO dams was reduced by 6.9%, and the placentas of CON-HF and DIO dams were significantly heavier than the placentas of CON-CON and DIR dams at day 21 of gestation (p<0.05). The fetal/placental weight ratio of DIO dams was significantly reduced compared with the fetal/placental weight ratio of CON-CON dams (p<0.05). The mRNA expression of GLUT-1 and SNAT-2 were not significantly different between groups. The mRNA and protein expression levels of CD36, FATP-1, and FATP-4 in DIO dams were decreased significantly (p<0.05). CONCLUSION: Maternal obesity induced by a HF diet led to intrauterine growth retardation and down-regulated the expression of placental fatty acid transporters.


Assuntos
Proteínas de Transporte de Ácido Graxo/genética , Desenvolvimento Fetal/fisiologia , Obesidade , Placenta/metabolismo , Complicações na Gravidez , Animais , Dieta Hiperlipídica , Proteínas de Transporte de Ácido Graxo/metabolismo , Ácidos Graxos/metabolismo , Feminino , Masculino , Fenômenos Fisiológicos da Nutrição Materna , Obesidade/genética , Obesidade/fisiopatologia , Gravidez , Complicações na Gravidez/genética , Complicações na Gravidez/fisiopatologia , Ratos , Ratos Sprague-Dawley
18.
J Endocrinol ; 233(3): 329-340, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28522731

RESUMO

Intramuscular accumulation of bioactive lipids leads to insulin resistance and type 2 diabetes (T2D). There is lack of consensus concerning which of the lipid mediators has the greatest impact on muscle insulin action in vivo Our aim was to elucidate the effects of high-fat diet (HFD) and metformin (Met) on skeletal muscle bioactive lipid accumulation and insulin resistance (IR) in rats. We employed a [U-13C]palmitate isotope tracer and mass spectrometry to measure the content and fractional synthesis rate (FSR) of intramuscular long-chain acyl-CoA (LCACoA), diacylglycerols (DAG) and ceramide (Cer). Eight weeks of HFD-induced intramuscular accumulation of LCACoA, DAG and Cer accompanied by both systemic and skeletal muscle IR. Metformin treatment improved insulin sensitivity at both systemic and muscular level by the augmentation of Akt/PKB and AS160 phosphorylation and decreased the content of DAG and Cer and their respective FSR. Principal component analysis (PCA) of lipid variables revealed that altered skeletal muscle IR was associated with lipid species containing 18-carbon acyl-chain, especially with C18:0-Cer, C18:1-Cer, 18:0/18:2-DAG and 18:2/18:2-DAG, but not palmitate-derived lipids. It is concluded that the insulin-sensitizing action of metformin in skeletal muscle is associated with decreased 18-carbon acyl-chain-derived bioactive lipids.


Assuntos
Resistência à Insulina/fisiologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Metformina/farmacologia , Músculo Esquelético/efeitos dos fármacos , Animais , Coenzima A Ligases/genética , Coenzima A Ligases/metabolismo , Dieta Hiperlipídica/efeitos adversos , Proteínas de Transporte de Ácido Graxo/genética , Proteínas de Transporte de Ácido Graxo/metabolismo , Ácidos Graxos não Esterificados/sangue , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/fisiologia , Masculino , Metformina/administração & dosagem , Músculo Esquelético/metabolismo , Ratos , Ratos Wistar
19.
Protein Expr Purif ; 134: 72-81, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28389350

RESUMO

The trematode Schistosoma mansoni Sm14 antigen was expressed in the yeast Pichia pastoris and secreted into the culture medium at yields of approximately 250 mg L-1. Sm14 belongs to a family of fatty-acid binding proteins and appears to play an important role in uptake, transport, and compartmentalization of lipids in S. mansoni and it is a potential vaccine candidate in both humans and domesticated animals. The Sm14 gene was codon-optimized for expression in P. pastoris, and placed under transcription of the strong methanol inducible AOX1 promoter. Mut+ transformants were selected and used in fed-batch cultivation using a 2.5L fermenter equipped with an on-line methanol control system in order to maintain constant methanol levels during induction. Optimal conditions for the expression of Sm14 by P. pastoris were found to be: dissolved oxygen at 40%, temperature of 25 °C, pH 5.0, and a constant methanol concentration of 1 gL-1. Our results show that a correctly processed Sm14 was secreted into the culture medium at levels of approximately 250  mg L-1. Sm14 from clarified culture medium was purified using a two-step procedure: anion-exchange chromatography followed by hydrophobic interaction chromatography, resulting in >95% purity with a final yield of 40% from the starting cell culture medium. This product has been tested in preliminary clinical trials and shown to elicit an antibody response with no adverse reactions.


Assuntos
Antígenos de Helmintos , Proteínas de Transporte de Ácido Graxo , Expressão Gênica , Proteínas de Helminto , Pichia/metabolismo , Schistosoma mansoni/genética , Vacinas , Animais , Antígenos de Helmintos/biossíntese , Antígenos de Helmintos/genética , Antígenos de Helmintos/imunologia , Antígenos de Helmintos/isolamento & purificação , Proteínas de Transporte de Ácido Graxo/biossíntese , Proteínas de Transporte de Ácido Graxo/genética , Proteínas de Transporte de Ácido Graxo/imunologia , Proteínas de Transporte de Ácido Graxo/isolamento & purificação , Proteínas de Helminto/biossíntese , Proteínas de Helminto/genética , Proteínas de Helminto/imunologia , Proteínas de Helminto/isolamento & purificação , Humanos , Pichia/genética , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/isolamento & purificação , Schistosoma mansoni/imunologia , Vacinas/biossíntese , Vacinas/genética , Vacinas/imunologia , Vacinas/isolamento & purificação
20.
Environ Health ; 16(1): 35, 2017 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-28381288

RESUMO

BACKGROUND: Prenatal urinary concentrations of phthalates in women participants in an urban birth cohort were associated with outcomes in their children related to neurodevelopment, autoimmune disease risk, and fat mass at 3,5,7, and 8 years of life. Placental biomarkers and outcomes at birth may offer biologic insight into these associations. This is the first study to address these associations with candidate genes from the phthalate and placenta literature, accounting for sex differences, and using absolute quantitation methods for mRNA levels. METHODS: We measured candidate mRNAs in 180 placentas sampled at birth (HSD17B1, AHR, CGA, CYP19A1, SLC27A4, PTGS2, PPARG, CYP11A1) by quantitative PCR and an absolute standard curve. We estimated associations of loge mRNA with quartiles of urinary phthalate monoesters using linear mixed models. Phthalate metabolites (N = 358) and mRNAs (N = 180) were transformed to a z-score and modeled as independent, correlated vectors in relation to large for gestational age (LGA) and gestational diabetes mellitus (GDM). RESULTS: CGA was associated with 4 out of 6 urinary phthalates. CGA was 2.0 loge units lower at the 3rd vs. 1st quartile of mono-n-butyl phthalate (MnBP) (95% confidence interval (CI): -3.5, -0.5) in male placentas, but 0.6 loge units higher (95% CI: -0.8, 1.9) in female placentas (sex interaction p = 0.01). There was an inverse association of MnBP with PPARG in male placentas (-1.1 loge units at highest vs. lowest quartile, 95% CI: -2.0, -0.1). CY19A1, CYP11A1, CGA were associated with one or more of the following in a sex-specific manner: monobenzyl phthalate (MBzP), MnBP, mono-iso-butyl phthalate (MiBP). These 3 mRNAs were lower by 1.4-fold (95% CI: -2.4, -1.0) in male GDM placentas vs. female and non-GDM placentas (p-value for interaction = 0.04). The metabolites MnBP/MiBP were 16% higher (95% CI: 0, 22) in GDM pregnancies. CONCLUSIONS: Prenatal concentrations of certain phthalates and outcomes at birth were modestly associated with molecular changes in fetal placental tissue during pregnancy. Associations were stronger in male vs. female placentas, and associations with MnBP and MiBP were stronger than other metabolites. Placental mRNAs are being pursued further as potential mediators of exposure-induced risks to the health of the child.


Assuntos
Poluentes Ambientais/urina , Exposição Materna , Ácidos Ftálicos/urina , Placenta/metabolismo , RNA Mensageiro/metabolismo , Adulto , Aromatase/genética , Enzima de Clivagem da Cadeia Lateral do Colesterol/genética , Estradiol Desidrogenases/genética , Proteínas de Transporte de Ácido Graxo/genética , Feminino , Expressão Gênica , Subunidade alfa de Hormônios Glicoproteicos/genética , Humanos , Masculino , PPAR gama/genética , Gravidez , Receptores de Hidrocarboneto Arílico/genética , Caracteres Sexuais , População Urbana , Adulto Jovem
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