scholarly journals Microarray analysis of hepatic genes differentially expressed in the presence of the unsaponifiable fraction of olive oil in apolipoprotein E-deficient mice

2007 ◽  
Vol 97 (4) ◽  
pp. 628-638 ◽  
Author(s):  
Sergio Acín ◽  
María A. Navarro ◽  
Javier S. Perona ◽  
Joaquín C. Surra ◽  
Natalia Guillen ◽  
...  

The hypothesis that the unsaponifiable fraction of olive oil dramatically influences hepatic gene expression was tested in mice. Two olive oils, obtained from the same olive cultivar but by different technological procedures, were characterized to show that they differed mainly in terms of the composition/quantity of this unsaponifiable fraction. Using DNA microarrays, hepatic gene expression was analysed in apoE-deficient mice fed one of two isoenergetic, isonitrogenous diets containing either 10 % (w/w) olive oil or unsaponifiable fraction-enriched olive oil. To provide an initial screening of potential candidate genes involved in a differential response, only genes with remarkably modified expression (signal log2 ratio >3 or < − 3) were further considered. The eleven genes fulfilling these prerequisites were confirmed by quantitative RT–PCR, and then analysed in apoE-deficient mice with a C57BL/6J genetic background. Orosomucoid and serum amyloid A2 were upregulated (to variable extents depending on the genetic background) in the absence of hepatic steatosis and inflammation. Fabp5 and Mt2 were also strongly upregulated. Several proteases were highly suppressed by the unsaponifiable-enriched olive diet, independent of the genetic background. The findings indicate that change in the expression of these genes is a good marker of the intake of the unsaponifiable fraction of olive oil. The results highlight the important biological effects of the unsaponifiable fraction of olive oil. The term ‘monounsaturated fatty acid-enriched oil’ no longer appears appropriate for describing all the oils to which it is currently applied since it does not adequately reflect that they have different biological effects.

2009 ◽  
Vol 37 (3) ◽  
pp. 187-198 ◽  
Author(s):  
Natalia Guillén ◽  
María A. Navarro ◽  
Carmen Arnal ◽  
Enda Noone ◽  
José M. Arbonés-Mainar ◽  
...  

Trans-10, cis-12-conjugated linoleic acid (CLA)-enriched diets promote fatty liver in mice, while cis-9, trans-11-CLA ameliorates this effect, suggesting regulation of multiple genes. To test this hypothesis, apoE-deficient mice were fed a Western-type diet enriched with linoleic acid isomers, and their hepatic gene expression was analyzed with DNA microarrays. To provide an initial screening of candidate genes, only 12 with remarkably modified expression between both CLA isomers were considered and confirmed by quantitative RT-PCR. Additionally mRNA expression of 15 genes involved in lipid metabolism was also studied. Ten genes (Fsp27, Aqp4, Cd36, Ly6d, Scd1, Hsd3b5, Syt1, Cyp7b1, and Tff3) showed significant associations among their expressions and the degree of hepatic steatosis. Their involvement was also analyzed in other models of steatosis. In hyperhomocysteinemic mice lacking Cbs gene, only Fsp27, Cd36, Scd1, Syt1, and Hsd3b5 hepatic expressions were associated with steatosis. In apoE-deficient mice consuming olive-enriched diet displaying reduction of the fatty liver, only Fsp27 and Syt1 expressions were found associated. Using this strategy, we have shown that expression of these genes is highly associated with hepatic steatosis in a genetic disease such as Cbs deficiency and in two common situations such as Western diets containing CLA isomers or a Mediterranean-type diet. Conclusion: The results highlight new processes involved in lipid handling in liver and will help to understand the complex human pathology providing new proteins and new strategies to cope with hepatic steatosis.


2017 ◽  
pp. 67-74 ◽  
Author(s):  
Masashi Morita ◽  
Ayako Honda ◽  
Akira Kobayashi ◽  
Yuichi Watanabe ◽  
Shiro Watanabe ◽  
...  

2012 ◽  
Vol 44 (22) ◽  
pp. 1073-1089 ◽  
Author(s):  
M. J. J. Ronis ◽  
J. N. Baumgardner ◽  
J. C. Marecki ◽  
L. Hennings ◽  
X. Wu ◽  
...  

To determine if dietary fat composition affects the progression of nonalcoholic fatty liver disease (NAFLD), we overfed male Sprague-Dawley rats low (5%) or high (70%) fat diets with different fat sources: olive oil (OO), corn oil (CO), or echium oil (EO), with total enteral nutrition (TEN) for 21 days. Overfeeding of the 5% CO or 5% EO diets resulted in less steatosis than 5% OO ( P < 0.05). Affymetrix array analysis revealed significant differences in hepatic gene expression signatures associated with greater fatty acid synthesis, ChREBP, and SREBP-1c signaling and increased fatty acid transport ( P < 0.05) in the 5% OO compared with 5% CO group. The OO groups had macrosteatosis, but no evidence of oxidative stress or necrosis. The 70% CO and 70% EO groups had a mixture of micro- and macrosteatosis or only microsteatosis, respectively; increased oxidative stress; and increased necrotic injury relative to their respective 5% groups ( P < 0.05). Oxidative stress and necrosis correlated with increasing peroxidizability of the accumulated triglycerides. Affymetrix array analysis comparing the 70% OO and 70% CO groups revealed increased antioxidant pathways and lower expression of genes linked to inflammation and fibrosis in the 70% OO group. A second study in which 70% OO diet was overfed for 50 days produced no evidence of progression of injury beyond simple steatosis. These data suggest that dietary fat type strongly influences the progression of NAFLD and that a Mediterranean diet high in olive oil may reduce the risk of NAFLD progressing to nonalcoholic steatohepatitis.


2012 ◽  
Vol 44 (14) ◽  
pp. 702-716 ◽  
Author(s):  
Mario Nuño-Ayala ◽  
Natalia Guillén ◽  
Carmen Arnal ◽  
José M. Lou-Bonafonte ◽  
Alba de Martino ◽  
...  

Hyperhomocysteinemia has been reported in human reproduction as a risk factor for early pregnancy loss, preeclampsia, and congenital birth defects like spina bifida. Female infertility was also observed in cystathionine beta synthase-deficient mice ( Cbs-KO) as an animal model for severe hyperhomocysteinemia. The aim for the present research was to elucidate the time-point of pregnancy loss and to pinpoint gene and cellular changes involved in the underlying pathological mechanism. By mating 90-day-old wild-type and Cbs-KO female mice with their homologous male partners, we found that pregnancy loss in Cbs-KO occurred between the 8th and 12th gestation day during placenta formation. DNA microarrays were carried out on uterus from implantation and interimplantation samples obtained on day 8. The results allowed us to select genes potentially involved in embryo death; these were individually confirmed by RT-qPCR, and their expressions were also followed throughout pregnancy. We found that changes in expression of Calb1, Ttr, Expi, Inmt, Spink3, Rpgrip1, Krt15, Mt-4, Gzmc, Gzmb, Tdo2, and Afp were important for pregnancy success, since a different regulation in Cbs-KO mice was found. Also, differences in relationships among selected genes were observed, indicating a dysregulation of these genes in Cbs-KO females. In conclusion, our data provide more information on the gene expression cascade and its timely regulated process required for a successful pregnancy. In addition, we unveil new potential avenues to explore further investigations in pregnancy loss.


2006 ◽  
Vol 34 (4) ◽  
pp. 256-265 ◽  
Author(s):  
W SATO ◽  
Y HORIE ◽  
E KATAOKA ◽  
S OHSHIMA ◽  
T DOHMEN ◽  
...  

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Keisuke Ikegami ◽  
Kazumasa Saigoh ◽  
Atsuko Fujioka ◽  
Mamoru Nagano ◽  
Ken Kitajima ◽  
...  

Abstract ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 2 (ST8SIA2) synthesizes polysialic acid (PSA), which is essential for brain development. Although previous studies reported that St8sia2-deficient mice that have a mixed 129 and C57BL/6 (B6) genetic background showed mild and variable phenotypes, the reasons for this remain unknown. We hypothesized that this phenotypic difference is caused by diversity in the expression or function of flanking genes of St8sia2. A genomic polymorphism and gene expression analysis in the flanking region revealed reduced expression of insulin-like growth factor 1 receptor (Igf1r) on the B6 background than on that of the 129 strain. This observation, along with the finding that administration of an IGF1R agonist during pregnancy increased litter size, suggests that the decreased expression of Igf1r associated with ST8SIA2 deficiency caused lethality. This study demonstrates the importance of gene expression level in the flanking regions of a targeted null allele having an effect on phenotype.


2014 ◽  
Vol 84 (3-4) ◽  
pp. 0183-0195 ◽  
Author(s):  
Takashi Nakamura ◽  
Tomoya Takeda ◽  
Yoshihiko Tokuji

The common water-soluble organic germanium compound poly-trans-[(2-carboxyethyl) germasesquioxane] (Ge-132) exhibits activities related to immune responses and antioxidant induction. In this study, we evaluated the antioxidative effect of dietary Ge-132 in the plasma of mice. Male ICR mice (seven mice per group) received an AIN-76 diet with 0.05 % Ge-132; three groups received the Ge-132-containing diet for 0, 1 or 4 days. The plasma alpha-tocopherol (α-tocopherol) concentration increased from 6.85 to 9.60 μg/ml after 4 days of Ge-132 intake (p < 0.05). We evaluated the changes in hepatic gene expression related to antioxidative activity as well as in the entire expression profile after one day of Ge-132 intake, using DNA microarray technology. We identified 1,220 genes with altered expression levels greater than 1.5-fold (increased or decreased) as a result of Ge-132 intake, and α-tocopherol transfer protein (Ttpa) gene expression was increased 1.62-fold. Immune activation was identified as the category with the most changes (containing 60 Gene Ontology (GO) term biological processes (BPs), 41 genes) via functional clustering analysis of altered gene expression. Ge-132 affected genes in clusters related to ATP production (22 GO term BPs, 21 genes), lipid metabolism (4 GO term BPs, 38 genes) and apoptosis (5 GO term BPs). Many GO term BPs containing these categories were significantly affected by the Ge-132 intake. Oral Ge-132 intake may therefore have increased plasma α-tocopherol levels by up-regulating α-tocopherol transfer protein (Ttpa) gene expression.


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