scholarly journals Influence of virgin coconut oil-enriched diet on the transcriptional regulation of fatty acid synthesis and oxidation in rats – a comparative study

2014 ◽  
Vol 111 (10) ◽  
pp. 1782-1790 ◽  
Author(s):  
Sakunthala Arunima ◽  
Thankappan Rajamohan
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Mrna Expression ◽  
Fatty Acid Synthase ◽  
Target Genes ◽  
De Novo ◽  
Regulatory Element ◽  
Coconut Oil ◽  
Acid Oxidation ◽  
Virgin Coconut Oil

The present study was carried out to evaluate the effects of virgin coconut oil (VCO) compared with copra oil, olive oil and sunflower-seed oil on the synthesis and oxidation of fatty acids and the molecular regulation of fatty acid metabolism in normal rats. Male Sprague–Dawley rats were fed the test oils at 8 % for 45 d along with a synthetic diet. Dietary supplementation of VCO decreased tissue lipid levels and reduced the activity of the enzymes involved in lipogenesis, namely acyl CoA carboxylase and fatty acid synthase (FAS) (P< 0·05). Moreover, VCO significantly (P< 0·05) reduced thede novosynthesis of fatty acids by down-regulating the mRNA expression of FAS and its transcription factor, sterol regulatory element-binding protein-1c, compared with the other oils. VCO significantly (P< 0·05) increased the mitochondrial and peroxisomal β-oxidation of fatty acids, which was evident from the increased activities of carnitine palmitoyl transferase I, acyl CoA oxidase and the enzymes involved in mitochondrial β-oxidation; this was accomplished by up-regulating the mRNA expression of PPARα and its target genes involved in fatty acid oxidation. In conclusion, the present results confirmed that supplementation of VCO has beneficial effects on lipid parameters by reducing lipogenesis and enhancing the rate of fatty acid catabolism; this effect was mediated at least in part via PPARα-dependent pathways. Thus, dietary VCO reduces the risk for CHD by beneficially modulating the synthesis and degradation of fatty acids.

Regulation of the SREBP transcription factors by mTORC1

2011 ◽  
Vol 39 (2) ◽  
pp. 495-499 ◽  
Author(s):  
Caroline A. Lewis ◽  
Beatrice Griffiths ◽  
Claudio R. Santos ◽  
Mario Pende ◽  
Almut Schulze
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Synthase ◽  
Target Genes ◽  
De Novo ◽  
Regulatory Element ◽  
Cholesterol Biosynthesis ◽  
Mammalian Target Of Rapamycin ◽  
Lipid Biosynthesis ◽  
De Novo Lipogenesis ◽  
Genes Encoding

In recent years several reports have linked mTORC1 (mammalian target of rapamycin complex 1) to lipogenesis via the SREBPs (sterol-regulatory-element-binding proteins). SREBPs regulate the expression of genes encoding enzymes required for fatty acid and cholesterol biosynthesis. Lipid metabolism is perturbed in some diseases and SREBP target genes, such as FASN (fatty acid synthase), have been shown to be up-regulated in some cancers. We have previously shown that mTORC1 plays a role in SREBP activation and Akt/PKB (protein kinase B)-dependent de novo lipogenesis. Our findings suggest that mTORC1 plays a crucial role in the activation of SREBP and that the activation of lipid biosynthesis through the induction of SREBP could be part of a regulatory pathway that co-ordinates protein and lipid biosynthesis during cell growth. In the present paper, we discuss the increasing amount of data supporting the potential mechanisms of mTORC1-dependent activation of SREBP as well as the implications of this signalling pathway in cancer.

scholarly journals A role for PPARα in the control of SREBP activity and lipid synthesis in the liver

2005 ◽  
Vol 389 (2) ◽  
pp. 413-421 ◽  
Author(s):  
Brian L. Knight ◽  
Abdel Hebbachi ◽  
David Hauton ◽  
Anna-Marie Brown ◽  
David Wiggins ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Cholesterol Synthesis ◽  
Fatty Acid Synthase ◽  
De Novo ◽  
Regulatory Element ◽  
Active Form ◽  
Dietary Cholesterol ◽  
Acid Oxidation ◽  
Mrna Levels ◽  
Hepatic Expression

Inclusion of the PPARα (peroxisome-proliferator-activated receptor α) activator WY 14,643 in the diet of normal mice stimulated the hepatic expression of not only genes of the fatty acid oxidation pathway, but also those of the de novo lipid synthetic pathways. Induction of fatty acid synthase mRNA by WY 14,643 was greater during the light phase of the diurnal cycle, when food intake was low and PPARα expression was high. Hepatic fatty acid pathway flux in vivo showed a similar pattern of increases. The abundance of mRNAs for genes involved in hepatic cholesterol synthesis was also increased by WY 14,643, but was associated with a decrease in cholesterogenic carbon flux. None of these changes were apparent in PPARα-null mice. Mice of both genotypes showed the expected decreases in 3-hydroxy-3-methylglutaryl-CoA reductase mRNA levels and cholesterol synthesis in response to an increase in dietary cholesterol. The increase in fatty acid synthesis due to WY 14,643 was not mediated by increased expression of SREBP-1c (sterol regulatory element binding protein-1c) mRNA, but by an increase in cleavage of the protein to the active form. An accompanying rise in stearoyl-CoA desaturase mRNA expression suggested that the increase in lipogenesis could have resulted from an alteration in membrane fatty acid composition that influenced SREBP activation.

scholarly journals Mogroside V Protects against Hepatic Steatosis in Mice on a High-Fat Diet and LO2 Cells Treated with Free Fatty Acids via AMPK Activation

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Linghuan Li ◽  
Wanfang Zheng ◽  
Can Wang ◽  
Jiameng Qi ◽  
Hanbing Li
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Lipid Metabolism ◽  
Free Fatty Acids ◽  
Mrna Expression ◽  
Hepatic Steatosis ◽  
High Fat Diet ◽  
De Novo ◽  
Acid Oxidation ◽  
High Fat

Previous studies presented various beneficial effects of mogrosides extract from Siraitia grosvenorii, which has been included in the list of Medicine Food Homology Species in China. Mogroside V (MV) is one of the main ingredients in mogrosides extract; however, whether and how MV improves impaired lipid metabolism in the liver remains to be elucidated. Herein, we investigated the therapeutic effects of mogroside V upon hepatic steatosis in vivo and in vitro and explored the underlying mechanisms. The results showed that MV significantly ameliorated hepatic steatosis in high-fat diet- (HFD-) fed mice. Furthermore, the increased protein expression of PPAR-γ, SREBP-1, and FASN and mRNA expression of pparg, srebp1, scd1, and fasn in the liver in HFD-fed mice, which contribute to de novo lipogenesis, were dose-dependently reversed by MV treatment. Meanwhile, MV counteracted the suppressed expression of PPAR-α and CPT-1A and mRNA expression of atgl, hsl, ppara, and cpt1a, thus increasing lipolysis and fatty acid oxidation. In addition, in free fatty acids- (FFAs-) incubated LO2 cells MV downregulated de novo lipogenesis and upregulated lipolysis and fatty acid oxidation, thereby attenuating lipid accumulation, which was significantly abrogated by treatment with Compound C, an inhibitor of AMP-activated protein kinase (AMPK). Taken together, these results suggested that MV exerted a pronounced effect upon improving hepatic steatosis through regulating the disequilibrium of lipid metabolism in the liver via an AMPK-dependent pathway, providing a potential lead compound candidate for preventing nonalcoholic fatty liver disease.

In Vitro Anticancer Activity of Virgin Coconut Oil and its Fractions in Liver and Oral Cancer Cells

2020 ◽  
Vol 19 (18) ◽  
pp. 2223-2230 ◽  
Author(s):  
Poonam Verma ◽  
Sanjukta Naik ◽  
Pranati Nanda ◽  
Silvi Banerjee ◽  
Satyanarayan Naik ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Oral Cancer ◽  
Anticancer Activity ◽  
Cancer Cells ◽  
Cell Line ◽  
Coconut Oil ◽  
Virgin Coconut Oil ◽  
Anticancer Efficacy ◽  
Oral Cancer Cells

Background: Coconut oil is an edible oil obtained from fresh, mature coconut kernels. Few studies have reported the anticancer role of coconut oil. The fatty acid component of coconut oil directly targets the liver by portal circulation and as chylomicron via lymph. However, the anti-cancer activity of coconut oil against liver cancer cells and oral cancer cells is yet to be tested. The active component of coconut oil, that is responsible for the anticancer activity is not well understood. In this study, three different coconut oils, Virgin Coconut Oil (VCO), Processed Coconut Oil (PCO) and Fractionated Coconut Oil (FCO), were used. Objective: Based on previous studies, it can be hypothesized that fatty acids in coconut oil may have anticancer potential and may trigger cell death in cancer cell lines. Methods: Each cell line was treated with different concentrations of Virgin Coconut Oil (VCO), Processed Coconut Oil (PCO) and Fractionated Coconut Oil (FCO). The treated cells were assayed by MTT after 72 hr of incubation. The fatty acid composition of different coconut oils was analyzed by gas chromatography. Result: Different concentrations of coconut oils were used to treat the cells. Interestingly, the anticancer efficacy of VCO, PCO and FCO was not uniform, rather the efficacy varied from cell line to cell line. Only 20% VCO showed significant anticancer activity in HepG2 cells in comparison to 80% PCO against the KB cell line. Remarkably, 20% of PCO and 5% of FCO showed potential growth inhibition in the KB cell line as compared to 80% PCO in HepG2 cells. Moreover, there was a difference in the efficacy of VCO, PCO and FCO, which might be due to their fatty acid composition. Comparing the anticancer efficacy of VCO, PCO and FCO in this study helped to predict which class of fatty acids and which fatty acid might be associated with the anticancer activity of VCO. Conclusion: This study shows that VCO, PCO and FCO have anticancer efficacy and may be used for the treatment of cancer, especially liver and oral cancer.

Placental Accumulation of Triacylglycerols in Gestational Diabetes Mellitus and Its Association with Altered Fetal Growth are Related to the Differential Expressions of Proteins of Lipid Metabolism

2020 ◽  
Author(s):  
Manoharan Balachandiran ◽  
Zachariah Bobby ◽  
Gowri Dorairajan ◽  
Sajini Elizabeth Jacob ◽  
Victorraj Gladwin ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Fatty Acid ◽  
Lipid Metabolism ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Fetal Growth ◽  
Fatty Acid Synthase ◽  
Regulatory Element ◽  
Acid Oxidation ◽  
Placental Proteins

Abstract Introduction Gestational diabetes mellitus (GDM) exhibit altered placental lipid metabolism. The molecular basis of this altered metabolism is not clear. Altered placental expression of proteins of lipogenesis and fatty acid oxidation may be involved in the placental accumulation of triacylglycerols (TG). The present study was aimed at investigating the differential expressions of placental proteins related to lipid metabolism among GDM women in comparison with control pregnant women (CPW) and to correlate them with maternal and fetal lipid parameters as well as altered fetal growth. Materials and Methods Maternal blood, cord blood, and placental samples were collected from GDM and CPW. The biochemical parameters, glucose, lipid profile and free fatty acids (FFA) were measured. The placental TG content was measured. Differential placental expressions of proteins; phosphatidylinositol-3-kinase (PI3K) p85α, PI3K p110α,liver X receptor alpha (LXRα), sterol regulatory element binding protein1(SREBP1), fatty acid synthase (FAS), stearyl CoA desaturase1 (SCD1), lipoprotein lipase (LPL),Peroxisome proliferator-activated receptor (PPAR)α and PPARγ were analysed by western blotting and immunohistochemistry. Results Placental protein expressions of PI3K p110α, LXRα, FAS, SCD1, and LPL were found to be significantly higher, whereas PPARα and PPARγ were lower in GDM women compared with CPW. The placental TG content and cord plasma FFA were increased in GDM women compared with CPW. The placental TG content positively correlated with Ponderal index of GDM new-borns. Conclusion Differential expressions of placental proteins related to lipid metabolism in GDM might have led to placental TG accumulation. This might have contributed to the fetal overgrowth in GDM.

I. Molecular mechanism for polyunsaturated fatty acid regulation of gene transcription

2001 ◽  
Vol 281 (4) ◽  
pp. G865-G869 ◽  
Author(s):  
Steven D. Clarke
Keyword(s):  
Gene Expression ◽  
Fatty Acids ◽  
Fatty Acid ◽  
Dna Binding ◽  
Regulatory Element ◽  
Health Benefit ◽  
Acid Oxidation ◽  
Nuclear Factor ◽  
Genes Encoding ◽  
Nuclear Abundance

This review addresses the hypothesis that polyunsaturated fatty acids (PUFA), particularly those of the n-3 family, play pivotal roles as “fuel partitioners” in that they direct fatty acids away from triglyceride storage and toward oxidation and they enhance glucose flux to glycogen. In doing this, PUFA may reduce the risk of enhanced cellular apoptosis associated with excessive cellular lipid accumulation. PUFA exert their beneficial effects by upregulating the expression of genes encoding proteins involved in fatty acid oxidation while simultaneously downregulating genes encoding proteins of lipid synthesis. PUFA govern oxidative gene expression by activating the transcription factor peroxisome proliferator-activated receptor-α. PUFA suppress lipogenic gene expression by reducing the nuclear abundance and DNA binding affinity of transcription factors responsible for imparting insulin and carbohydrate control to lipogenic and glycolytic genes. In particular, PUFA suppress the nuclear abundance and expression of sterol regulatory element binding protein-1 and reduce the DNA binding activities of nuclear factor Y, stimulatory protein 1, and possibly hepatic nuclear factor-4. Collectively, the studies discussed suggest that the fuel “repartitioning” and gene expression actions of PUFA should be considered among the criteria used in defining the dietary needs of n-6 and n-3 fatty acids and in establishing the dietary ratio of n-6 to n-3 fatty acids needed for optimum health benefit.

scholarly journals Epstein–Barr virus-encoded latent membrane protein 1 and B-cell growth transformation induces lipogenesis through fatty acid synthase.

2020 ◽  
Author(s):  
Michael Hulse ◽  
Sarah M Johnson ◽  
Sarah Boyle ◽  
Lisa Beatrice Caruso ◽  
Italo Tempera
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
B Cells ◽  
Cell Growth ◽  
B Cell ◽  
Fatty Acid Synthase ◽  
De Novo ◽  
Ectopic Expression ◽  
Barr Virus ◽  
Growth Transformation

Latent membrane protein 1 (LMP1) is the major transforming protein of Epstein-Barr virus (EBV) and is critical for EBV-induced B-cell transformation in vitro. Several B-cell malignancies are associated with latent LMP1-positive EBV infection, including Hodgkin’s and diffuse large B-cell lymphomas. We have previously reported that promotion of B cell proliferation by LMP1 coincided with an induction of aerobic glycolysis. To further examine LMP1-induced metabolic reprogramming in B cells, we ectopically expressed LMP1 in an EBV-negative Burkitt’s lymphoma (BL) cell line preceding a targeted metabolic analysis. This analysis revealed that the most significant LMP1-induced metabolic changes were to fatty acids. Significant changes to fatty acid levels were also found in primary B cells following EBV-mediated B-cell growth transformation. Ectopic expression of LMP1 and EBV-mediated B-cell growth transformation induced fatty acid synthase (FASN) and increased lipid droplet formation. FASN is a crucial lipogenic enzyme responsible for de novo biogenesis of fatty acids in transformed cells. Furthermore, inhibition of lipogenesis caused preferential killing of LMP1-expressing B cells and significantly hindered EBV immortalization of primary B-cells. Finally, our investigation also found that USP2a, a ubiquitin-specific protease, is significantly increased in LMP1-positive BL cells and mediates FASN stability. Our findings demonstrate that ectopic expression of LMP1 and EBV-mediated B-cell growth transformation leads to induction of FASN, fatty acids and lipid droplet formation, possibly pointing to a reliance on lipogenesis. Therefore, the use of lipogenesis inhibitors could potentially be used in the treatment of LMP1+ EBV associated malignancies by targeting a LMP1-specific dependency on lipogenesis. Importance Despite many attempts to develop novel therapies, EBV-specific therapies currently remain largely investigational and EBV-associated malignancies are often associated with a worse prognosis. Therefore, there is a clear demand for EBV-specific therapies for both prevention and treatment of viral-associated malignancies. Non-cancerous cells preferentially obtain fatty acids from dietary sources whereas cancer cells will often produce fatty acids themselves by de novo lipogenesis, often becoming dependent on the pathway for cell survival and proliferation. LMP1 and EBV-mediated B-cell growth transformation leads to induction of FASN, a key enzyme responsible for the catalysis of endogenous fatty acids. Preferential killing of LMP1-expressing B cells following inhibition of FASN suggests that targeting LMP-induced lipogenesis could be an effective strategy in treating LMP1-positive EBV-associated malignancies. Importantly, targeting unique metabolic perturbations induced by EBV could be a way to explicitly target EBV-positive malignancies and distinguish their treatment from EBV-negative counterparts.

scholarly journals Effect of Breed on Transcriptional and Protein Expression of Lipogenic Enzymes in Tail and Subcutaneous Adipose Tissue from Two Grazing Breeds of Lambs

Animals ◽  
2019 ◽  
Vol 9 (2) ◽  
pp. 64
Author(s):  
María Gallardo ◽  
Luis Arias-Darraz ◽  
Juan Cárcamo
Keyword(s):  
Fatty Acid ◽  
Protein Expression ◽  
Mrna Expression ◽  
Fatty Acid Synthase ◽  
Regulatory Element ◽  
Subcutaneous Fat ◽  
Human Consumption ◽  
Meat Industry ◽  
Lipogenic Enzymes ◽  
Expression Levels

This experiment was carried out to determine the effect of breed on mRNA and protein expression levels of lipogenic enzymes acetyl-CoA carboxylase α (ACC), fatty acid synthase (FAS), stearoyl-CoA desaturase 1 (SCD1) plus sterol regulatory element binding transcription factor 1c (SREBP1c) in the subcutaneous fat (SCF) from the back of the animal, and tail fat (TF) of both Chilota and Suffolk Down lambs grazing Calafatal. Eight Chilota and six Suffolk Down 2-month-old male lambs were allocated to graze a “Calafatal”, a typical secondary succession of Chiloé Archipelago, Chile. After 62 d, lambs were slaughtered according to Chile’s meat industry standards. Fatty acid profile, RT-qPCR, and Western blot analyses from SCF and TF samples were performed. Although the mRNA expression levels of ACC, FAS, SCD1 and SREBP1c in SCF did not differ significantly between breeds (p > 0.05), a trend to higher mRNA expression of FAS and SREBP1c in TF from Chilota lambs was observed (p = 0.06). On the other hand, FAS levels in SCF were higher in Chilota than in Suffolk Down lambs (p < 0.02), although Suffolk Down showed higher fat contents and saturated fatty acid (SFA) proportions than Chilota lambs (p < 0.01). The FAS protein expression in TF was similar in both breeds (p > 0.05). Although the fat content was higher in Suffolk Down than in Chilota lambs (p < 0.01), the SFA proportions were similar in both breeds. Finally, it can be concluded that although mRNA expression of enzymes was similar in both breeds, there were differences in some protein levels in the SCF, partially related with the fatty acid profiles, thus affecting the selection of lamb breed either for human consumption or experimental purposes.

scholarly journals Cholesterol biosynthesis supports the growth of hepatocarcinoma lesions depleted of fatty acid synthase in mice and humans

Gut ◽  
2019 ◽  
Vol 69 (1) ◽  
pp. 177-186 ◽  
Author(s):  
Li Che ◽  
Wenna Chi ◽  
Yu Qiao ◽  
Jie Zhang ◽  
Xinhua Song ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Cell Lines ◽  
Knockout Mice ◽  
Fatty Acid Synthase ◽  
De Novo ◽  
Therapeutic Option ◽  
Regulatory Element ◽  
Cholesterol Biosynthesis ◽  
Dominant Negative ◽  
Comparative Genomic

ObjectiveIncreased de novo fatty acid (FA) synthesis and cholesterol biosynthesis have been independently described in many tumour types, including hepatocellular carcinoma (HCC).DesignWe investigated the functional contribution of fatty acid synthase (Fasn)-mediated de novo FA synthesis in a murine HCC model induced by loss of Pten and overexpression of c-Met (sgPten/c-Met) using liver-specificFasnknockout mice. Expression arrays and lipidomic analysis were performed to characterise the global gene expression and lipid profiles, respectively, of sgPten/c-Met HCC from wild-type andFasnknockout mice. Human HCC cell lines were used for in vitro studies.ResultsAblation ofFasnsignificantly delayed sgPten/c-Met-driven hepatocarcinogenesis in mice. However, eventually, HCC emerged inFasnknockout mice. Comparative genomic and lipidomic analyses revealed the upregulation of genes involved in cholesterol biosynthesis, as well as decreased triglyceride levels and increased cholesterol esters, in HCC from these mice. Mechanistically, loss ofFasnpromoted nuclear localisation and activation of sterol regulatory element binding protein 2 (Srebp2), which triggered cholesterogenesis. Blocking cholesterol synthesis via the dominant negative form of Srebp2 (dnSrebp2) completely prevented sgPten/c-Met-driven hepatocarcinogenesis inFasnknockout mice. Similarly, silencing ofFASNresulted in increasedSREBP2activation and hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase (HMGCR)expression in human HCC cell lines. Concomitant inhibition of FASN-mediated FA synthesis and HMGCR-driven cholesterol production was highly detrimental for HCC cell growth in culture.ConclusionOur study uncovers a novel functional crosstalk between aberrant lipogenesis and cholesterol biosynthesis pathways in hepatocarcinogenesis, whose concomitant inhibition might represent a therapeutic option for HCC.

scholarly journals Sterol regulatory element binding protein and dietary lipid regulation of fatty acid synthesis in the mammary epithelium

2010 ◽  
Vol 299 (6) ◽  
pp. E918-E927 ◽  
Author(s):  
Michael C. Rudolph ◽  
Jenifer Monks ◽  
Valerie Burns ◽  
Meridee Phistry ◽  
Russell Marians ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Mammary Gland ◽  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
De Novo ◽  
Regulatory Element ◽  
Acid Synthesis ◽  
De Novo Lipogenesis ◽  
Mrna Levels ◽  
Sterol Regulatory Element

The lactating mammary gland synthesizes large amounts of triglyceride from fatty acids derived from the blood and from de novo lipogenesis. The latter is significantly increased at parturition and decreased when additional dietary fatty acids become available. To begin to understand the molecular regulation of de novo lipogenesis, we tested the hypothesis that the transcription factor sterol regulatory element binding factor (SREBF)-1c is a primary regulator of this system. Expression of Srebf1c mRNA and six of its known target genes increased ≥2.5-fold at parturition. However, Srebf1c-null mice showed only minor deficiencies in lipid synthesis during lactation, possibly due to compensation by Srebf1a expression. To abrogate the function of both isoforms of Srebf1, we bred mice to obtain a mammary epithelial cell-specific deletion of SREBF cleavage-activating protein (SCAP), the SREBF escort protein. These dams showed a significant lactation deficiency, and expression of mRNA for fatty acid synthase ( Fasn), insulin-induced gene 1 ( Insig1), mitochondrial citrate transporter ( Slc25a1), and stearoyl-CoA desaturase 2 ( Scd2) was reduced threefold or more; however, the mRNA levels of acetyl-CoA carboxylase-1α ( Acaca) and ATP citrate lyase ( Acly) were unchanged. Furthermore, a 46% fat diet significantly decreased de novo fatty acid synthesis and reduced the protein levels of ACACA, ACLY, and FASN significantly, with no change in their mRNA levels. These data lead us to conclude that two modes of regulation exist to control fatty acid synthesis in the mammary gland of the lactating mouse: the well-known SREBF1 system and a novel mechanism that acts at the posttranscriptional level in the presence of SCAP deletion and high-fat feeding to alter enzyme protein.

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