Integration of liver gene co-expression networks and eGWAs analyses highlighted candidate regulators implicated in lipid metabolism in pigs

Ballester, María; Ramayo-Caldas, Yuliaxis; Revilla, Manuel; Corominas, Jordi; Castelló, Anna; Estellé, Jordi; Fernández, Ana; Folch, Josep María

doi:10.1038/srep46539

Cited by 31 publications

(43 citation statements)

References 76 publications

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“…In addition, in an eGWAS performed in liver of BC1_LD individuals, a cis‐variant (SNP MARC0115316 ) located more than 700 kb upstream of FABP5 was associated with FABP5 mRNA levels (Ballester et al . ), supporting the different regulatory control of FABP s among tissues. Apart from the cis FABP4 :g.2634_2635insC polymorphism, we identified four trans‐acting regions on chromosomes SSC7, SSC9, SSC11 and SSC14 associated with FABP4 mRNA expression in backfat.…”

Section: Discussionmentioning

confidence: 70%

Association of genetic variants and expression levels of porcine FABP4 and FABP5 genes

et al. 2017

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The FABP4 and FABP5 genes, coding for fatty acid transport proteins, have long been studied as positional candidate genes for SSC4 QTL affecting fat deposition and composition traits in pigs. Polymorphisms in these genes, FABP4:g.2634_2635insC and FABP5:g.3000T>G, have previously been associated with fatness traits in an Iberian by Landrace cross (IBMAP). The aim of the present work was to evaluate the functional implication of these genetic variants. For this purpose, FABP4 and FABP5 mRNA expression levels in 114 BC1_LD animals (25% Iberian × 75% Landrace) were analyzed using real-time quantitative PCR in backfat and muscle. FABP4 gene expression in backfat, but not in muscle, was associated with FABP4:g.2634_2635insC. In contrast, FABP5:g.3000T>G was not associated with gene expression levels. An expression-based genome-wide association study highlighted the FABP4:g.2634_2635insC polymorphism as the polymorphism most associated with FABP4 gene expression in backfat. Furthermore, other genomic regions associated in trans with the mRNA expression of FABP4 in backfat and FABP5 in muscle were also identified. Finally, two putative transcription binding sites for PPARG and NR4A2 may be affected by the FABP4:g.2634_2635insC polymorphism, modifying FABP4 gene expression. Our results reinforce FABP4 as a candidate gene for fatness traits on SSC4.

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Section: Discussionmentioning

confidence: 70%

Association of genetic variants and expression levels of porcine FABP4 and FABP5 genes

et al. 2017

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“…All target-primers, except for the IL10 gene 76 , were designed using PrimerExpress 2.0 software (Applied Biosystems) and are shown in Supplementary Table S15. The ACTB and HPRT1 genes were used as endogenous controls 77 . All assays were tested and PCR efficiencies were evaluated by performing standard curves with a four-fold dilutions series (1/4, 1/16, 1/64, 1/256, 1/1024) per triplicate of a pool of 5 cDNA samples in an Applied Biosystems 7500 Real-Time PCR System (Applied Biosystems, Inc.; Foster City, CA).…”

Section: Validation Of Differentially Expressed Genes By Rt-qpcr a Qmentioning

confidence: 99%

Dietary intake of bioactive ingredients impacts liver and adipose tissue transcriptomes in a porcine model of prepubertal early obesity

Ballester

Quintanilla

Ortega

et al. 2020

Sci Rep

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Global prevalence of obesity has increased to epidemic proportions over the past 40 years, with childhood obesity reaching alarming rates. In this study, we determined changes in liver and adipose tissue transcriptomes of a porcine model for prepubertal early obesity induced by a high-calorie diet and supplemented with bioactive ingredients. A total of 43 nine-weeks-old animals distributed in four pens were fed with four different dietary treatments for 10 weeks: a conventional diet; a western-type diet; and a western-type diet with Bifidobacterium breve and rice hydrolysate, either adding or not omega-3 fatty acids. Animals fed a western-type diet increased body weight and total fat content and exhibited elevated serum concentrations of cholesterol, whereas animals supplemented with bioactive ingredients showed lower body weight gain and tended to accumulate less fat. An RNA-seq experiment was performed with a total of 20 animals (five per group). Differential expression analyses revealed an increase in lipogenesis, cholesterogenesis and inflammatory processes in animals on the western-type diet while the supplementation with bioactive ingredients induced fatty acid oxidation and cholesterol catabolism, and decreased adipogenesis and inflammation. These results reveal molecular mechanisms underlying the beneficial effects of bioactive ingredient supplementation in an obese pig model. administration of Bifidobacterium breve B-3 modified the hepatic expression of genes related to lipid metabolism and response to stress 4 . A reduction in body fat has been also observed in healthy pre-obese individuals receiving Bifidobacterium breve B-3, but no significant improvement of blood parameters was found 5 . In partial agreement, studies with rodent models of obesity have demonstrated the anti-obesity effect of n-3 polyunsaturated fatty acids (PUFA). Reduction of fat mass was predominantly observed in mice fed a HFD and supplemented with n-3 PUFA (reviewed in 6 ). However, the effects of n-3 PUFA in human obesity remain inconclusive. On the other hand, rice proteins and their hydrolysates added to high fat and/or high cholesterol diets have shown to have anti-obesity and hypocholesterolemic effects through the effective modulation of cholesterol and triglyceride metabolism, and the activity of hepatic genes related to lipid metabolism 7,8 .Overall, these experimental evidences reinforce the relevance of using bioactive dietetic supplements to prevent and treat obesity. However, as most of these studies were performed in rodent models, the underlying biological mechanisms determining anti-obesity effects are difficult to translate into humans, due to the vast differences between these species at the physiological and metabolic level 9 . In contrast, pigs are excellent models for human obesity and its comorbidities, given their similarity in terms of anatomy, physiology, metabolism, and genetics 9-11 .To date, a limited number of pig models for childhood obesity have been developed by short term (≤ 12 wk.) dietary interven...

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“…Primers spanning exon-exon boundaries, or alternatively binding at different exons (in order to avoid the amplification of residual contaminating genomic DNA) were designed with the Primer3 software ( Untergasser et al, 2012 ). Primers employed in the amplification of the β-actin ( ACTB ), TATA-Box Binding Protein ( TBP ), and hypoxanthine phosphoribosyltransferase 1 ( HPRT1 ) were reported by Ballester et al (2017) . Primer sequences are available in Supplementary File 1 .…”

Section: Methodsmentioning

confidence: 99%

Analysing the Expression of Eight Clock Genes in Five Tissues From Fasting and Fed Sows

et al. 2018

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In a previous study, we observed that circadian clock genes are differentially expressed in the skeletal muscle of fasting and fed sows. The goal of the current work was to investigate if these genes are also differentially expressed in tissues containing the central (hypothalamus) and peripheral (duodenum, dorsal fat, muscle, and liver) clocks. As animal material, we used 12 sows that fasted 12 h before slaughtering (T0) and 12 sows that were fed ad libitum 7 h prior slaughtering (T2). Tissue samples were collected immediately after slaughter and total RNA was subsequently extracted. The expression of the ARNTL, BHLHE40, CRY2, NPAS2, NR1D1, PER1, PER2, and SIK1 genes was measured by quantitative reverse transcription PCR. The numbers of clock genes showing differential expression before and after feeding varied depending on the tissue i.e., four in dorsal fat and duodenum, six in skeletal muscle, and seven in the liver. In contrast, none of the eight analysed genes displayed a significant differential expression in hypothalamus, the tissue where the central clock resides. This result supports that the differential expression of clock genes in the four tissues mentioned above is probably induced by nutrition and not by the central clock entrained by light. Moreover, we have observed that the NPAS2 and ARNTL genes display positive log2(FC) values in the five tissues under analysis, whilst the CRY2, PER1 (except dorsal fat) and PER2 (except hypothalamus) genes generally show negative log2(FC) values. Such result might be explained by the existence of a negative feedback loop between the ARNTL/NPAS2 and CRY/PER genes. Collectively, these results support that nutrition plays an important role in modulating the timing of porcine peripheral circadian clocks. Such regulation could be essential for coordinating the subsequent metabolic response to nutrient supply.

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Integration of liver gene co-expression networks and eGWAs analyses highlighted candidate regulators implicated in lipid metabolism in pigs

Cited by 31 publications

References 76 publications

Association of genetic variants and expression levels of porcine FABP4 and FABP5 genes

Association of genetic variants and expression levels of porcine FABP4 and FABP5 genes

Dietary intake of bioactive ingredients impacts liver and adipose tissue transcriptomes in a porcine model of prepubertal early obesity

Analysing the Expression of Eight Clock Genes in Five Tissues From Fasting and Fed Sows

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