A metabolic system-wide characterisation of the pig: a model for human physiology

Merrifield, Claire A; Lewis, Marie; Claus, Sandrine P.; Beckonert, Olaf; Dumas, Marc; Duncker, Swantje; Kochhar, Sunil; Rezzi, Serge; Lindon, John C.; Bailey, Mick; Holmes, Elaine; Nicholson, Jeremy K.

doi:10.1039/c1mb05023k

Cited by 104 publications

(106 citation statements)

References 47 publications

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“…Here, we use pig as model based on the higher similarities of pig to human in physiology and genome (Merrifield et al, 2011). Cumulative evidence strongly indicates that reduction in mitochondrial function and oxidative metabolism in skeletal muscle during critical period of fetus growth and development was associated with the greater incidence of T2D and insulin resistance in later life (Shelley et al, 2009;Latouche et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial biogenesis is decreased in skeletal muscle of pig fetuses exposed to maternal high-energy diets

Zou

et al. 2017

Animal

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Mitochondria plays an important role in the regulation of energy homeostasis. Moreover, mitochondrial biogenesis accompanies skeletal myogenesis, and we previously reported that maternal high-energy diet repressed skeletal myogenesis in pig fetuses. Therefore, the aim of this study was to evaluate the effects of moderately increased maternal energy intake on skeletal muscle mitochondrial biogenesis and function of the pig fetuses. Primiparous purebred Large White sows were allocated to a normal energy intake group (NE) as recommended by the National Research Council (NRC) and a high energy intake group (HE, 110% of NRC recommendations). On day 90 of gestation, fetal umbilical vein blood and longissimus (LM) muscle were collected. Results showed that the weight gain of sows fed HE diet was higher than NE sows on day 90 of gestation ( P < 0.05). Maternal HE diet increased fetal umbilical vein serum triglyceride and insulin concentrations ( P < 0.05), and tended to increase the homeostasis model assessment index ( P = 0.08). Furthermore, HE fetuses exhibited increased malondialdehyde concentration ( P < 0.05), and decreased activities of antioxidative enzymes ( P < 0.05) and intracellular NAD + level ( P < 0.05) in LM muscle. These alterations in metabolic traits of HE fetuses were accompanied by reduced mitochondrial DNA amount ( P < 0.05) and down-regulated messenger RNA expression levels of genes responsible for mitochondrial biogenesis and function ( P < 0.05). Our results suggest that moderately increased energy supply during gestation decreases mitochondrial biogenesis, function and antioxidative capacity in skeletal muscle of pig fetuses.

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Section: Discussionmentioning

confidence: 99%

Mitochondrial biogenesis is decreased in skeletal muscle of pig fetuses exposed to maternal high-energy diets

Zou

et al. 2017

Animal

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“…variations can be compared (Merrifield et al, 2011;Benahmed et al, 2014). Several studies analysed metabolites in different pig biological systems (tissues or biofluids) to try to capture metabolomic signatures that could explain, at least in part, differences between the tested experimental designs, including different diets, other treatments or environmental factors (e.g.…”

Section: Discussionmentioning

confidence: 99%

Metabolomics evidences plasma and serum biomarkers differentiating two heavy pig breeds

Bovo

Mazzoni

Galimberti

et al. 2016

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In pigs, many production traits are known to vary among breeds or lines. These traits can be considered end phenotypes or external traits as they are the final results of complex biological interactions and processes whose fine biological mechanisms are still largely unknown. This study was designed to compare plasma and serum metabolomic profiles between animals of two heavy pig breeds (12 Italian Large White and 12 Italian Duroc), testing indirectly the hypothesis that different genetic backgrounds might be the determining factors of differences observed on the level of metabolites in the analyzed biofluids between breeds. We used a targeted metabolomic approach based on mass spectrometric detection of about 180 metabolites and applied a statistical validation pipeline to identify differences in the metabolomic profiles of the two heavy pig breeds. Blood samples were collected after jugulation at the slaughterhouse and prepared for metabolomics analysis that was carried out using the Biocrates AbsoluteIDQ p180 Kit, covering five different biochemical classes: glycerophospholipids, amino acids, biogenic amines, hexoses and acylcarnitines. A statistical pipeline that included the selection of the most relevant metabolites differentiating the two breeds by sparse Partial Least Squares Discriminant Analysis (sPLS-DA) was coupled with a stability test and significance test determined with leave one out and permutation procedures. sPLS-DA plots clearly separated the pigs of the two investigated breeds. A few metabolites (a total of five metabolites considering the two biofluids) involved in key metabolic pathways largely contributed to these differences between breeds. In particular, a higher level of the sphingomyelins SM (OH) C14:1 (both in plasma and serum), SM (OH) C16:1 (in serum) and SM C16:0 (in serum) were observed in Italian Duroc than in Italian Large White pigs and the inverse was for the biogenic amine kynurenine (in plasma). The level of another biogenic amine (acetylornithine) was higher in Italian Large White than in Italian Duroc pigs in both analysed biofluids. These results provided biomarkers that could be important to understand the biological differences between these two heavy pig breeds. In particular, according to the functional role played by sphingomyelins in obesity-induced inflammatory responses, it could be possible to speculate that a higher level of sphingomyelins in Italian Duroc might be related to the higher interrmuscular fat deposition of this breed compared with the Italian Large White. Additional studies will be needed to evaluate the relevance of these biomarkers for practical applications in pig breeding and nutrition.Keywords: pig breeding, metabolites, molecular phenotypes, metabolic pathway, production traits ImplicationsThis study showed that different pig breeds are characterized by different metabolomics profiles. The statistical approach that was adopted identified a few biomarkers whose level in plasma and serum described the differences between two heavy pig breeds. T...

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“…metagenomic (i.e., gut microbiota) effects and environmental factors. Indeed, both system-wide (i.e., whole organism) and organ-specific changes in biochemical processes have components driven by these factors (Martin et al 2009a, b;Nicholson et al 2005;Claus et al 2011;Mestdagh et al 2011;Merrifield et al 2011;Wikoff et al 2009).…”

Section: Electronic Supplementary Materialsmentioning

confidence: 99%

Current status on genome–metabolome-wide associations: an opportunity in nutrition research

et al. 2012

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Genome-wide association studies (GWASs) have become a very important tool to address the genetic origin of phenotypic variability, in particular associated with diseases. Nevertheless, these types of studies provide limited information about disease etiology and the molecular mechanisms involved. Recently, the incorporation of metabolomics into the analysis has offered novel opportunities for a better understanding of disease-related metabolic deregulation. The pattern emerging from this work is that gene-driven changes in metabolism are prevalent and that common genetic variations can have a profound impact on the homeostatic concentrations of specific metabolites. A particularly interesting aspect of this work takes into account interactions of environment and lifestyle with the genome and how this interaction translates into changes in the metabolome. For instance, the role of PY-ROXD2 in trimethylamine metabolism points to an interaction between host and microbiome genomes (host/ microbiota). Often, these findings reveal metabolic deregulations, which could eventually be tuned with a nutritional intervention. Here we review the development of gene-metabolism association studies from a single-gene/ single-metabolite to a genome-wide/metabolome-wide approach and highlight the conceptual changes associated with this ongoing transition. Moreover, we report some of our recent GWAS results on a cohort of 265 individuals from an ethnically diverse population that validate and refine previous findings on gene-urine metabolism interactions. Specifically, our results confirm the effect of PYROXD2 polymorphisms on trimethylamine metabolism and suggest that a previously reported association of N-acetylated compounds with the ALMS1/NAT8 locus is driven by SNPs in the ALMS1 gene.

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A metabolic system-wide characterisation of the pig: a model for human physiology

Cited by 104 publications

References 47 publications

Mitochondrial biogenesis is decreased in skeletal muscle of pig fetuses exposed to maternal high-energy diets

Mitochondrial biogenesis is decreased in skeletal muscle of pig fetuses exposed to maternal high-energy diets

Metabolomics evidences plasma and serum biomarkers differentiating two heavy pig breeds

Current status on genome–metabolome-wide associations: an opportunity in nutrition research

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