Metabolomic analysis of longissimus from underperforming piglets relative to piglets with normal preweaning growth

Authors: Ramsay, Timothy; Stoll, Margo; Shannon, Amy; Blomberg, Le Ann

Submitted to: Journal of Animal Science and Biotechnology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/21/2018
Publication Date: 4/28/2018
Citation: Ramsay, T.G., Stoll, M.J., Shannon, A.E., Blomberg, L. 2018. Metabolomic analysis of longissimus from underperforming piglets relative to piglets with normal preweaning growth. Journal of Animal and Biotechnology. https://doi.org/10.1186/s40104-018-0251-3.
DOI: https://doi.org/10.1186/s40104-018-0251-3

Interpretive Summary: Slow growing pigs result in a 90-million-dollar loss to the swine industry each year. The metabolic factors responsible for poor postnatal growth rate in some normal birth weight pigs is not understood. Scientists at the Agricultural Research Service, Beltsville, Maryland analyzed the composition of metabolites resulting from metabolic activity in skeletal muscle using metabolomic techniques. Metabolite analysis demonstrated reductions in carbohydrate metabolism, accompanied by increases in fat metabolism in the skeletal muscle of slow growing, preweaning pigs in comparison to pigs that grow at a normal rate. In addition, the skeletal muscle of the slow growing pig has an increased abundance of metabolites associated with protein breakdown, suggesting that these slower growing pigs are having a difficult time accumulating tissue protein. Perhaps most important, the skeletal muscle of the slow growing pig contains a small fraction of the energy necessary for protein and carbohydrate synthesis. These data provide the first evidence for mechanisms contributing to the slow growth in some normal birth weight piglets that result in increased intra-litter variability in weaning weights. Secondly, this study provides essential information and identifies potential targets for the development of nutritional intervention strategies to improve the growth, health and well-being of these slow growing piglets and thus improve the efficiency of swine production.

Technical Abstract: Background: The increase in intra-litter variability in weaning weight during the past twenty years has increased production costs in all in/all out swine production. One contributor to this variability is the normal birth weight pig that grows at a slower rate than littermates of similar birth weight. The metabolic consequences or causes of this perturbation in growth rate have not been identified. The aim of this study was to interrogate biochemical profiles manifested in skeletal muscle tissue originating from slow growing (SG) and faster growing littermates, with the aim of identifying metabolic pathways that are affected in skeletal muscle of the SG pig relative to its littermates (control). Samples of longissimus muscle from littermate pairs of pigs were collected at 21 days of age. Metabolomic analysis was performed by Metabolon, Inc. (Durham, NC). Results: Birth weights did not differ between littermate pairs of SG and Control pigs (P > 0.05). Weaning weights differed by 1.51 ± 0.19 kg (P < 0.001). Random forest (RF) analysis was effective at segregating muscle samples by growth rate, resulting in a predictive accuracy of 81% versus random segregation (50%). A decrease in many sugars in the pentose phosphate pathway (PPP) in the longissimus of the SG pig was detected (P < 0.05). Decreases were also apparent in glycolytic intermediates (glycerol 3-phosphate and lactate) and key glycolysis-derived intermediates (glucose-6-phosphate and fructose-6-phosphate) (P < 0.05). SG pigs had increased levels of several phospholipids, lysolipids, diacylglycerols, and sphingolipids (P < 0.05). Pathway analysis identified a cluster of molecules that are associated with muscle and collage/extracellular matrix breakdown that are affected in the SG pig (P < 0.05), with increases in glutamate and 3-methylhistidine and hydroxylated proline moieties. Nicotinate metabolism was altered in SG pigs, resulting in a 78% decrease in the nicotinamide adenine dinucleotide pool (P < 0.05). Conclusions: The impaired growth rate in the SG piglet relative to its littermate is associated with a shift from central carbon metabolism to lipid oxidation and an increase in muscle and extracellular matrix protein breakdown in longissimus, consistent with a more catabolic state in the SG pig. This parallels shifts in phospholipid and sphingolipid abundance that suggest changes in mitochondrial membrane composition and perhaps fluidity, accompanied by a reduction in NAD levels in the longissimus of SG pigs. These data provide the first evidence for biochemical mechanisms that contribute to the slow growth in some normal birth weight piglets that contribute to increased intra-litter variability in weaning weights and provides essential information and potential targets for the development of nutritional intervention strategies.