Genes Related to Fat Metabolism in Pigs and Intramuscular Fat Content of Pork: A Focus on Nutrigenetics and Nutrigenomics

Fat metabolism and intramuscular fat (IMF) are qualitative traits in pigs whose development are influenced by several genes and metabolic pathways. Nutrigenetics and nutrigenomics offer prospects in estimating nutrients required by a pig. Application of these emerging fields in nutritional science provides an opportunity for matching nutrients based on the genetic make-up of the pig for trait improvements. Today, integration of high throughput “omics” technologies into nutritional genomic research has revealed many quantitative trait loci (QTLs) and single nucleotide polymorphisms (SNPs) for the mutation(s) of key genes directly or indirectly involved in fat metabolism and IMF deposition in pigs. Nutrient–gene interaction and the underlying molecular mechanisms involved in fatty acid synthesis and marbling in pigs is difficult to unravel. While existing knowledge on QTLs and SNPs of genes related to fat metabolism and IMF development is yet to be harmonized, the scientific explanations behind the nature of the existing correlation between the nutrients, the genes and the environment remain unclear, being inconclusive or lacking precision. This paper aimed to: (1) discuss nutrigenetics, nutrigenomics and epigenetic mechanisms controlling fat metabolism and IMF accretion in pigs; (2) highlight the potentials of these concepts in pig nutritional programming and research.

Conditional Loss of Ikkα in Sp7/osterix+ Cells Has No Effect on Bone, but Leads to Cell Autonomous, Age-related Loss of Peripheral Fat

NF-κB has been reported to both promote and inhibit bone formation. To further explore its role in osteolineage cells, we conditionally deleted IKKα, an upstream kinase required for non-canonical NF-κB activation, using Sp7/Osterix (Osx)-Cre. Surprisingly, we found no effect on either cancellous or cortical bone, even following mechanical loading. However, we noted that IKKα conditional knockout (cKO) mice began to lose body weight after 6 months of age with severe reductions in fat mass in geriatric animals. Low levels of recombination at the IKKα locus were detected in fat pads isolated from 15 month old cKO mice. To determine if these effects were mediated by unexpected deletion of IKKα in peripheral adipocytes, we looked for Osx-Cre-mediated recombination in fat using reporter mice, which showed increasing degrees of reporter activation in adipocytes with age up to 18 months. Since Osx-Cre-driven recombination in peripheral adipocytes increases over time, we conclude that loss of fat in aged cKO mice is most likely caused by progressive deficits of IKKα in adipocytes. To further explore the effect of IKKα loss on fat metabolism, we challenged mice with a high fat diet at 2 months of age, finding that cKO mice gained less weight and showed improved glucose metabolism, compared to littermate controls. Thus, Osx-Cre mediated recombination beyond bone, including within adipocytes, should be considered as a possible explanation for extraskeletal phenotypes, especially in aging and metabolic studies.

The New Role of AMP-Activated Protein Kinase in Regulating Fat Metabolism and Energy Expenditure in Adipose Tissue

Obesity is characterized by excessive accumulation of fat in the body, which is triggered by a body energy intake larger than body energy consumption. Due to complications such as cardiovascular diseases, type 2 diabetes (T2DM), obstructive pneumonia and arthritis, as well as high mortality, morbidity and economic cost, obesity has become a major health problem. The global prevalence of obesity, and its comorbidities is escalating at alarming rates, demanding the development of additional classes of therapeutics to reduce the burden of disease further. As a central energy sensor, the AMP-activated protein kinase (AMPK) has recently been elucidated to play a paramount role in fat synthesis and catabolism, especially in regulating the energy expenditure of brown/beige adipose tissue and the browning of white adipose tissue (WAT). This review discussed the role of AMPK in fat metabolism in adipose tissue, emphasizing its role in the energy expenditure of brown/beige adipose tissue and browning of WAT. A deeper understanding of the role of AMPK in regulating fat metabolism and energy expenditure can provide new insights into obesity research and treatment.

Nitrogen-Doped Multiwalled Carbon Nanotubes Inhibit Fat Deposition via Immunomodulatory Actions

Multiwalled carbon nanotubes (MWCNTs) offer immense opportunities to deliver drug and biomolecules to targeted tissues. However, it’s unclear for us about their effects on fat metabolism. Here, we demonstrate that nitrogen-doped carboxylate-functionalized MWCNTs (N-MWCNTs) inhibit fat deposition both in vivo and in vitro primarily by suppressing adipogenesis. N-MWCNTs show good biocompatability in HEK293 mammalian cells. Intramuscular administration of N-MWCNTs does not affect the body weight gain and feed intake of mice, but reduces the fat mass. In in vitro-cultured adipocytes, N-MWCNTs suppress fat accumulation, accompanying with decreased and increased expression of adipogenic and lipolysis genes, respectively. Transcriptome analysis further certified the N-MWCNT alteration of fat metabolism-related genes. Interestingly, we observed the phagocytosis of N-MWCNTs by macrophage-like cells via TEM imaging. The mRNA sequencing data also showed remarkable variation of the genes involved in TLRs pathway, ultimately leading to down- or up-regulation of inflammatory factors, of which Tnfα, Il1, Il7, Il10, and Il12 are decreased, whereas Il6 and Il11 are increased. In conclusion, N-MWCNTs induce the production of inflammatory cytokines through immune responses, which trigger the reduction of fat deposition. These findings support the usage of N-MWCNTs as a promising delivery for anti-obesity agents.

PSVI-24 Effects of early-life exposure to topsoil on the muscle fiber characteristics and gene expression of weaned piglets

The objective of this experiment was to investigate the influence of early exposure to topsoil on the muscle fiber characteristics and transcription-related myogenesis, intramuscular fat metabolism, muscle fiber types, and mTOR signaling pathway of weaned pigs. A Total of 180 piglets were separately assigned to the No soil, Antibacterial soil, and Normal soil group (each group, n = 60), and were fed ad libitum with common antibiotic-free corn-soybean meal diets until day-31. Ten pigs from each group with similar body weight were selected to be slaughtered, and the Longissimus dorsi (LD) muscle samples were collected for histological analysis and measurements of genes and protein expression levels. In the present study, the muscle fiber diameter and the area of the Normal soil and Antibacterial soil group were significantly higher than the No soil group (P < 0.05). The Normal soil significantly upregulated the gene expression of MyoG compared to No soil and Antibacterial soil groups (P < 0.05). The gene expression of CD36 and CPT-1 of the Normal soil group was significantly lower than the No soil group (P < 0.05), while HSL expression of the Normal soil group was significantly higher than the Antibacterial and No soil groups (P < 0.05). The MyHC I of the Normal soil group was significantly higher than the No soil group (P < 0.05), but the expression MyHC IIa was lower than the No soil group (P < 0.05). The protein expression expressed a similar result with gene expression. In addition, the Normal soil significantly increased the AMPK and mTOR phosphorylation compared to No soil and Antibacterial soil groups (P < 0.05). These data suggest that early exposure to topsoil regulates muscle fiber growth, modulates the expression pattern related to myogenesis, muscle fiber type, intramuscular fat metabolism, and increases the phosphorylation of mTOR and AMPK pathways.

251 Dietary Tryptophan Supplementation Improves Fat and Glucose Metabolism in Low Birthweight Piglets

Low birthweight (LBW) is associated with complications such as insulin resistance, obesity and metabolic disturbances of glucose and fat metabolism in early life. Dietary tryptophan (Trp) has been shown to reduce liver fat and suppress hyperglycemia in different species. The objective of this study was to assess the effect of dietary Trp on growth and glucose and fat metabolism in LBW pigs. Piglets (7-days old) weighing < 2 kg were considered as LBW while those weighting > 2 kg were considered as normal birthweight (NBW) and randomly allocated to 4 milk-replacer based treatments (n = 7–8): 1) NBW-0% Trp (NBW-T0), 2) LBW-0% Trp (LBW-T0), 3) LBW-0.4% Trp (LBW-T0.4), and 4) LBW-0.8% Trp (LBW-T0.8) for 3 weeks. Growth parameters and body weight were measured biweekly. At week 3, blood and tissue samples were collected in overnight-fasted pigs after a meal test. The mRNA and protein abundance of key glucose and lipid metabolism markers were determined using qPCR and western blot, respectively. Univariate GLM with Dunnett’s post-hoc test (SPSS®) was used to analyze the data. Growth parameters did not change among groups. Plasma triglycerides concentration was lower in LBW-T0.4 and LBW-T0.8 compared to LBW-T0. Blood glucose was lower in LBW-T0.8 than LBW-T0 at 60 min following the meal test. LBW-T0.8 had a lower transcript and protein abundance of liver glucose transporter-2 relative to LBW-T0. Compared to LBW-T0, LBW-T0.8 had a higher mRNA abundance of glucokinase and tended to have a lower transcript of phosphoenolpyruvate carboxykinase in liver. Relative to LBW-T0, LBW-T0.4 tended to have a lower protein abundance of sodium-glucose co-transporter 1 in jejunum. Compared to LBW-T0, LBW-T0.4 and LBW-T0.8 had a lower transcript of liver acetyl-CoA carboxylase and LBW-T0.4 had a higher transcript of liver 3-hydroxyacyl-CoA dehydrogenase. In conclusion, Trp supplementation reduced the lipogenesis and gluconeogenesis, but increased the glycolysis in LBW piglets.