Submitted to: Journal of Animal Science and Biotechnology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/21/2016
Publication Date: 4/14/2016
Citation: Ramsay, T.G., Stoll, M.J., Blomberg, L., Caperna, T.J. 2016. Regulation of cytokine gene expression by orosomucoid in neonatal swine adipose tissue. Journal of Animal Science and Biotechnology. 7:25.
Interpretive Summary: Recent studies from our laboratory have identified a specific protein as a potential marker for postnatal growth in the newborn pig. This protein is called alpha 1-acid glycoprotein (AGP) and has some roles in the immune system. We are attempting to identify its functions in the newborn piglet that might contribute to the pigs growth potential, as a faster growing pig makes more profit for the farmer. Recently, it was reported that AGP is present in the fat of adult pigs, especially obese pigs. Our research is the first to identify the expression of this protein in the fat of the newborn and to characterize the development of the expression of this protein within the body fat of the young, preweaning piglet. Further we identified the cells within the body fat that produce AGP. Using cell culture, piglet fat was incubated with increasing concentrations of pig AGP. Measurement of gene expression using molecular biology methods demonstrated that AGP reduced the expression of several proteins called cytokines that negatively impact growth and metabolism. This is the first time in any species that AGP has been shown to affect cytokine gene expression in adipose tissue or in the neonatal animal. This effect was specific as AGP did not affect cytokines that can positively impact growth and metabolism. These data are important as they help to explain a potential mechanism for why AGP at birth may be a marker for growth at later ages in the pig.
Technical Abstract: Adipose tissue has been reported to express a1-acid glycoprotein (AGP) mRNA, a protein with inflammatory and immunomodulatory properties. The present study was designed to determine if AGP can regulate pro-inflammatory or anti-inflammatory cytokine expression in neonatal porcine subcutaneous adipose tissue (SAT). Comparison of the postnatal development of AGP expression in liver with SAT demonstrated that liver AGP was highly expressed at d1 and decreased five-fold by d7 (P < 0.001), with no further change at d21, while SAT AGP gene expression was much lower than in liver (P < 0.001) and did not vary with age (P > 0.05). Isolation of adipocytes from stromal-vascular cells at d21 demonstrated no difference in AGP mRNA abundance between cell populations (P > 0.05). Primary cell cultures derived from neonatal SAT were used to examine AGP effects on cytokine gene expression. Cultures were differentiated in vitro and subsequently the adipocyte containing cultures were assessed for response to 24 hours of incubation with 0, 100, 1000 or 5000 ng porcine AGP/mL medium. Interleukin 6 gene expression was reduced by 32% (P < 0.01) as measured by real time PCR. The inhibition of macrophage migration inhibitory factor mRNA abundance by AGP was dose responsive (P < 0.01). AGP treatment also reduced the acute phase protein, plasminogen activator inhibitor 1 by 46% (P < 0.001). Interleukin 10, adiponectin and tumor necrosis a were unaffected by AGP treatment (P > 0.05). These data indicate that AGP has selective effects on cytokine expression by neonatal adipose tissue.