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Title: Tumor necrosis a regulation of adipokine gene expression in neonatal adipose tissue

Author
item Ramsay, Timothy
item Stoll, Margo
item Caperna, Thomas
item CONDE-AGUILERA, J - Universidad De Granada

Submitted to: Veterinary Research Communications
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/4/2012
Publication Date: 3/1/2013
Citation: Ramsay, T.G., Stoll, M.J., Caperna, T.J., Conde-Aguilera, J.A. 2013. Tumor necrosis a regulation of adipokine gene expression in neonatal adipose tissue. Veterinary Research Communications. 37(1):1-10.

Interpretive Summary: Parturition and the early neonatal period of development is a time period of dramatic changes for the neonate. The animal is challenged by both environmental and physiological stressors. As the animal is rapidly developing during the neonatal period, it is susceptible to a variety of factors that can alter its, all of which can lead to repartitioning of nutrients away from adipose tissue and lipid accretion. As the adipose tissue is the primary site of energy storage in the preweaning piglet, stressors that can alter this accretion could have severe consequences on the metabolic viability of the neonate. One of the greatest challenges in swine production is the risk of infection in the farrowing house. Infection produces significant changes in cytokine balance. Tumor necrosis a is of particular interest as it responds to infectious challenge, metabolically can promote lipolysis and negative energy balance and it is produced and secreted by the adipose tissue itself. The present study was designed to determine if TNFa can alter cytokine (adipokines) gene expression within the adipose tissue of neonatal swine. Cell cultures were prepared from neonatal pig adipose tissue using standard procedures and permitted to accumulate lipid. Following 9 days of lipid filling, these adipose cultures were used for experiments. Cultures were incubated with 0, 2.5, 5.0 or 10 ng of porcine TNFa for 2, 4 or 24 hours. Samples were then extracted for RNA using spin columns and total RNA was reverse transcribed and used in real-time PCR analysis to assess the expression of adipokines. Leptin and macrophage migration inhibitory factor 1 gene expression were acutely reduced by TNFa (P < 0.05) whereas adiponectin gene expression was depressed only at 24 hours (P < 0.05). Interleukin 15, monocyte chemotactic protein 1 and interleukin 6 mRNA abundance were increased at all 3 timepoints examined (P < 0.05), but with differences in time of maximal response. These data indicate that TNFa is a potent regulator of adipokine expression. Adipokines mediate many of the metabolic processes within the adipose tissue. Neonatal survival in the piglet is dependent upon the ability to rapidly accumulate lipids within the adipose tissue in the first weeks of life and also to be able to rapidly mobilize them when necessary. Understanding the regulation of these adipokines and their interplay in modifying neonatal adipose tissue metabolism may provide essential information to reduce neonatal mortality in piglets.

Technical Abstract: The neonatal period is also a time of significant stress and susceptibility to infection, conditions which favor the secretion of tumor necrosis a. The present study was designed to determine if TNFa can alter adipokine gene expression within the adipose tissue of neonatal swine. Primary stromal vascular cell cultures were prepared from neonatal pig adipose tissue using standard procedures, permitted to proliferate, differentiate and accumulate lipid. Following lipid filling, cultures were washed, incubated overnight without hormones and then were incubated with 0, 2.5, 5.0 or 10 ng TNFa for 2, 4 or 24 hours in DMEM/F12 containing 0.5% BSA (n =4 experiments). RNA was extracted and used for real-time PCR analysis to assess the expression of a variety of adipokines. Leptin and MIF mRNA abundance were acutely reduced by TNFa (P = 0.022 and P = 0.030, respectively) whereas adiponectin gene expression was depressed only at 24 hours (P =0.017). Interleukin 15, MCP and interleukin 6 mRNA abundance were increased at all 3 timepoints examined (P = 0.040; P < 0.001; P = 0.029; respectively). Understanding the regulation of these adipokines and their interplay in modifying neonatal adipose tissue metabolism may provide necessary information to reduce neonatal mortality in piglets.