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α 1-acid glycoprotein inhibits lipogenesis in neonatal swine adipose tissue1

Published online by Cambridge University Press:  26 November 2015

T. G. Ramsay*
Affiliation:
Animal Biosciences and Biotechnology Laboratory, Beltsville Agricultural Research Center, Animal and Natural Resources Institute, United States Department of Agriculture, Agricultural Research Service, Beltsville, MD 20705, USA
L. Blomberg
Affiliation:
Animal Biosciences and Biotechnology Laboratory, Beltsville Agricultural Research Center, Animal and Natural Resources Institute, United States Department of Agriculture, Agricultural Research Service, Beltsville, MD 20705, USA
T. J. Caperna
Affiliation:
Animal Biosciences and Biotechnology Laboratory, Beltsville Agricultural Research Center, Animal and Natural Resources Institute, United States Department of Agriculture, Agricultural Research Service, Beltsville, MD 20705, USA
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Abstract

Serum α1-acid glycoprotein (AGP) is elevated during late gestation and at birth in the pig and rapidly declines postnatally. In contrast, the pig is born with minimal lipid stores in the adipose tissue, but rapidly accumulates lipid during the first week. The present study examined if AGP can affect adipose tissue metabolism in the neonatal pig. Isolated cell cultures or tissue explants were prepared from dorsal subcutaneous adipose tissue of preweaning piglets. Porcine AGP was used at concentrations of 0, 100, 1000 and 5000 ng/ml medium in 24 h incubations. AGP reduced the messenger RNA (mRNA) abundance of the lipogenic enzymes, malic enzyme (ME), fatty acid synthase and acetyl coA carboxylase by at least 40% (P<0.001). The activity of ME and citrate lyase were also reduced by AGP (P<0.05). Glucose oxidation was reduced by treatment with 5000 ng AGP/ml medium (P<0.05). The 14C-glucose incorporation into fatty acids was reduced by ~25% by AGP treatment for 24 h with 1000 ng AGP/ml medium (P<0.05). The decrease in glucose metabolism by AGP appears to function through an inhibition in insulin-mediated glucose oxidation and incorporation into fatty acids. This was supported by the analysis of the mRNA abundance for sterol regulatory element-binding protein (SREBP), carbohydrate regulatory element-binding protein (ChREBP) and insulin receptor substrate 1 (IRS1), which all demonstrated reductions of at least 23% in response to AGP treatment (P<0.05). These data demonstrate an overall suppression of lipogenesis due to AGP inhibition of lipogenic gene expression in vitro, which the metabolic data and SREBP, ChREBP and IRS1 gene expression analysis suggest is through an inhibition in insulin-mediated events. Second, these data suggest that AGP may contribute to limiting lipogenesis within adipose tissue during the perinatal period, as AGP levels are highest for any serum protein at birth.

Type
Research Article
Copyright
© The Animal Consortium 2015. This is a work of the U.S. Government and is not subject to copyright protection in the United States. 

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Footnotes

1

Mention of trade name, proprietary product or vendor does not constitute a guarantee or warranty of the product by the US Department of Agriculture or imply its approval to the exclusion of other products or vendors that also may be suitable.

References

Azain, MJ and Martin, RJ 1983. Effect of genetic obesity on the regulation of hepatic fatty acid metabolism. American Journal of Physiology 244, R400R406.Google ScholarPubMed
Boncela, J, Papiewska, I, Fijalkowska, I, Walkowiak, B and Cierniewski, CS 2001. Acute phase protein alpha 1-acid glycoprotein interacts with plasminogen activator inhibitor type 1 and stabilizes its inhibitory activity. Journal of Biological Chemistry 276, 3530535311.Google Scholar
Cagen, LM, Deng, X, Wilcox, HG, Park, EA, Raghow, R and Elam, MB 2005. Insulin activates the rat sterol-regulatory-element-binding protein 1c (SREBP-1c) promoter through the combinatorial actions of SREBP, LXR, Sp-1 and NF-Y cis-acting elements. The Biochemical Journal 385, 207216.Google Scholar
Caperna, TJ, Shannon, AE, Blomberg, LA, Stoll, M and Ramsay, TG 2013. Identification of alpha-1 acid glycoprotein (AGP) as a potential marker of impaired growth in the newborn piglet. Reproduction, Fertility, and Development 25, 11261133.CrossRefGoogle ScholarPubMed
Chen, HH, Lin, JH, Fung, HP, Ho, LL, Yang, PC, Lee, WC, Lee, YP and Chu, RM 2003. Serum acute phase proteins and swine health status. Canadian Journal of Veterinary Research 27, 283290.Google Scholar
Conde, J, Scotece, M, Gómez, R, López, V, Gómez-Reino, JJ, Lago, F and Gualillo, O 2011. Adipokines: biofactors from white adipose tissue. A complex hub among inflammation, metabolism, and immunity. Biofactors 37, 413420.Google Scholar
Cottam, GL and Srere, PA 1969. The sulfhydryl groups of citrate cleavage enzyme. Archives of Biochemistry and Biophysics 130, 304311.Google Scholar
DeCingolani, CE 1972. Glucose metabolism by isolated fat cells from diabetic rats. Archives internationales de physiologie et de biochimie 80, 269274.Google Scholar
Dif, N, Euthine, V, Gonnet, E, Laville, M, Vidal, H and Lefai, E 2006. Insulin activates human sterol-regulatory-element-binding protein-1c (SREBP-1c) promoter through SRE motifs. The Biochemical Journal 400, 179188.Google Scholar
Foufelle, F and Ferré, P 2002. New perspectives in the regulation of hepatic glycolytic and lipogenic genes by insulin and glucose: a role for the transcription factor sterol regulatory element binding protein-1c. The Biochemical Journal 366, 377391.CrossRefGoogle ScholarPubMed
Garssen, GJ, Spencer, GS, Colenbrander, B, Macdonald, AA and Hill, DJ 1983. Lack of effect of chronic hyperinsulinaemia on growth and body composition in the fetal pig. Biology of the Neonate 44, 234242.Google Scholar
Gondret, F, Perruchot, MH, Tacher, S, Bérard, J and Bee, G 2011. Differential gene expressions in subcutaneous adipose tissue pointed to a delayed adipocytic differentiation in small pig fetuses compared to their heavier siblings. Differentiation 81, 253260.Google Scholar
Hausman, GJ 1992. Responsiveness to adipogenic agents in stromal-vascular cultures derived from lean and preobese pig fetuses: an ontogeny study. Journal of Animal Science 70, 106114.Google Scholar
Hauner, H, Entenmann, G, Wabitsch, M, Gaillard, D, Ailhaud, G, Negrel, R and Pfeiffer, EF 1989. Promoting effect of glucocorticoids on the differentiation of human adipocyte precursors cells cultures in a chemically defined medium. Journal of Clinical Investigation 84, 16631670.Google Scholar
He, Z, Jiang, T, Wang, Z, Levi, M and Li, J 2004. Modulation of carbohydrate response element-binding protein gene expression in 3T3-L1 adipocytes and rat adipose tissue. American Journal of Physiology Endocrinology and Metabolism 287, E424430.Google Scholar
Heegaard, PM, Miller, I, Sorensen, NS, Soerensen, KE and Skovgaard, K 2013. Pig α1-acid glycoprotein: characterization and first description in any species as a negative acute phase protein. PLoS One 8, e68110. doi: 10.1371/journal.pone.0068110.Google Scholar
Hochepied, T, Berger, FG, Baumann, H and Libert, C 2003. α1-Acid glycoprotein: an acute phase protein with inflammatory and immunomodulating properties. Cytokine and Growth Factor Reviews 14, 2534.Google Scholar
Itoh, H, Tamura, K, Izumi, M, Motoi, Y, Kidoguchi, K and Funayama, Y 1992. The influence of age and health status on the serum alpha1-acid glycoprotein level of conventional and specific pathogen-free pigs. Canadian Journal of Veterinary Research 57, 7478.Google Scholar
Iritani, N, Fukuda, H and Tada, K 1996. Nutritional regulation of lipogenic enzyme gene expression in rat epididymal adipose tissue. Journal of Biochemistry 120, 242248.Google Scholar
Jiao, Q, Lei, M, Wang, L, Mo, X, Lan, J and Xiong, Y 2011. Developmental expression changes of the genes involved in IGFI signaling pathway in longissimus dorsi muscle of Tongcheng and Yorkshire pigs during postnatal growth. Molecular Biology Reports 38, 51335138.Google Scholar
Katiyar, SS, Cleland, WW and Porter, JW 1975. Fatty acid synthetase. A steady state kinetic analysis of the reaction catalyzed by the enzyme from pigeon liver. Journal of Biological Chemistry 250, 27092717.CrossRefGoogle ScholarPubMed
Lampreave, F and Piñeiro, A 1984. The major serum protein of fetal and newborn pigs: biochemical properties and identification as a fetal form of alpha 1-acid glycoprotein. International Journal of Biochemistry 16, 4753.Google Scholar
Lampreave, F and Piñeiro, A 1992. Concentrations of major plasma proteins in serum and whole-tissue extracts of porcine fetuses during development. Journal of Reproduction & Fertility 95, 441449.Google Scholar
Latasa, MJ, Griffin, MJ, Moon, YS, Kang, C and Sul, HS 2003. Occupancy and function of the -150 sterol regulatory element and -65 E-box in nutritional regulation of the fatty acid synthase gene in living animals. Molecular and Cellular Biology 23, 58965907.Google Scholar
Lee, YS, Choi, JW, Hwang, I, Lee, JW, Lee, JH, Kim, AY, Huh, JY, Koh, YJ, Koh, GY, Son, HJ, Masuzaki, H, Hotta, K, Alfadda, AA and Kim, JB 2010. Adipocytokine orosomucoid integrates inflammatory and metabolic signals to preserve energy homeostasis by resolving immoderate inflammation. Journal of Biological Chemistry 285, 2217422185.Google Scholar
Livak, KJ and Schmittgen, TD 2001. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods 25, 402408.Google Scholar
Martin, M, Tesouro, MA, González-Ramón, N, Piñeiro, A and Lampreave, F 2005. Major plasma proteins in pig serum during postnatal development. Reproduction, Fertility, and Development 17, 439445.Google Scholar
Mersmann, HJ 1974. Metabolic patterns in the neonatal swine. Journal of Animal Science 38, 10221030.Google Scholar
Mersmann, HJ, Goodman, JR and Brown, LJ 1975. Development of swine adipose tissue: morphology and chemical composition. Journal of Lipid Research 16, 269279.Google Scholar
Morise, A, Sève, B, Macé, K, Magliola, C, Le Huërou-luron, I and Louveau, I 2009. Impact of intrauterine growth retardation and early protein intake on growth, adipose tissue, and the insulin-like growth factor system in piglets. Pediatric Research 65, 4550.Google Scholar
Murata, H, Shimada, N and Yoshioka, M 2004. Current research on acute phase proteins in veterinary diagnosis: an overview. Veterinary Journal 168, 2840.Google Scholar
Nerurkar, LS, Marino, PA and Adams, DO 1981. Quantification of selected intracellular and secreted hydrolases of macrophages. In Manual of macrophage methodology (ed. HB Herscowitz, HT Holden, JA Bellanti and A Ghaffer), pp. 229247. Marcel Dekker, Inc., New York, NY, USA.Google Scholar
Ochoa, S 1955. “Malic” enzyme. Methods in Enzymology 1, 739753.Google Scholar
Postic, C, Dentin, R, Denechaud, PD and Girard, D 2007. ChREBP, a transcriptional regulator of glucose and lipid metabolism. Annual Review of Nutrition 27, 179192.Google Scholar
Oh, SY, Park, SK, Kim, JW, Ahn, YH, Park, SW and Kim, KS 2003. Acetyl-CoA carboxylase beta gene is regulated by sterol regulatory element-binding protein-1 in liver. Journal of Biological Chemistry 278, 2841028417.Google Scholar
Ramsay, TG and Richards, MP 2004. Hormonal regulation of leptin and leptin receptor expression in porcine subcutaneous adipose tissue. Journal of Animal Science 82, 34863492.Google Scholar
Ramsay, TG and Azain, MJ 2007. Comparison of gene expression in lean contemporary and crossbred obese swine. Adipocytes 2, 133142.Google Scholar
Ramsay, TG and Caperna, TJ 2009. Ontogeny of adipokine expression in neonatal pig adipose tissue. Comparative Biochemistry and Physiology B 152, 7278.Google Scholar
Ramsay, TG, Blomberg, L and Caperna, TJ 2013. Methyl-β-cyclodextrin alters adipokine gene expression and glucose metabolism in swine adipose tissue. Animal 7, 16901696.Google Scholar
Ramsay, TG, White, ME and Wolverton, CK 1989. Glucocorticoids and the differentiation of porcine preadipocytes. Journal of Animal Science 67, 22222229.Google Scholar
Rehfeldt, C and Kuhn, G 2006. Consequences of birth weight for postnatal growth performance and carcass quality in pigs as related to myogenesis. Journal of Animal Science 84 (suppl.), E113E123.Google Scholar
Rødgaard, T, Stagsted, J, Christoffersen, , Cirera, S, Moesgaard, SG, Sturek, M, Alloosh, M and Heegaard, PM 2013. Orosomucoid expression profiles in liver, adipose tissues and serum of lean and obese domestic pigs, Göttingen minipigs and Ossabaw minipigs. Veterinary Immunology and Immunopathology 151, 325330.Google Scholar
Stone, RT and Maurer, RA 1987. Cloning and developmental regulation of α1 acid glycoprotein in swine. Developmental Genetics 8, 295304.Google Scholar
Williams, JP, Weiser, MR, Pechet, TTV, Kobzik, L, Moore, FD and Hechtman, HB 1997. Acid glycoprotein reduces local and remote injuries after intestinal ischemia in the rat. American Journal of Physiology 273, G1031G1035.Google Scholar
Winer, J, Jung, CK, Shackel, I and Williams, PM 1999. Development and validation of real-time quantitative reverse transcriptase-polymerase chain reaction for monitoring gene expression in cardiac myocytes in vitro. Analytical Biochemistry 270, 4149.Google Scholar
Wolverton, CK, Azain, MJ, Duffy, JY, White, ME and Ramsay, TG 1992. Influence of somatotropin on lipid metabolism and IGF gene expression in porcine adipose tissue. American Journal of Physiology 263, E637E645.Google Scholar
Zhang, GH, Lu, JX, Chen, Y, Zhao, YQ, Guo, PH, Yang, JT and Zang, RX 2014. Comparison of the adipogenesis in intramuscular and subcutaneous adipocytes from Bamei and Landrace pigs. Biochemistry and Cell Biology 92, 259267.Google Scholar