The main adipogenic transcription factor PPAR possesses high affinity to 2,4-TZD, a member of the Thiazolidinedione family of insulin-sensitizing compounds used as adipogenic agents. We evaluated 2,4-TZD’s effect on bovine growth and PPAR tissue expression. Seventeen Limousin bulls (18 month-old; 350？kg body weight (BW)) were assigned into 2 treatments: control and 2,4-TZD (8？mg/70？kg BW) and were fed until bulls reached 500？kg BW. They were weighed and their blood was sampled. DNA, RNA, and protein were determined in liver; skeletal muscle; subcutaneous (SC), omental, perirenal adipose tissues (AT) to determine protein synthesis rate and cellular size. Expression of PPAR mRNA was measured in liver and muscle (PPAR , - , and - ) and SC adipose tissue ( ) by real-time PCR. No significant differences were found ( ) in weight gain, days on feed, and carcass quality. Muscle synthesis was greater in controls ( ); cell size was larger with 2,4-TZD ( ). PPAR , - , and - expressions with 2,4-TZD in liver were lower ( ) than in muscle. No differences were found for PPARγ mRNA expression in SCAT. The results suggest the potential use of 2,4-TZD in beef cattle diets, because it improves AT differentiation, liver, and muscle fatty acid oxidation that, therefore, might improve energy efficiency. 1. Introduction Peroxisome proliferator-activated receptors (PPAR) are ligand-activated transcription factors that belong to the nuclear hormone receptor superfamily. Three isotypes have been identified in lower vertebrates and mammals: PPARα or NR1C1; PPARβ/δ or NR1C2, also called NUC-1 or FAAR; PPARγ or NR1C3. These receptors exhibit different tissue distribution and functions and, to some extent, different ligand specificities. Mechanistically, they form heterodimers with the retinoid X receptor (RXR) and activate transcription by binding to a specific DNA element, termed the peroxisome proliferator response element (PPRE), in the regulatory region of a variety of genes encoding proteins that are involved in lipid metabolism [1] and energy balance [2–4]. The Thiazolidinediones (TZDs) are PPARγ agonists that possess clinical antidiabetic efficacy, mainly through their actions in adipose tissues [3]. The influence of TZD on adipose differentiation has been demonstrated through modifications on adipose tissue deposition and increases of intramuscular (IM) fat in meat animals [5, 6]; on the other hand, Michalik et al. [3] mentioned that some TZD may act on different PPAR, especially PPARα. Marbling or IM fat has been positively correlated with meat quality [7] because of the
References
[1]
J. G. Kang, C. Y. Park, S. H. Ihm et al., “Mechanisms of adipose tissue redistribution with rosiglitazone treatment in various adipose depots,” Metabolism, vol. 59, no. 1, pp. 46–53, 2010.
[2]
A. Aranda and A. Pascual, “Nuclear hormone receptors and gene expression,” Physiological Reviews, vol. 81, no. 3, pp. 1269–1304, 2001.
[3]
L. Michalik, J. Auwerx, J. P. Berger et al., “International union of pharmacology. LXI. Peroxisome proliferator-activated receptors,” Pharmacological Reviews, vol. 58, no. 4, pp. 726–741, 2006.
[4]
A. Yessoufou and W. Wahli, “Multifaceted roles of peroxisome proliferator-activated receptors (PPARs) at the cellular and whole organism levels,” Swiss Medical Weekly, vol. 140, no. 3071, pp. 4–10, 2010.
[5]
S. I. Torii, T. Kawada, K. Matsuda, T. Matsui, T. Ishihara, and H. Yano, “Thiazolidinedione induces the adipose differentiation of fibroblast-like cells resident within bovine skeletal muscle,” Cell Biology International, vol. 22, no. 6, pp. 421–427, 1998.
[6]
G. J. Hausman, S. P. Poulos, T. D. Pringle, and M. J. Azain, “The influence of thiazolidinediones on adipogenesis in vitro and in vivo: potential modifiers of intramuscular adipose tissue deposition in meat animals,” Journal of Animal Science, vol. 86, no. 14, pp. E236–243, 2008.
[7]
U.S.D.A. United States Meat Grading and Certification Branch, Agricultural Marketing Service. Washington, DC, USA, U.S.D.A. MGC Instruction, 2009.
[8]
K. M. Killinger, C. R. Calkins, W. J. Umberger, D. M. Feuz, and K. M. Eskridge, “Consumer visual preference and value for beef steaks differing in marbling level and color,” Journal of Animal Science, vol. 82, no. 11, pp. 3288–3293, 2004.
[9]
W. S. Pitchford, M. P. B. Deland, B. D. Siebert, A. E. O. Malau-Aduli, and C. D. K. Bottema, “Genetic variation in fatness and fatty acid composition of crossbred cattle,” Journal of Animal Science, vol. 80, no. 11, pp. 2825–2832, 2002.
[10]
T. L. Wheeler, L. V. Cundiff, S. D. Shackelford, and M. Koohmaraie, “Characterization of biological types of cattle (Cycle VII): carcass, yield, and longissimus palatability traits,” Journal of Animal Science, vol. 83, no. 1, pp. 196–207, 2005.
[11]
CICUAE, Comité Institucional para Cuidado y Uso de los Animales de Experimentación. Especificaciones técnicas para la producción, cuidado y uso de los animales de experimentación. Rumiantes. Facultad de Medicina Veterinaria y Zootecnia. Vol. 8. México, D.F., México: Universidad Nacional Autónoma de México, pp. 1–8, 2008.
[12]
Diabetes mellitus tipo II. AVANDIA. 16 ed. Multicolor. México, D.F., México: Vademécum Farmaceútico IPE, 2008.
[13]
O. Kuda, B. Stankova, E. Tvrzicka et al., “Prominent role of liver in elevated plasma palmitoleate levels in response to rosiglitazone in mice fed high-fat diet,” Journal of Physiology and Pharmacology, vol. 60, no. 4, pp. 135–140, 2009.
[14]
K. L. Smith, S. E. Stebulis, M. R. Waldron, and T. R. Overton, “Prepartum 2,4-thiazolidinedione alters metabolic dynamics and dry matter intake of dairy cows,” Journal of Dairy Science, vol. 90, no. 8, pp. 3660–3670, 2007.
[15]
Norma Oficial Mexicana, Proceso sanitario de la carne. Secretaria de Agricultura, Ganadería y Desarrollo Rural. SAGARPA. Estados Unidos Mexicanos. NOM-009-ZOO-1996. Diario Oficial de la Federación, pp. 1–13, 1996.
[16]
Norma Oficial Mexicana, Sacrificio humanitario de los animales domésticos y silvestres. Secretaria de Agricultura, Ganadería y Desarrollo Rural. SAGARPA. Estados Unidos Mexicanos. NOM-033-ZOO-1995. Diario Oficial de la Federación, pp. 1–19, 1996.
[17]
N.A.M.P. North American Meat Processors Association, The Meat Buyer’s Guide. Cortes para servicio de alimentación. Spanish beef notebook. Bovino beef. 6th ed. Washington, DC, USA, N.A.M.P. 2009.
[18]
R. A. Garcia and J. G. Phillips, “Physical distribution and characteristics of meat and bonemeal protein,” Journal of the Science of Food and Agriculture, vol. 89, no. 2, pp. 329–336, 2009.
[19]
M. M. Bradford, “A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein dye binding,” Analytical Biochemistry, vol. 72, no. 1-2, pp. 248–254, 1976.
[20]
C. R. Reynoso, O. Mora, V. Nieves, A. Shimada, and E. González De Mejía, “β-Carotene and lutein in forage and bovine adipose tissue in two tropical regions of Mexico,” Animal Feed Science and Technology, vol. 113, no. 1–4, pp. 183–190, 2004.
[21]
P. Sripalakit, P. Neamhom, and A. Saraphanchotiwitthaya, “High-performance liquid chromatographic method for the determination of pioglitazone in human plasma using ultraviolet detection and its application to a pharmacokinetic study,” Journal of Chromatography B, vol. 843, no. 2, pp. 164–169, 2006.
[22]
A. M. Muxlow, S. Fowles, and P. Russell, “Automated high-performance liquid chromatography method for the determination of rosiglitazone in human plasma,” Journal of Chromatography B, vol. 752, no. 1, pp. 77–84, 2001.
[23]
J. He, Y. F. Hu, L. F. Duan et al., “Sensitive and selective liquid chromatography-mass spectrometry method for the quantification of rosiglitazone in human plasma,” Journal of Pharmaceutical and Biomedical Analysis, vol. 43, no. 2, pp. 580–585, 2007.
[24]
SAS Institute and Inc, “SAS/STAT User’s guide,” release 9.0 ed. Cary, NC, USA, SAS Institute, Inc., 2006.
[25]
C. V. Rizos, M. S. Elisaf, D. P. Mikhailidis, and E. N. Liberopoulos, “How safe is the use of thiazolidinediones in clinical practice?” Expert Opinion on Drug Safety, vol. 8, no. 1, pp. 15–32, 2009.
[26]
J. Wilding, “Thiazolidinediones, insulin resistance and obesity: finding a balance,” International Journal of Clinical Practice, vol. 60, no. 10, pp. 1272–1280, 2006.
[27]
K. L. Smith, W. R. Butler, and T. R. Overton, “Effects of prepartum 2,4-thiazolidinedione on metabolism and performance in transition dairy cows,” Journal of Dairy Science, vol. 92, no. 8, pp. 3623–3633, 2009.
[28]
M. Dervillé, S. Patin, and L. Avon, “Les races allaitantes. Limousine,” in Races Bovines de France, France Agricole, France Upra Sélection, 2009.
[29]
S. Kushibiki, K. Hodate, H. Shingu et al., “Insulin resistance induced in dairy steers by tumor necrosis factor alpha is partially reversed by 2,4-thiazolidinedione,” Domestic Animal Endocrinology, vol. 21, no. 1, pp. 25–37, 2001.
[30]
P. Tontonoz and B. M. Spiegelman, “Fat and beyond: the diverse biology of PPARγ,” Annual Review of Biochemistry, vol. 77, pp. 289–312, 2008.
[31]
A. M. Sharma and B. Staels, “Peroxisome proliferator-activated receptor γ and adipose tissue—understanding obesity-related changes in regulation of lipid and glucose metabolism,” Journal of Clinical Endocrinology and Metabolism, vol. 92, no. 2, pp. 386–395, 2007.
[32]
T. B. Koenen, C. J. Tack, J. M. Kroese et al., “Pioglitazone treatment enlarges subcutaneous adipocytes in insulin-resistant patients,” Journal of Clinical Endocrinology and Metabolism, vol. 94, no. 11, pp. 4453–4457, 2009.
[33]
P. Eguinoa, S. Brocklehurst, A. Arana, J. A. Mendizabal, R. G. Vernon, and A. Purroy, “Lipogenic enzyme activities in different adipose depots of Pirenaican and Holstein bulls and heifers taking into account adipocyte size,” Journal of Animal Science, vol. 81, no. 2, pp. 432–440, 2003.
[34]
F. Haugen and C. A. Drevon, “The interplay between nutrients and the adipose tissue: plenary lecture,” Proceedings of the Nutrition Society, vol. 66, no. 2, pp. 171–182, 2007.
[35]
G. J. Hausman, M. V. Dodson, K. Ajuwon et al., “The biology and regulation of preadipocytes and adipocytes in meat animals,” Journal of Animal Science, vol. 87, no. 4, pp. 1218–1246, 2009.
[36]
A. J. Scheen, “Pharmacokinetic interactions with thiazolidinediones,” Clinical Pharmacokinetics, vol. 46, no. 1, pp. 1–12, 2007.
[37]
N. L. Julie, I. M. Julie, A. I. Kende, and G. L. Wilson, “Mitochondrial dysfunction and delayed hepatotoxicity: another lesson from troglitazone,” Diabetologia, vol. 51, no. 11, pp. 2108–2116, 2008.
[38]
M. Bedoucha, E. Atzpodien, and U. A. Boelsterli, “Diabetic KKAy mice exhibit increased hepatic PPARγ1 gene expression and develop hepatic steatosis upon chronic treatment with antidiabetic thiazolidinediones,” Journal of Hepatology, vol. 35, no. 1, pp. 17–23, 2001.
[39]
M. C. Sugden, M. G. Zariwala, and M. J. Holness, “PPARs and the orchestration of metabolic fuel selection,” Pharmacological Research, vol. 60, no. 3, pp. 141–150, 2009.
[40]
H. Yki-J？rvinen, “Thiazolidinediones and the liver in humans,” Current Opinion in Lipidology, vol. 20, no. 6, pp. 477–483, 2009.
[41]
M. Wierzbicki, A. Chabowski, M. Zendzian-Piotrowska, and J. Gorski, “Differential effects of in vivo PPAR α and γ activation on fatty acid transport proteins expression and lipid content in rat liver,” Journal of Physiology and Pharmacology, vol. 60, no. 1, pp. 99–106, 2009.
[42]
A. L. Hevener, W. He, Y. Barak et al., “Muscle-specific Pparg deletion causes insulin resistance,” Nature Medicine, vol. 9, no. 12, pp. 1491–1497, 2003.
[43]
A. H. V. Remels, R. C. J. Langen, P. Schrauwen, G. Schaart, A. M. W. J. Schols, and H. R. Gosker, “Regulation of mitochondrial biogenesis during myogenesis,” Molecular and Cellular Endocrinology, vol. 315, no. 1-2, pp. 113–120, 2010.
[44]
P. De Lange, A. Lombardi, E. Silvestri, F. Goglia, A. Lanni, and M. Moreno, “Peroxisome proliferator-activated receptor delta: a conserved director of lipid homeostasis through regulation of the oxidative capacity of muscle,” PPAR Research, vol. 2008, Article ID 172676, 7 pages, 2008.
[45]
M. Schuler, F. Ali, C. Chambon et al., “PGC1α expression is controlled in skeletal muscles by PPARβ, whose ablation results in fiber-type switching, obesity, and type 2 diabetes,” Cell Metabolism, vol. 4, no. 5, pp. 407–414, 2006.
[46]
D. Holst, S. Luquet, K. Kristiansen, and P. A. Grimaldi, “Roles of peroxisome proliferator-activated receptors delta and gamma in myoblast transdifferentiation,” Experimental Cell Research, vol. 288, no. 1, pp. 168–176, 2003.
[47]
K. M. Schoenberg, K. L. Perfield, J. K. Farney, B. J. Bradford, Y. R. Boisclair, and T. R. Overton, “Effects of prepartum 2,4-thiazolidinedione on insulin sensitivity, plasma concentrations of tumor necrosis factor alpha and leptin, and adipose tissue gene expression,” Journal of Dairy Science, vol. 94, no. 11, pp. 5523–5532, 2011.
[48]
K. M. Schoenberg and T. R. Overton, “Effects of plane of nutrition and 2,4-thiazolidinedione on insulin responses and adipose tissue gene expression in dairy cattle during late gestation,” Journal of Dairy Science, vol. 94, no. 12, pp. 6021–6035, 2011.
[49]
R. L. Baldwin, K. R. McLeod, J. P. McNamara, T. H. Elsasser, and R. G. Baumann, “Influence of abomasal carbohydrates on subcutaneous, omental, and mesenteric adipose lipogenic and lipolytic rates in growing beef steers,” Journal of Animal Science, vol. 85, no. 9, pp. 2271–2282, 2007.
[50]
B. Soret, H. J. Lee, E. Finley, S. C. Lee, and R. G. Vernon, “Regulation of differentiation of sheep subcutaneous and abdominal preadipocytes in culture,” Journal of Endocrinology, vol. 161, no. 3, pp. 517–524, 1999.
[51]
G. E. Walker, B. Verti, P. Marzullo et al., “Deep subcutaneous adipose tissue: a distinct abdominal adipose depot,” Obesity, vol. 15, no. 8, pp. 1933–1943, 2007.
[52]
G. S. Harper and D. W. Pethick, “The physiology of marbling: what is it, and why does it develop?” in Proceedings of the Marbling Symposium, N. Jones, Ed., pp. 36–45, Cooperative Research Centre for Cattle and Beef Quality, Armidale, Coffs Harbour, NSW, Australia, 2001.
[53]
B. J. Johnson and K. Y. Chung, “Alterations in the physiology of growth of cattle with growth-enhancing compounds,” Veterinary Clinics of North America, vol. 23, no. 2, pp. 321–332, 2007.
