Rosiglitazone maleate increases weight gain and body fat content in growing lambs
F. T. Fahri A B C , I. J. Clarke D , D. W. Pethick A B , R. D. Warner A C and F. R. Dunshea A C E
+ Author Affiliations
- Author Affiliations
A Australian Sheep Industry CRC, University of New England, Armidale, NSW 2350, Australia.
B School of Veterinary and Life Sciences, Murdoch University, Murdoch, WA 6150, Australia.
C Faculty of Veterinary and Agricultural Sciences, The University of Melbourne, Parkville, Vic. 3010, Australia.
D Department of Physiology, Monash University, Clayton, Vic. 3800, Australia.
E Corresponding author. Email: fdunshea@unimelb.edu.au
Animal Production Science 56(7) 1185-1193 https://doi.org/10.1071/AN14885
Submitted: 17 October 2014 Accepted: 14 January 2015 Published: 22 April 2015
Abstract
Thiazolidinediones (TZD) are synthetic orally active peroxisome proliferator-activated receptor γ ligands used in the treatment of diabetes mellitus. The peroxisome proliferator-activated receptor γ gene plays an important role in regulating fat cell development, energy balance, and lipid metabolism in adipose and skeletal muscle tissue. There is interest in pharmacologic or nutritional means that may complement genetic techniques to improve growth and carcass composition of lambs and the major aim of the present study was to determine whether TZD impact on growth performance and meat quality of growing lambs. An initial study with four cross-bred lambs confirmed that rosiglitazone maleate is absorbed after oral dosing for 7 days. A second study was conducted with 30 cross-bred lambs to investigate the effects of sex (ewe vs wether) and dose of orally administered rosiglitazone maleate (0, 8 and 24 mg/day) for 55 days on growth performance, body composition, plasma metabolites and insulin and meat quality. Feed intake tended to increase linearly with dose of TZD (1521, 1816 and 1878 g/day for 0, 8 and 24 mg/day, P = 0.07) over the entire study, and particularly during the second half of the study (P < 0.05). There were both linear (P = 0.05) and quadratic (P = 0.04) responses in average daily gain to TZD (215, 270 and 261 g/day) with the quadratic response being most pronounced over the second half of the study (P = 0.004). As a result of the increased feed intake back fat (9.4, 11.1 and 13.5 mm, P < 0.001) and carcass fat (27.5%, 29.2% and 30.1%, P = 0.05) increased linearly with dose of TZD. However, there was no effect of TZD on internal fat depots. Plasma non-esterified acid concentrations increased linearly (0.37, 0.39 and 0.41 mM, P = 0.01) whereas plasma insulin concentrations (23.2, 26.9 and 20.9 mU/L, P = 0.05) and the homeostatic model assessment (6.82, 7.73 and 5.98, P = 0.05) exhibited quadratic responses to TZD. There were no significant effects of TZD on muscle pH, temperature or colour although muscle pH was higher at any temperature in ewes (+ 0.05 of a pH unit, P = 0.036) than in wethers. In conclusion, these data confirm that rosiglitazone maleate was rapidly absorbed from the digestive tract of growing ruminant lambs and was metabolically active. Oral TZD treatment appeared to mitigate against the inhibitory effect of carcass fatness on feed intake but the additional energy consumed was in turn deposited as fat.
Additional keywords: adipose tissue, body composition, feed intake, growth, lamb.
References
Anukulkitch C, Rao A, Dunshea FR, Clarke IJ (2009) A test of the lipostat theory in a seasonal (ovine) model under natural conditions reveals a close relationship between adiposity and melanin concentrating hormone expression. Domestic Animal Endocrinology 36, 138–151.| A test of the lipostat theory in a seasonal (ovine) model under natural conditions reveals a close relationship between adiposity and melanin concentrating hormone expression.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXjtFOjtrc%3D&md5=fd97867f8b93c997c743e5726365010fCAS | 19179037PubMed |
Arslanian S, Pyle L, Payan M, Bacha F, Caprio S, Haymond MW, Levitsky LL, Goland R, White NH, Willi SM (2013) Effects of metformin, metformin plus rosiglitazone, and metformin plus lifestyle on insulin sensitivity and beta-cell function in TODAY. Diabetes Care 36, 1749–1757.
Cottrell JJ, Warner RD, McDonagh MB, Dunshea FR (2004) Inhibition of endogenous nitric oxide production influences ovine hindlimb metabolism independently of insulin concentrations. Journal of Animal Science 82, 2558–2567.
Derosa G, Maffioli P (2012) Peroxisome proliferator-activated receptor-γ (PPAR-γ) agonists on glycemic control, lipid profile and cardiovascular risk. Current Molecular Pharmacology 5, 272–281.
| Peroxisome proliferator-activated receptor-γ (PPAR-γ) agonists on glycemic control, lipid profile and cardiovascular risk.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XhtVeqsLzF&md5=1b73cbbf0fc49d266f27171cc1565269CAS | 22122457PubMed |
Dunshea FR, Bell AW, Trigg TE (1990) Non-esterified fatty acid and glycerol kinetics and fatty acid re-esterification in goats during early lactation. The British Journal of Nutrition 64, 133–145.
| Non-esterified fatty acid and glycerol kinetics and fatty acid re-esterification in goats during early lactation.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK3cXkvFGgtL4%3D&md5=3e0b23646d46fa5b842f42e34d99c53aCAS | 2400758PubMed |
Dunshea FR, D’Souza DN, Pethick DW, Harper GS, Warner RD (2005) Effects of dietary factors and other metabolic modifiers on quality and nutritional value of meat. Meat Science 71, 8–38.
| Effects of dietary factors and other metabolic modifiers on quality and nutritional value of meat.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXmt1Wiu7g%3D&md5=5f78ff73e817487735d981dcc3d56837CAS | 22064049PubMed |
Dunshea FR, Suster D, Eason PJ, Warner RD, Hopkins DL, Ponnampalam EN (2007) Accuracy of dual energy X-ray absorptiometry, weight, longissimus lumborum muscle depth and GR fat depth to predict half carcass composition in sheep. Australian Journal of Experimental Agriculture 47, 1165–1171.
| Accuracy of dual energy X-ray absorptiometry, weight, longissimus lumborum muscle depth and GR fat depth to predict half carcass composition in sheep.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXhtVOisb3K&md5=e28f81c43f72bfcce0b856c03f4b085dCAS |
Fürnsinn C, Waldhäusl W (2002) Thiazolidinediones: metabolic actions in vitro. Diabetologia 45, 1211–1223.
| Thiazolidinediones: metabolic actions in vitro.Crossref | GoogleScholarGoogle Scholar | 12242453PubMed |
Gardner GE, Hopkins DL, Greenwood PL, Cake MA, Boyce MD, Pethick DW (2007) Sheep genotype, age and muscle type affect the expression of metabolic enzyme markers. Australian Journal of Experimental Agriculture 47, 1180–1189.
| Sheep genotype, age and muscle type affect the expression of metabolic enzyme markers.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXhtVOisb3L&md5=fbf0733779135fbe272ac69d39040180CAS |
Gervois P, Torra IP, Fruchart JC, Staels B (2000) Regulation of lipid and lipoprotein metabolism by PPAR activators. Clinical Chemistry and Laboratory Medicine 38, 3–11.
| Regulation of lipid and lipoprotein metabolism by PPAR activators.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3cXjt1Cntbs%3D&md5=190f822a3836e3843603422c8d17d1c6CAS | 10774955PubMed |
Hammarstedt A, Andersson CX, Rotter Sopasakis V, Smith U (2005a) The effect of PPARgamma ligands on the adipose tissue in insulin resistance. Prostaglandins, Leukotrienes, and Essential Fatty Acids 73, 65–75.
| The effect of PPARgamma ligands on the adipose tissue in insulin resistance.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXlt1SrtL4%3D&md5=8c7710723dd0ac718f83e4c81ff064edCAS | 15936183PubMed |
Hammarstedt A, Sopasakis VR, Gogg S, Jansson PA, Smith U (2005b) Improved insulin sensitivity and adipose tissue dysregulation after short-term treatment with pioglitazone in non-diabetic, insulin-resistant subjects. Diabetologia 48, 96–104.
| Improved insulin sensitivity and adipose tissue dysregulation after short-term treatment with pioglitazone in non-diabetic, insulin-resistant subjects.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXltVantQ%3D%3D&md5=5c322a935c6e1ce50c17a8eb465a7f06CAS | 15624096PubMed |
He J, Hu YF, Duun LF, Tan ZR, Wang LS, Wang D, Zhang W, Li Z, Liu J, Tu JH, Yao YM, Zhou H-H (2007) Sensitive and selective liquid chromatography–mass spectrometry method for the quantification of rosiglitazone in human plasma. Journal of Pharmaceutical and Biomedical Analysis 43, 580–585.
| Sensitive and selective liquid chromatography–mass spectrometry method for the quantification of rosiglitazone in human plasma.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXhsFarsQ%3D%3D&md5=fe0a1fb541026ca019dc46e87f8a159eCAS | 16934427PubMed |
Hegarty RS, Warner RD, Pethick DW (2006) Genetic and nutritional regulation of lamb growth and muscle characteristics. Australian Journal of Agricultural Research 57, 721–730.
| Genetic and nutritional regulation of lamb growth and muscle characteristics.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XlvFaqt7Y%3D&md5=51be031fda8a258ea3b1955de34359f0CAS |
Henry BA, Tilbrook AJ, Dunshea FR, Rao A, Blache D, Martin GB, Clarke IJ (2000) Long-term alterations in adiposity affect the expression of melanin-concentrating hormone and enkephalin but not proopiomelanocortin in the hypothalamus of ovariectomized ewes. Endocrinology 141, 1506–1514.
Houseknecht KL, Cole BM, Steele PJ (2002) Peroxisome proliferator-activated receptor gamma (PPARgamma) and its ligands: a review. Domestic Animal Endocrinology 22, 1–23.
| Peroxisome proliferator-activated receptor gamma (PPARgamma) and its ligands: a review.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38XitFWmtLo%3D&md5=0ce50dcae1d711dfada85c52a340a218CAS | 11900961PubMed |
Hunter TE, Suster D, Dunshea FR, Cummins LJ, Egan AR, Leury BJ (2011) Dual energy X-ray absorptiometry (DXA) can be used to predict live animal and whole carcass composition of sheep. Small Ruminant Research 100, 143–152.
| Dual energy X-ray absorptiometry (DXA) can be used to predict live animal and whole carcass composition of sheep.Crossref | GoogleScholarGoogle Scholar |
Joosen AM, Bakker AH, Gering MJ, Westerterp KR (2006) The effect of the PPARgamma ligand rosiglitazone on energy balance regulation. Diabetes/Metabolism Research and Reviews 22, 204–210.
| The effect of the PPARgamma ligand rosiglitazone on energy balance regulation.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XlsFamu7Y%3D&md5=4146cf807b40d42f92cfebfd208cc90fCAS | 16110522PubMed |
Katz A, Nambi SS, Mather K, Baron AD, Follmann DA, Sullivan G, Quon MJ (2000) Quantitative insulin sensitivity check index: a simple, accurate method for assessing insulin sensitivity in humans. The Journal of Clinical Endocrinology and Metabolism 85, 2402–2410.
| Quantitative insulin sensitivity check index: a simple, accurate method for assessing insulin sensitivity in humans.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3cXlt1Wntrg%3D&md5=dde6c392a6c5cb2ccdf7fd31752f9398CAS | 10902785PubMed |
Kushibiki S, Hodate K, Shingu H, Ueda Y, Shinoda M, Mori Y, Itoh T, Yokomizo Y (2001) Insulin resistance induced in dairy steers by tumor necrosis factor alpha is partially reversed by 2,4-thiazolidinedione. Domestic Animal Endocrinology 21, 25–37.
| Insulin resistance induced in dairy steers by tumor necrosis factor alpha is partially reversed by 2,4-thiazolidinedione.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXmt1KltLk%3D&md5=0fd756dc8ee902884b78ff8332ff02e5CAS | 11524172PubMed |
Larsen TM, Toubro S, Astrup A (2003) PPARgamma agonists in the treatment of type II diabetes: is increased fatness commensurate with long-term efficacy? International Journal of Obesity and Related Metabolic Disorders 27, 147–161.
| PPARgamma agonists in the treatment of type II diabetes: is increased fatness commensurate with long-term efficacy?Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXhtFGhsrc%3D&md5=e41401755fd69d7fea5dd371df34966bCAS | 12586994PubMed |
McCann JP, Bergman EN, Beermann DH (1992) Dynamic and static phases of severe dietary obesity in sheep: food intakes, endocrinology and carcass and organ chemical composition. The Journal of Nutrition 122, 496–505.
McLaughlin JW (1992) The prime lamb program. Proceeding of the Australian Society of Animal Production 19, 173–175.
Pethick DW, Ball AJ, Banks RG, Hocquette JF (2011) Current and future issues facing red meat quality in a competitive market and how to manage continuous improvement. Animal Production Science 51, 13–18.
| Current and future issues facing red meat quality in a competitive market and how to manage continuous improvement.Crossref | GoogleScholarGoogle Scholar |
Petterson JA, Slepetis R, Ehrhardt RA, Dunshea FR, Bell AW (1994) Pregnancy but not moderate undernutrition attenuates insulin suppression of fat mobilization in sheep. The Journal of Nutrition 124, 2431–2436.
Robertson MW, Dunshea FR, Leury BJ (2009) Intravenous infusion of a lipid emulsion causes insulin resistance in Merino ewes under hyperinsulinemic-euglycaemic conditions. In ‘Ruminant physiology: digestion, metabolism and effects of nutrition on reproduction and welfare’. (Eds Y Chilliard, F Glasser, Y Foulconnier, F Bocquier, I Veissier, M Doreau) pp. 648–649. (Wageningen Academic Publishers: Wageningen, The Netherlands)
Saitoh Y, Liu R, Ueno H, Mizuta M, Nakazato M (2007) Oral pioglitazone administration increases food intake through ghrelin-independent pathway in Zucker fatty rat. Diabetes Research and Clinical Practice 77, 351–356.
| Oral pioglitazone administration increases food intake through ghrelin-independent pathway in Zucker fatty rat.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXovFKrs78%3D&md5=a61a6233b27ec04b7fef226fe25bab30CAS | 17321631PubMed |
Sechen SJ, Dunshea FR, Bauman DE (1990) Somatotropin in lactating cows: effect on response to epinephrine and insulin. The American Journal of Physiology 258, E582–E588.
Shimizu H, Tsuchiya T, Sato N, Shimomura Y, Kobayashi I, Mori M (1998) Troglitazone reduces plasma leptin concentration but increases hunger in NIDDM patients. Diabetes Care 21, 1470–1474.
| Troglitazone reduces plasma leptin concentration but increases hunger in NIDDM patients.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK1czpsVyktA%3D%3D&md5=94625926f2437da984305fdc7b267fcbCAS | 9727893PubMed |
Sillence MN (2004) Technologies for the control of fat and lean deposition in livestock. Veterinary Journal (London, England) 167, 242–257.
| Technologies for the control of fat and lean deposition in livestock.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD2c7oslCltw%3D%3D&md5=068f641268217b9635b52a3e2a4de1c5CAS |
Smith KL, Stebulis SE, Waldron MR, Overton TR (2007) Prepartum 2,4-thiazolidinedione alters metabolic dynamics and dry matter intake of dairy cows. Journal of Dairy Science 90, 3660–3670.
| Prepartum 2,4-thiazolidinedione alters metabolic dynamics and dry matter intake of dairy cows.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXot1OltL4%3D&md5=7c46f30ed2025de6f2d4a635f143f9baCAS | 17638977PubMed |
Smith KL, Butler WR, Overton TR (2009) Effects of prepartum 2,4-thiazolidinedione on metabolism and performance in transition dairy cows. Journal of Dairy Science 92, 3623–3633.
| Effects of prepartum 2,4-thiazolidinedione on metabolism and performance in transition dairy cows.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXptVWktb0%3D&md5=78e2a6308b4e51a730746d4c0da0e0c1CAS | 19620643PubMed |
Stanford K, Jones SDM, Price MA (1998) Methods of predicting lamb carcass composition: a review. Small Ruminant Research 29, 241–254.
| Methods of predicting lamb carcass composition: a review.Crossref | GoogleScholarGoogle Scholar |
Thatcher LP, Gaunt GM (1992) Effects of growth path and post slaughter chilling regime on carcass composition and meat quality of ewe lambs. Australian Journal of Agricultural Research 43, 819–830.
| Effects of growth path and post slaughter chilling regime on carcass composition and meat quality of ewe lambs.Crossref | GoogleScholarGoogle Scholar |
Tordjman J, Chauvet G, Quette J, Beale EG, Forest C, Antoine B (2003) Thiazolidinediones block fatty acid release by inducing glyceroneogenesis in fat cells. The Journal of Biological Chemistry 278, 18785–18790.
| Thiazolidinediones block fatty acid release by inducing glyceroneogenesis in fat cells.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXjvVSlur8%3D&md5=dbdd897a22849a423e33bd0ef1df02e0CAS | 12644461PubMed |
Verma NK, Singh J, Dey CS (2004) PPAR-gamma expression modulates insulin sensitivity in C2C12 skeletal muscle cells. British Journal of Pharmacology 143, 1006–1013.
| PPAR-gamma expression modulates insulin sensitivity in C2C12 skeletal muscle cells.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXhvFWltg%3D%3D&md5=64537f758d4ef47e574ce02be06ab390CAS | 15504754PubMed |
Warner RD, Ponnampalam EN, Kearney GA, Hopkins DL, Jacob RH (2007) Genotype and age at slaughter influence the retail shelf-life of the loin and knuckle from sheep carcasses. Australian Journal of Experimental Agriculture 47, 1190–1200.
| Genotype and age at slaughter influence the retail shelf-life of the loin and knuckle from sheep carcasses.Crossref | GoogleScholarGoogle Scholar |
Wolden-Hanson T, Marck BT, Matsumoto AM (2002) Troglitazone treatment of aging Brown Norway rats improves food intake and weight gain after fasting without increasing hypothalamic NPY gene expression. Experimental Gerontology 37, 679–691.
| Troglitazone treatment of aging Brown Norway rats improves food intake and weight gain after fasting without increasing hypothalamic NPY gene expression.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38XitFWlsLg%3D&md5=9957729989323084cd59f4a183b32c17CAS | 11909685PubMed |
