Rosiglitazone maleate increases weight gain and body fat content in growing lambs

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.