The purpose of this experiment was to determine the relationship between lipid metabolism and the expression of specific genes in chickens fed
methimazole to produce
hypothyroidism. Male, broiler chickens growing from 14 to 28 days of age were fed diets containing 18% crude
protein and either 0 or 1 g
methimazole per kg of diet. At 28 days, these two groups were further subdivided into groups receiving 18% crude
protein diets containing either 0 or 1 mg
triiodothyronine (T(3)) per kg. Birds were sampled at intervals from 0 to 120 h. Measurements taken included in vitro lipogenesis (IVL), malic
enzyme (ME),
isocitrate dehydrogenase (ICD-
NADP),
aspartate aminotransferase (AAT) activities and the expression of the genes for ME,
fatty acid synthase (FAS),
NADP-ICD, AAT and acetyl
coenzyme carboxylase (ACC). Gene expression was estimated with real time RT-PCR assays. Expression rates were noted as C(t)'s. Dietary
methimazole decreased IVL and ME at 28 days of age. T(3) and supplementation for 1 day restored both IVL and ME. Paradoxically, continuing T(3) replenishment for a longer period decreased IVL without affecting ME activity. Although
methimazole decreased ME gene expression, there was only a transitory relationship between
enzyme activity and gene expression when plasma T(3) was replenished with exogenous T(3). These data explain the apparent dichotomies in lipid metabolism elicited by changes in the thyroid state of animals. Most metabolic changes in response to feeding T(3) occurred within a short period of time, suggesting that changes in intermediary metabolism preceded morphological changes. Furthermore, the thyroid state of the animal will determine responses to exogenous T(3).