ECE2017 Oral Communications Receptors & Signalling (5 abstracts)
Recent findings revealed 3,5-diiodo-L-thyronine (3,5-T2) as a metabolically active iodothyronine affecting hepatic energy and lipid metabolism. Therefore, 3,5-T2 has been proposed as a potential hypolipidemic agent for treatment of obesity and its hepatic aftermath. So far only limited data exists relating to the effects of 3,5-T2 on metabolism in euthyroid mammals maintained on high-fat diet from the day of weaning onwards. Therefore, we performed a study in which 20-week old diet-induced obese male mice in comparison to lean animals received either 3,5-T2 (2.5 μg/g body weight) or saline over a four-week period. To identify new target genes and signaling mechanisms of 3,5-T2 which are distinct from established hepatic T3 action we performed microarray-based transcriptome analyses of liver tissue. The transcriptome as well as qPCR data demonstrated higher hepatic expression of genes involved in cholesterol biosynthesis (e.g. Sqle 4.8-fold, Cyp51 2.8-fold, Hsd17b7 1.8-fold) and bile acid formation (Cyp7a1 2.0-fold, Cyp39a1 2.9-fold) in obese but not in lean mice treated with 3,5-T2. In contrast to the elevation of hepatic cholesterol biosynthesis, serum cholesterol concentration was reduced by up to 57% with 3,5-T2 administration. In addition, 3,5-T2 modulated expression of genes important for sex steroid biosynthesis and inactivation (e.g. Cyp17a1 3.5-fold, Hsd17b6 -7.8-fold). GC MS/MS analysis of the hepatic sex steroid hormone profile indicated higher progesterone and androstenedione content in livers of obese mice treated with 3,5-T2, whereas no such changes were observed in 3,5-T2-treated lean mice. These results suggest a diet-dependent role of 3,5-T2 in modulating local cholesterol as well as sex steroid biosynthesis and androgen homeostasis in mouse liver. Such actions of thyroid hormone metabolites have not been reported elsewhere up to date and might help to explain liver-targeting effects of T3-receptor beta-selective ligands.
20 May 2017 - 23 May 2017