Session: FP34-Molecular Mechanisms in Thyroid Hormone Action & Cancer
Room 103 (Moscone Center)
Poster Board MON-416
Both body weight and hormonal profiling during the 8-week diet treatment confirmed the reported resistance to DIO and low T4 in WSB/EiJ compared to C57BL/6J mice. In particular, T3:T4 ratios were stable in C57BL/6J mice on all diets whereas they increased in HFD fed WSB/EiJ, reflecting adaptability of the hypothalamo-pituitary-thyroid axis (HPT) in WSB/EiJ mice. Control of TH availability is being characterised by deiodinase activity assays in different tissues.
Indirect calorimetry showed that HFD-treated WSB/EiJ mice remain resistant to DIO, despite moving less and eating more. In addition, control fed WSB/EiJ mice displayed a strong circadian substrate-switching capacity that was dampened, but maintained, under HFD. Remarkably, WSB/EiJ mice switched from strict lipid usage at ZT8, to high carbohydrate oxidation during the feeding period, even achieving de novo lipogenesis. This shift in substrate usage was confirmed by greater glucose tolerance of WSB/EiJ than C57BL/6J at ZT1, an effect that was inverted at ZT8.
To investigate mitochondrial roles in the differential metabolic responses, we used mitochondrial respiration analyses (Seahorse Bioscience) and transmission electron microscopy (TEM). Transcriptomic analysis (RNAseq) on RNA from laser capture microdissected hypothalamic paraventricular nucleus (PVN) is being exploited to compare gene networks involved in central regulation of metabolism in the two strains.
The whole-body characterisation and large-scale transcriptomic analyses in our study will provide a better understanding of the mechanisms underlying the links between TH set-points and central control of metabolism. We propose that the reported extreme longevity of WSB/EiJ mice (2) could be linked to the TH-associated metabolic plasticity of this strain.
Nothing to Disclose: JB, JT, IS, RD, SL, MSC, BD
*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm
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