Repercussions of hypo and hyperthyroidism on the heart circadian clock

Abstract

Myocardial gene expression and metabolism fluctuate over the course of the day in association with changes in energy supply and demand. Time-of-day-dependent oscillations in myocardial processes have been linked to the intrinsic cardiomyocyte circadian clock. Triiodothyronine (T3) is an important modulator of heart metabolism and function. Recently, our group has reported time-of-day-dependent rhythms in cardiac T3 sensitivity, as well as, T3-mediated acute alterations on core clock components. Hypo and hyperthyroidism are the second most prevalent endocrine disease worldwide. Considering the importance of the cardiomyocyte circadian clock and T3 to cardiac physiology, the aim of this study was to investigate the consequences of chronic hypo and hyperthyroidism on 24-h rhythms of circadian clock genes in the heart. Hypo and hyperthyroidism was induced in rats by thyroidectomy (Tx) and i.p. injections of supraphysiological dose of T3, respectively. Here we report alterations in mRNA levels of the major core clock components (Bmal1, Per2, Nr1d1 and Rora) for both experimental conditions (with the exception of Per2 during hyperthyroid condition). Oscillations in mRNA levels of key glucose and fatty acid metabolism genes known to be clock controlled (Pdk4, Ucp3, Acot1 and Cd36) were equally affected by the experimental conditions, especially during the hypothyroid state. These findings suggest that chronic alterations in thyroid status significantly impacts 24-h rhythms in circadian clock and metabolic genes in the heart. Whether these perturbations contribute towards the pathogenesis of cardiac dysfunction associated with hypo and hyperthyroidism requires further elucidation.

Circadian rhythm deregulation and thyroid dysfunction: results of an observational study on night shift workers

“…Thyroid receptors expression shows circadian variation in hepatocytes and adipose tissue in mice [17] and the interruption of this physiological rhythm is another possible mechanism to be considered when analysing the effect of sleep short duration and or misalignment. Some other experimental data supports that hypo and hyperthyroidism affect the clock genes tissue expression; for example, an experimental study showed a significant effect on myocardial metabolism related to the circadian rhythm [18].…”

Diurnal, metabolic and thermogenic alterations in a murine model of accelerated aging

“…Statistical analyses were performed using one-and twoway ANOVA, as well as repeated measures ANOVA, as described previously (Bray et al 2013(Bray et al , 2008Peliciari-Garcia et al 2018). Briefly, analyses were performed with Graph Pad Prism (GraphPad Software version 6.01, San Diego, CA, USA) to investigate the main effects of time and/or nutritional status, followed by Bonferroni post hoc analyses for pair-wise comparisons (indicated in Figures).…”

“…Briefly, analyses were performed with Graph Pad Prism (GraphPad Software version 6.01, San Diego, CA, USA) to investigate the main effects of time and/or nutritional status, followed by Bonferroni post hoc analyses for pair-wise comparisons (indicated in Figures). Cosinor analyses were performed for assessment of mesor (average value over a 24-h period), amplitude (peak-tomesor difference) and acrophase (timing of peak; ZT), as described previously (Peliciari-Garcia et al 2018). When appropriate, Student's t-test was also applied to these parameters.…”

Clock genes alterations and endocrine disorders

“…30 Although the circadian profile of TSH in humans is well documented, the underlying mechanism of such circadian regulation has not been explored. 32 31 The expression levels of the BMAL1 were upregulated in tissue samples of follicular (FTC) and papillary thyroid carcinoma (PTC), as compared with normal thyroid tissue and benign nodules, whereas CRY2 was downregulated in both FTC and PTC.…”

“…31 Either increased or decreased T3 levels regulated the expression of BMAL1 and ROR in rat cardiomyocytes, while only decreased T3 levels altered PER2 expression in rat cardiomyocytes. 32…”