Hypothalamic ventricular ependymal thyroid hormone deiodinases are an important element of circannual timing in the siberian hamster (Phodopus sungorus)

Exposure to short days (SD) induces profound changes in the physiology and behaviour of Siberian hamsters, including gonadal regression and up to 30% loss in body weight. In a continuous SD environment after approximately 20 weeks, Siberian hamsters spontaneously revert to a long day (LD) phenotype, a phenomenon referred to as the photorefractory response. Previously we have identified a number of genes that are regulated by short photoperiod in the neuropil and ventricular ependymal (VE) cells of the hypothalamus, although their importance and contribution to photoperiod induced physiology is unclear. In this refractory model we hypothesised that the return to LD physiology involves reversal of SD expression levels of key hypothalamic genes to their LD values and thereby implicate genes required for LD physiology. Male Siberian hamsters were kept in either LD or SD for up to 39 weeks during which time SD hamster body weight decreased before increasing, after more than 20 weeks, back to LD values. Brain tissue was collected between 14 and 39 weeks for in situ hybridization to determine hypothalamic gene expression. In VE cells lining the third ventricle, expression of nestin, vimentin, Crbp1 and Gpr50 were down-regulated at 18 weeks in SD photoperiod, but expression was not restored to the LD level in photorefractory hamsters. Dio2, Mct8 and Tsh-r expression were altered by SD photoperiod and were fully restored, or even exceeded values found in LD hamsters in the refractory state. In hypothalamic nuclei, expression of Srif and Mc3r mRNAs was altered at 18 weeks in SD, but were similar to LD expression values in photorefractory hamsters. We conclude that in refractory hamsters not all VE cell functions are required to establish LD physiology. However, thyroid hormone signalling from ependymal cells and reversal of neuronal gene expression appear to be essential for the SD refractory response

Increased responses to the actions of fibroblast growth factor 21 on energy balance and body weight in a seasonal model of adiposity

The present study aimed to investigate the actions of fibroblast growth factor 21 (FGF21) on energy balance in a natural model of relative fatness, the Siberian hamster. Hamsters were studied under long days (LD) to promote weight gain, or short days to induce weight loss, and treated with rhFGF21 (3 mg/kg/day) via s.c. minipumps for 14 days. On days 7–9, detailed assessments of ingestive behaviour, metabolic gas exchange and locomotor activity were made. FGF21 caused substantial (P < 0.0001) weight loss in the fat LD state but not in the lean SD state: at the end of the study, FGF21-treated hamsters in LD lost 18% of body weight compared to vehicle controls, which is comparable to the natural body weight loss observed in SD. Epididymal fat pads, a correlate of total carcass fat content, were reduced by 19% in FGF21 treated hamsters in LD, whereas no difference was found in SD. Body weight loss in LD was associated with a reduction in food intake (P < 0.001) and a decreased respiratory exchange ratio (P < 0.001), indicating increased fat oxidation. Treatment with FGF21 maintained the normal nocturnal increase in oxygen consumption and carbon dioxide production into the early light phase in hamsters in LD, indicating increased energy expenditure, although locomotor activity was unaffected. These data suggest a greater efficacy of FGF21 in hamsters in LD compared to those in SD, which is consistent with both the peripheral and possibly central actions of FGF21 with respect to promoting a lean phenotype. The observed differences in FGF21 sensitivity may relate to day length-induced changes in adipose tissue mass

First refractory experiment body weight profiles.

<p>Body weights of Siberian hamsters that were kept in long days (LD) or short days (SD) for 18 weeks (LD18 black line, SD18 black dashed line), 25 weeks (LD25 blue line, SD25 blue dashed line), or 37 weeks (LD37 red line, SD37 red dashed line). Data are expressed as mean±SEM.</p

Type 2 and type 3 deiodinase gene expression in ventricular ependymal cells of switchback and refractory hamsters.

<p>Analysis and representative sections of (A) <i>Dio2</i> and (B) images of <i>Dio3</i> expression in the tanycytes of hamsters that had been kept in LD or SD for 14 weeksor 39 weeks, and hamsters that had been switched from SD to LD after 16 weeks and were culled after 22 weeks (SWB22) alongside an LD control group. Data are presented as means ± SEM and significance was defined as *p<0.05 and ***p<0.001. Images shown for <i>Dio2</i> expression are from the 14 week and 22 week housed hamsters. Images shown for <i>Dio3</i> expression are from the 14, 22 and 39 week housed hamsters.</p

Somatostatin and Melanocortin 3 receptor gene expression in hypothalamus.

<p>Analysis and representative sections of (A) <i>Srif</i> expression and (B) <i>Mc3r</i> expression in the arcuate nucleus (ARC) and (C) <i>Mc3r</i> expression in the ventromedial hypothalamus (VMH) of Siberian hamsters that had been kept in LD or SD photoperiod for 18, 25 or 37 weeks. Data are presented as means ± SEM. **p<0.01 and ***p<0.001.</p

Switchback and second refractory experiment body weight profiles.

<p>Body weights of Siberian hamsters that were kept in long days (LD) or short days (SD) for 14 weeks, 39 weeks. After 16 week a group of hamsters was switched from SD to LD (SWB22 blue dashed line) and culled alongside a control group () after 22 weeks. Data are expressed as mean±SEM.</p

Overview of the genes of neuronal (standard font) and ventricular ependymal cell (bold font) origin and their response to extended SD photoperiod exposure relative to their LD control groups.

<p>Arrows indicates direction and strength of change in gene expression: ↑ small, ↑↑ moderate and ↑↑↑ large increase in gene expression; ↓ small and ↓↓ moderate decrease in gene expression;  =  no change in gene expression; n/a gene expression was not available.</p

TSH receptor and nestin gene expression in ventricular ependymal cells of switchback and refractory hamsters.

<p>Analysis and representative sections of (A) <i>Tsh-r</i> and <i>nestin</i> (B) in the tanycytes of hamsters that had been kept in LD or SD for 14 weeks or 39 weeks, and hamsters that had been switched from SD to LD after 16 weeks and were culled after 22 weeks (SWB22) alongside an LD control group. Data are presented as means ± SEM and significance was defined as *p<0.05 and ***p<0.001.</p

Type 2 deiodinase and thyroid hormone transporter MCT8 expression in ventricular ependymal cells.

<p>Analysis and representative sections of (A) <i>Dio2</i> and (B) <i>Mct8</i> expression in the ependymal cells of Siberian hamsters that had been kept in LD or SD photoperiod for 18, 25 or 37 weeks. Expression was normalized to LD 18 week hamsters. Data are presented as means ± SEM and significance was defined as *p<0.05 and ***p<0.001.</p