Effect of exercise on photoperiod-regulated hypothalamic gene expression and peripheral hormones in the seasonal Dwarf Hamster Phodopus sungorus

Abstract

The Siberian hamster (Phodopus sungorus) is a seasonal mammal responding to the annual cycle in photoperiod with anticipatory physiological adaptations. This includes a reduction in food intake and body weight during the autumn in anticipation of seasonally reduced food availability. In the laboratory, short-day induction of body weight loss can be reversed or prevented by voluntary exercise undertaken when a running wheel is introduced into the home cage. The mechanism by which exercise prevents or reverses body weight reduction is unknown, but one hypothesis is a reversal of short-day photoperiod induced gene expression changes in the hypothalamus that underpin body weight regulation. Alternatively, we postulate an exercise-related anabolic effect involving the growth hormone axis. To test these hypotheses we established photoperiod-running wheel experiments of 8 to 16 weeks duration assessing body weight, food intake, organ mass, lean and fat mass by magnetic resonance, circulating hormones FGF21 and insulin and hypothalamic gene expression. In response to running wheel activity, short-day housed hamsters increased body weight. Compared to short-day housed sedentary hamsters the body weight increase was accompanied by higher food intake, maintenance of tissue mass of key organs such as the liver, maintenance of lean and fat mass and hormonal profiles indicative of long day housed hamsters but there was no overall reversal of hypothalamic gene expression regulated by photoperiod. Therefore the mechanism by which activity induces body weight gain is likely to act largely independently of photoperiod regulated gene expression in the hypothalamus.

Figure 1. The effect of running wheel activity on body weight.

A) Mean body mass (g) of adult male Siberian hamsters during an 8 week exposure to short day (SD) or long day (LD) photoperiod with or without access to a running wheel (n = 7 per group). * SD-C significantly different vs SD-RW (P<0.05 or lower). B) 16 week photoperiod exposure (n = 6–9 per group) ^a SD-C significantly different to the other 3 groups (P<0.05 or lower). # Significantly different from LD-RW group (P<0.05).

Figure 2. The effect of running wheel activity on fat and lean mass.

(A) Fat mass of Siberian hamsters held in photoperiod for 8 weeks; (B) Lean mass of Siberian hamsters held in photoperiod for 8 weeks; (C) Fat mass of Siberian hamsters held in photoperiod for 16 weeks; (D) Lean mass of Siberian hamsters held in photoperiod for 16 weeks (n = 6–9 per group). *P<0.05; **P<0.01; ***P<0.001. LD-RW, long days with running wheel access; LD-C, long days without running wheel access; SD-RW, short days with running wheel access; SD-C, short day without running wheel access.

Figure 3. The effect of running wheel activity on organ mass.

(A) Liver, (B) heart, (C) kidney, (D) paired testes, (E) right epididymal fat pad of adult male Siberian hamsters after 8 (filled bars) or 16 week (open bars) exposure to long day (LD) or short day (SD) photoperiod with (RW) or without (C) a running wheel (n = 6 per group 8 weeks or 6–9 per group 16 weeks). Relevant significant differences are shown *P<0.05, **P<0.01, ***P<0.001.

Figure 4. Liver glucose and fat content of adult male Siberian hamsters after 8 weeks exposure to short day (SD) photoperiod or long day (LD) photoperiod or with (RW) or without (C) a running wheel (n = 6 in each group).

Results show means ± SEM (#P<0.05, with respect to an overall effect of photoperiod).

Figure 5. Messenger RNA expression of genes involved in regulation and transport of thyroid hormone.

Quantification of (A) type 2 (Dio2) and (B) type 3 deiodinase (Dio3) mRNA expression in the 3rd ventricular tanycyte layer of adult Siberian hamsters (C) thyroid releasing hormone (Trh) mRNA expression in the paraventricular nucleus (PVN) and (D) monocarboxylate transporter 8 (Mct8), Hamsters were kept 8 weeks in long day (LD) photoperiod or short day (SD) photoperiod or with (RW) or without (C) a running wheel (n = 6 in each group except Dio2 where n = 5–7 per group). Results shown are means+SEM. The LD-C group was set to 100% expression value (except for Dio3, SD-C set at 100%) and other treatment values were calculated accordingly. Relevant significant differences are shown (###P<0.001, ##P<0.01 with respect to overall difference between photoperiod; *<P0.05 with respect to post-hoc analysis of differences between groups; ns not significant).

Figure 6. Messenger RNA expression of photoperiod-regulated genes in the ventricular ependymal cells.

Quantification of (A) Vimentin and (B) G-protein-coupled receptor 50 (Gpr50) mRNA expression. Adult male Siberian hamsters were exposed to long day (LD) photoperiod or short day (SD) photoperiod or with (RW) or without (C) a running wheel for 8 weeks (n = 6–7 in each group). The LD-C group was set to 100% expression value and other treatment values were calculated accordingly. Results show means ± SEM (*P<0.05).

Figure 7. Quantification of Vgf mRNA expression in the hypothalamic dorsal medial posterior ARC (dmpARC).

Adult male Siberian hamsters were exposed to long day (LD) photoperiod or short day (SD) photoperiod or with (RW) or without (C) a running wheel access for 8 weeks (n = 4–6 in each group). The SD-RW group was set to 100% expression value and other treatment values were calculated accordingly. Results show means+SEM (###P<0.001 with respect to overall difference between photoperiod; ** P<0.01 and *, P<0.05 with respect to post-hoc analysis of differences between groups).

Figure 8. Messenger RNA expression of genes involved in homeostatic mechanisms of appetite and energy balance.

Quantification of (A) agouti-related protein (Agrp), (B) neuropeptide Y (Npy), (C) cocaine- and amphetamine-regulated transcript (Cart) and (D) proopiomelanocortin (Pomc) mRNA expression in the hypothalamic arcuate nucleus (ARC) of adult male Siberian hamsters after 8 weeks exposure to long day (LD) photoperiod or short day (SD) photoperiod with (RW) or without (C) a running wheel (N = 6 in each group). (E) Proopiomelanocortin (Pomc) mRNA expression in the hypothalamic arcuate nucleus (ARC) after 12 weeks exposure to long day (LD) photoperiod or short day (SD) photoperiod or with (RW) or without (C) a running wheel (n = 5–6 in each group). The LD-C group was set to 100% expression value and other treatment values were calculated accordingly. Results show means+SEM (##P<0.01, #P<0.05 with respect to an overall effect of photoperiod; *P<0.05, **P<0.01, ***P<0.001, with respect to post-hoc analysis of differences between groups).

Figure 9. Quantification of somatotropin release-inhibiting factor (Srif) mRNA expression in the hypothalamic arcuate nucleus (ARC).

Adult male Siberian hamsters were exposed to long day (LD) or short day (SD) photoperiod or with (RW) or without (C) a running wheel for 8 weeks (n = 5–6 in each group). Values are means ± SEM. The SD-C group was set to 100% expression value and other treatment values were calculated accordingly ( ###P<0.001 with respect to an overall effect of photoperiod; *; P<0.05 with respect to post-hoc analysis between groups).

Figure 10. Effect of photoperiod and running wheel activity on circulating concentrations of (A) insulin, (B) FGF21 in adult male Siberian hamsters maintained in long days (LD) or short days (SD) with (RW) or without a (C) running wheel for 12 weeks (LD-RW n = 10, LD-C n = 10, SD-RW n = 9, SD-C n = 8).

Values are the mean+SEM (###P<0.001, ##P<0.01 with respect to overall effect of photoperiod or activity; *P<0.05, **P<0.01 with respect to post-hoc analysis between groups).