Photoperiodic and diurnal regulation of WNT signalling in the arcuate nucleus of the female Djungarian hamster, Phodopus sungorus

The WNT pathway was shown to play an important role in the adult central nervous system. We previously identified the WNT pathway as a novel integration site of the adipokine leptin in mediating its neuroendocrine control of metabolism in obese mice. Here, we investigated the implication of WNT signalling in seasonal body weight regulation exhibited by the Djungarian
hamster (Phodopus sungorus), a seasonal mammal that exhibits profound annual changes in leptin sensitivity. We furthermore investigated whether crucial components of the WNT pathway are regulated in a diurnal manner. Gene expression of key components of the WNT pathway in the hypothalamus of hamsters acclimated to either long day (LD) or short day (SD) photoperiod was
analysed by in-situ hybridization. We detected elevated expression of the genes WNT-4, Axin-2, Cyclin-D1 and SFRP-2, in the hypothalamic arcuate nucleus, a key energy balance integration site, during LD compared with SD, as well as a diurnal regulation of Axin-2, Cyclin-D1 and DKK-3. Investigating the effect of photoperiod as well as leptin on the activation (phosphorylation) of the
WNT co-receptor LRP-6-(Ser1490) by immunohistochemistry, we found elevated activity in the arcuate nucleus during LD relative to SD, as well as after leptin treatment (2 mg/kg body weight). These findings indicate that differential WNT signalling may be associated with seasonal body weight regulation and is partially regulated in a diurnal manner in the adult brain. Furthermore,
they suggest that this pathway plays a key role in the neuroendocrine regulation of body weight and integration of the leptin signal.