Hypothalamic Wnt Signalling and its Role in Energy Balance Regulation

Wnt signalling and its downstream effectors are well known for their role in embryogenesis and tumorigenesis; regulating cell proliferation, survival and differentiation. In the nervous system Wnt signalling has been described mainly during embryonic development, but accumulating evidence suggests that it also plays a major role in the adult brain morphogenesis and function. Studies have predominantly concentrated on memory formation of the hippocampus, but recent data indicate that Wnt signalling is also critical for the neuroendocrine control of the developed hypothalamus, a brain centre that is key in energy balance regulation and whose dysfunction is implicated in metabolic disorders such as type 2 diabetes and obesity. Based on scattered findings that reported the presence of Wnt molecules in the tanycytes and ependymal cells lining the third ventricle and arcuate nucleus neurons of the hypothalamus, the potential importance in key regions of food intake and body weight regulation has been investigated in recent studies. The purpose of this review is to bring together the current knowledge on Wnt signalling in the hypothalamus of adult animals and discuss evidence demonstrating a key role for members of the Wnt signalling family in glucose and energy balance regulation in the hypothalamus in diet induced and genetically obese (leptin deficient) mice. Aspects of Wnt signalling in seasonal (photoperiod sensitive) rodents will also be highlighted, given that recent evidence indicates that the Wnt pathway in the hypothalamus is not only regulated by diet and leptin but also by photoperiod in seasonal animals, which is connected to natural adaptive changes in food intake and body weight. Thus Wnt signalling seems to be critical as a modulator for normal functioning of the physiological state in the healthy adult brain, and crucial for normal glucose and energy homeostasis where its dysregulation can lead to a range of metabolic disorders.