A role for VGF in the hypothalamic arcuate and paraventricular nuclei in the control of energy homeostasis.

The arcuate nucleus is the main receptive area of the brain for peripheral and central metabolic cues and its integrity is essential for the maintenance of energy homeostasis. In the arcuate nucleus, different neuronal populations process metabolic signals and transmit this information to other nuclei of the hypothalamus by means of neurotransmitters and a combination of neuropeptides whose expression is modulated by the nutritional status. Here we investigated the changes in expression and synthesis of the polypeptide VGF in the arcuate nucleus of rats, in relation to the two main categories of neurons that show colocalization with VGF: the orexigenic NPY-expressing cells and the anorexigenic POMC-expressing cells. The results show that fasting is the most important stimulus for VGF expression, and that the up-regulation of VGF mRNA is restricted to the NPY area of the arcuate nucleus. POMC neurons express VGF under all feeding conditions, but especially in ad libitum-fed and fasted-refed animals. We also show that VGF arcuate neurons project to the pre-autonomic neurons of the paraventricular nucleus of the hypothalamus, providing anatomical evidence suggesting VGF as a central modulator of the autonomic nervous system.

The suprachiasmatic nucleus changes the daily activity of the arcuate nucleus α-MSH neurons in male rats.

Timing of metabolic processes is crucial for balanced physiology; many studies have shown the deleterious effects of untimely food intake. The basis for this might be an interaction between the arcuate nucleus (ARC) as the main integration site for metabolic information and the suprachiasmatic nucleus (SCN) as the master clock. Here we show in male rats that the SCN influences ARC daily neuronal activity by imposing a daily rhythm on the α-MSH neurons with a peak in neuronal activity at the end of the dark phase. Bilateral SCN lesions showed a complete disappearance of ARC neuronal rhythms and unilateral SCN lesions showed a decreased activation in the ARC at the lesioned side. Moreover light exposure during the dark phase inhibited ARC and α-MSH neuronal activity. The daily inhibition of ARC neuronal activity occurred in light-dark conditions as well as in dark-dark conditions, demonstrating the inhibitory effect to be mediated by increased SCN (subjective) day neuronal activity. Injections into the SCN with the neuronal tracer cholera toxin B showed that α-MSH neurons receive direct projections from the SCN. The present study demonstrates that the SCN activates and possibly also inhibits depending on the moment of the circadian cycle ARC α-MSH neurons via direct neuronal input. The persistence of these activity patterns in fasted animals demonstrates that this SCN-ARC interaction is not necessarily satiety associated but may support physiological functions associated with changes in the sleep-wake cycle.

The NPY intergeniculate leaflet projections to the suprachiasmatic nucleus transmit metabolic conditions.

The intergeniculate leaflet (IGL) is classically known as the area of the Thalamic Lateral Geniculate Complex providing the suprachiasmatic nucleus (SCN) non-photic information. In the present study we investigated whether this information might be related to the metabolic state of the animal. The following groups of male Wistar rats were used for analysis of neuropeptide Y (NPY) and c-Fos in the IGL and SCN. (1) Fed ad libitum. (2) Fasted for 48 h. (3) Fasted for 48 h followed by refeeding for 3 h. (4) Monosodium glutamate-lesioned and 48 h fasted. (5) Electrolytic lesion in the IGL and 48 h fasted. The results were quantified by optical densitometry. Neuronal tracers were injected in two brain areas that receive metabolic information from the periphery, the arcuate nucleus (ARC) and Nucleus of the Tractus Solitarius to investigate whether there is an anatomical relationship with the IGL. Lesion studies showed the IGL, and not the ARC, as origin of most NPY projections to the SCN. Fasting induced important changes in the NPY expression in the IGL, coinciding with similar changes of NPY/glutamate decarboxylase projections of the IGL to the SCN. These changes revealed that the IGL is involved in the transmission of metabolic information to the SCN. In fasted animals IGL lesion resulted in a significant increase of c-Fos in the SCN as compared to intact fasted animals demonstrating the inhibitory influence of the IGL to the SCN in fasting conditions. When the animal after fasting was refed, an increase of c-Fos in the SCN indicated a removal of this inhibitory input. Together these observations show that in addition to increased inhibitory IGL input during fasting, the negative metabolic condition also results in increased excitatory input to the SCN via other pathways. Consequently the present observations show that at least part of the non-photic input to the SCN, arising from the IGL contains information about metabolic conditions.