A novel regulator of thirst behavior: phoenixin.

There are examples of physiological conditions under which thirst is inappropriately exaggerated, and the mechanisms for these paradoxical ingestive behaviors remain unknown. We are interested in thirst mechanisms across the female life cycle and have identified a novel mechanism through which ingestive behavior may be activated. We discovered a previously unrecognized endogenous hypothalamic peptide, phoenixin (PNX), identified physiologically relevant actions of the peptide in brain and pituitary gland to control reproductive hormone secretion in female rodents, and in the process identified the previously orphaned G protein-coupled receptor Gpr173 to be a potential receptor for the peptide. Labeled PNX binding distribution in brain parallels areas known to be important in ingestive behaviors as well in areas where gonadal steroids feedback to control estrous cyclicity (Stein LM, Tullock CW, Mathews SK, Garcia-Galiano D, Elias CF, Samson WK, Yosten GLC, Am J Physiol Regul Integr Comp Physiol 311: R489-R496, 2016). We have demonstrated upregulation of Gpr173 during puberty, fluctuations across the estrous cycle, and, importantly, upregulation during the last third of gestation. It is during this hypervolemic, hyponatremic state that both vasopressin secretion and thirst are inappropriately elevated in humans. Here, we show that central administration of PNX stimulated water drinking in both males and females under ad libitum conditions, increased water drinking after overnight fluid deprivation, and increased both water and 1.5% NaCl ingestion under fed and hydrated conditions. Importantly, losartan pretreatment blocked the effect of PNX on water drinking, and knockdown of Gpr173 by use of short interfering RNA constructs significantly attenuated water drinking in response to overnight fluid deprivation. These actions, together with the stimulatory action of PNX on vasopressin secretion, suggest that this recently discovered neuropeptide may impact the recruitment of critically important neural circuits through which ingestive behaviors and endocrine mechanisms that maintain fluid and electrolyte homeostasis are regulated.

Neonatal nutritional programming induces gliosis and alters the expression of T-cell protein tyrosine phosphatase and connexins in male rats.

Changes to neonatal nutrition result in long-lasting impairments in energy balance, which may be described as metabolic programing. Astrocytes, which are interconnected by gap junctions, have emerged as important players in the hypothalamic control of food intake. In order to study the effects of nutritional programming on glial morphology and protein expression, cross-fostered male Wistar rats at postnatal day 3 were assigned to three groups based on litter size: small litter (3 pups per dam, SL), normal litter (10 pups per dam, NL), and large litter (16 pups per dam, LL). Rats from the SL group exhibited higher body weight throughout the study and hyperphagia after weaning. LL animals exhibited hyperphagia, high energy efficiency and catch-up of body weight after weaning. Both the SL and LL groups at postnatal day 60 (PN60) exhibited increased levels of plasma leptin, the Lee index (as an index of obesity), adiposity content, immunoreactivity toward T-cell protein tyrosine phosphatase (TCPTP), and glial fibrillary acidic protein (GFAP) in the arcuate nucleus (ARC) of the hypothalamus. Astrocyte morphology was altered in the ARC of SL and LL animals, and this effect occurred in parallel with a reduction in immunoreactivity toward connexin 30 (CX30). The data obtained demonstrate that both neonatal over- and underfeeding promote not only alterations in the metabolic status but also morphological changes in glial cells in parallel with increasing TCPTP and changes in connexin expression.