High-Sugar, but Not High-Fat, Food Activates Supraoptic Nucleus Neurons in the Male Rat

Abstract

Oxytocin is a potent anorexigen and is believed to have a role in satiety signaling. We developed rat models to study the activity of oxytocin neurons in response to voluntary consumption or oral gavage of foods using c-Fos immunohistochemistry and in vivo electrophysiology. Using c-Fos expression as an indirect marker of neural activation, we showed that the percentage of magnocellular oxytocin neurons expressing c-Fos increased with voluntary consumption of sweetened condensed milk (SCM). To model the effect of food in the stomach, we gavaged anesthetized rats with SCM. The percentage of supraoptic nucleus and paraventricular nucleus magnocellular oxytocin-immunoreactive neurons expressing c-Fos increased with SCM gavage but not with gastric distention. To further examine the activity of the supraoptic nucleus, we made in vivo electrophysiological recordings from SON neurons, where anesthetized rats were gavaged with SCM or single cream. Pharmacologically identified oxytocin neurons responded to SCM gavage with a linear, proportional, and sustained increase in firing rate, but cream gavage resulted in a transient reduction in firing rate. Blood glucose increased after SCM gavage but not cream gavage. Plasma osmolarity and plasma sodium were unchanged throughout. We show that in response to high-sugar, but not high-fat, food in the stomach, there is an increase in the activity of oxytocin neurons. This does not appear to be a consequence of stomach distention or changes in osmotic pressure. Our data suggest that the presence of specific foods with different macronutrient profiles in the stomach differentially regulates the activity of oxytocin neurons.

The osmoresponsiveness of oxytocin and vasopressin neurones: Mechanisms, allostasis and evolution

“…Interestingly, however, they are inhibited by gavage of isocaloric cream 119. 111,114,115 The effects of CCK 116 and probably those of secretin too are mediated by activation of gastric vagal afferents that lead to activation of neurones in the nucleus tractus solitarii (NTS), 117 including the noradrenergic A2 cells that project directly to oxytocin cells.…”

Neural connectivity between the hypothalamic supramammillary nucleus and appetite‐ and motivation‐related regions of the rat brain

“…The hypothalamic neurohormone oxytocin has an emerging role in appetite control, and may be involved specifically in an anorexigenic response to carbohydrate intake . Oxytocin may have a neuromodulatory role in the SuM, and we have previously shown that gavage of a high‐sugar food increases the electrical activity of oxytocin neurones in the rat supraoptic nucleus, which may lead to somatodendritic oxytocin release to target the SuM. Alternatively or additionally, ghrelin signalling may be relevant.…”

“…Brains were processed for Fos and TH‐like immunoreactivity, imaged and quantified as described previously . To detect Fos‐like immunoreactivity, we used anti‐Fos rabbit primary antibody (dilution 1:100 000; 226 003; Synaptic Systems, Göttingen, Germany) and a biotinylated horse anti‐rabbit immunoglobulin (Ig)G secondary antibody (dilution 1:500; BA‐1100; Vector Laboratories, Burlingame, CA, USA).…”

“…600 µL kg ‐1 , administered i.p.) and processing brain sections as described . Dense Fos+ staining was observed in osmosensitive brain regions, including the supraoptic and paraventricular nucleus of the hypothalamus.…”

The Anorexigenic Neural Pathways of Oxytocin and Their Clinical Implication

“…Oxytocin plays an important role in the termination of food intake, and oxytocin neurons are activated following food consumption or ingestion [41,42]. Hypothalamic oxytocin mRNA expression is reduced with fasting and recovers with refeeding [43] or the administration of leptin [44].…”