Oxytocinergic Cells of the Hypothalamic Paraventricular Nucleus Are Involved in Food Entrainment

Abstract

When food is presented at a specific time of day subjects develop intense locomotor behavior before food presentation, termed food anticipatory activity (FAA). Metabolic and hormonal parameters, as well as neural structures also shift their rhythm according to mealtime. Food-entrained activity rhythms are thought to be driven by a distributed system of central and peripheral oscillators sensitive to food cues, but it is not well understood how they are organized for the expression of FAA. The hormone Oxytocin plays an important role in food intake, satiety and homeostatic glucose metabolism and although it is recognized that food is the main cue for food entrainment this hormone has not been implicated in FAA. Here we investigated the activity of oxytocinergic (OTergic) cells of the hypothalamus in relation to the timing of feeding in rabbit pups, a natural model of food entrainment. We found that OTergic cells of the supraoptic nucleus and the main body of the paraventricular nucleus (PVN) are activated after feeding which suggests that OT may be an entraining signal for food synchronization. Moreover, a detailed analysis of the PVN revealed that OTergic cells of the caudal PVN and a subpopulation in the dorsal part of the main body of this nucleus shows activation before the time of food but not 12 h later. Moreover this pattern persists in fasted subjects at the time of the previous scheduled time of nursing. The fact that those OTergic cells of the dorsal and caudal part of the PVN contain preautonomic cells that project to the adrenal, pancreas and liver perhaps may be related to the physiological changes in preparation for food ingestion, and synchronization of peripheral oscillators, which remains to be determined; perhaps they play a main role in the central oscillatory mechanism of FAA as their activity persists in fasted subjects at the time of the next feeding time.

Oxytocinergic Cells of the Posterior Hypothalamic Paraventricular Nucleus Participate in the Food Entrained Clock

“…In contrast to the previously well known activation of OT cells after food intake, recently we reported that a particular subpopulation of oxytocinergic cells in the posterior region of the paraventricular hypothalamus in the rabbit pup shows a clear activation in anticipation to their only daily episode of food ingestion 10 . Rabbit pups ingest food only once a day and had been recognized as a natural model of food entrainment 11,12 .…”

Circadian Rhythms of the Hypothalamus: From Function to Physiology

“…In spite of these findings the PVN still presents an attractive possibility for being part of the FEO. For example, oxytocin (OT) has recently been postulated as the main hormonal cue for FAA due to findings linking food entrainment in rabbits to OT-PVN neurons [119]. Although the SCN has direct projections to the PVN, the PVN neuroendocrine neurons are also indirectly modulated by the SCN via its innervation of the DMH, ARC and MPOA [120,121].…”

Food Entrainment, Arousal, and Motivation in the Neonatal Rabbit Pup

“… Spetter and Hallschmid, 2017 ; McCormack et al, 2020 ). However, in the main body of the PVN, specifically in its dorsal and ventral portion and in its caudal region, we found an activation of OT cells before milk ingestion in the rabbit ( Caba et al, 2020 ). In Figure 2 , we show this effect in the two subregions of the main body of the PVN.…”

“…In the rat under food restriction, and in the rabbit pup before their daily period of milk intake, there is an increase in corticosterone, free fatty acids and glucagon indicating a catabolic state, and in parallel there is a decrease in glycogen and insulin (Díaz-Muñoz et al, 2000;Escobar et al, 2000;Morgado et al, 2008Morgado et al, , 2010. We proposed (Caba et al, 2020) that the subpopulation of activated neurons A-F: Expression of oxytocin (white arrows) and double-labeled oxytocin and Fos (black arrows)-ir cells in the PVNmd (A,C,E) and PVNmv (B,D,F) just before nursing at 10:00 am (N10:00), 1.5 h after (N11:30) and in fasted subjects at the time of the previous scheduled nursing (F10:00). Note the increase in Fos/OT-ir cells before nursing (A) that persist in fasted subjects (E) only in the PVNmd.…”

“…In the rat under food restriction, and in the rabbit pup before their daily period of milk intake, there is an increase in corticosterone, free fatty acids and glucagon indicating a catabolic state, and in parallel there is a decrease in glycogen and insulin ( Díaz-Muñoz et al, 2000 ; Escobar et al, 2000 ; Morgado et al, 2008 , 2010 ). We proposed ( Caba et al, 2020 ) that the subpopulation of activated neurons in the PVN are related to these peripheral effects through identified preganglionic OT cells from the sympathetic and parasympathetic system that project from the PVN to the liver, pancreas, and adrenals ( Figure 1 , bottom panel; Buijs et al, 2001 , 2003 ). It seems likely that this activation is associated with both central and peripheral roles of these cells in the context of food entrainment.…”