title: Loss of acute satiety response to cholecystokinin in pregnant rats.
abstract: During pregnancy, food intake and fat mass are increased to meet the energy demands of the growing conceptus and to prepare for the subsequent demands of lactation. A state of leptin resistance develops during pregnancy in the rat, which can facilitate the increase in food intake despite pregnancy-induced increases in leptin concentrations. Cholecystokinin (CCK) is a satiety factor that is released from the gut during feeding and acts to terminate short-term food intake. Circulating leptin concentrations can modulate the anorexic response to CCK; low leptin concentrations decrease the potency of CCK to reduce food intake. Because rats are leptin resistant by day 14 of pregnancy, it was hypothesised that the feeding response to CCK would be attenuated at that time. Nonpregnant and day 14 pregnant rats received an i.p. injection of CCK-8 (3 μg/kg body weight) or vehicle directly before the start of the dark phase. Food intake was measured 30 min after lights out. Approximately 90 min after receiving either CCK-8 or vehicle, rats were transcardially perfused with 4% paraformaldehyde. Food intake was significantly decreased in CCK-treated nonpregnant rats, although similar treatment did not reduce food intake in day 14 pregnant rats. CCK treatment lead to significant increased in c-Fos expression in the nucleus of the solitary tract (NTS) in both nonpregnant and pregnant rats compared to vehicle treatment, although the number of CCK-induced c-Fos positive cells was significantly less in pregnant rat compared to nonpregnant rats. Although CCK treatment increased the number of c-Fos positive cells in the hypothalamic paraventricular nucleus and supraoptic nucleus in nonpregnant rats, no significant increase was observed in these areas during pregnancy. These results indicate that pregnant rats are no longer responsive to the actions of CCK on short-term food intake and that CCK action in the NTS is reduced during pregnancy.
authors.affiliation: Centre for Neuroendocrinology and Department of Anatomy, University of Otago, Dunedin, New Zealand. sharon.ladyman@anatomy.otago.ac.nz
authors.forename: S R
authors.initials: SR
authors.lastname: Ladyman
authors.forename: T J
authors.initials: TJ
authors.lastname: Sapsford
authors.forename: D R
authors.initials: DR
authors.lastname: Grattan
mesh_terms: D000818:Animals; D001933:Brain Stem / Q000187:drug effects / Q000378:metabolism; D002766:Cholecystokinin / Q000494:pharmacology*; D005247:Feeding Behavior / Q000187:drug effects; D005260:Female; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D011247:Pregnancy; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D012528:Satiety Response / Q000187:drug effects*
chemical_list: D016760:Proto-Oncogene Proteins c-fos; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; D002766:Cholecystokinin