The effect of maternal period nutritional status on oro-sensorial fat perception and taste preference in rats.

CD36 and GPR120 play an important role in the perception and preference for fat-rich food consumption. We aimed to investigate the relationship between oro-gustatory perception of lipids, fatty taste preference, and maternal (Gestation + Lactation)-maturation period nutrition status in offspring Sprague-Dawley rats. In our study, mother rats were fed with control (C) or high-fat diets (HFD) during gestation (21 days) and lactation (21 days) periods. After weaning, the offspring were fed with control (C) or high-fat diets (HFD) during the maturation (120 days) period. Daily calorie intake and weekly body weight measurements were monitored. Two-bottle preference (TBPT) and licking tests measured the fat perceptions and preferences. Plasma levels of insulin, leptin, glucose, and triglyceride were measured. The protein and mRNA expressions of CD36 and GPR120 in the circumvallate papillae (CVP) were determined. The 48 h TBPT results revealed that maternal HFD-exposed offspring rats significantly preferred 2% rapeseed oil solution regardless of the type of maturation diet. According to the licking test, C/C group (C diet exposed group in maternal and maturation periods) offspring licked 0.1% oleic acid-containing water more than C/HFD (C diet exposed in maternal period and HFD exposed group in maturation period) and HFD/HFD group. (HFD exposed group in maternal and maturation periods) groups. Plasma insulin and leptin concentrations significantly increased in HFD/HFD groups compared to C/C group. CD36 protein expressions were significantly lower in HFD/HFD than C/HFD and HFD/C groups. GPR120 and GNAT3 mRNA expressions in HFD/C group were significantly higher than in C/HFD group. Our results suggest that HFD exposure during maternal and maturation period may play a role in fat perception/preference through oral lipid sensors.

Inactivation of Magel2 suppresses oxytocin neurons through synaptic excitation-inhibition imbalance.

Prader-Willi and the related Schaaf-Yang Syndromes (PWS/SYS) are rare neurodevelopmental disorders characterized by overlapping phenotypes of high incidence of autism spectrum disorders (ASD) and neonatal feeding difficulties. Based on clinical and basic studies, oxytocin pathway defects are suggested to contribute disease pathogenesis but the mechanism has been poorly understood. Specifically, whether the impairment in oxytocin system is limited to neuropeptide levels and how the functional properties of broader oxytocin neuron circuits affected in PWS/SYS have not been addressed. Using cell type specific electrophysiology, we investigated basic synaptic and cell autonomous properties of oxytocin neurons in the absence of MAGEL2; a hypothalamus enriched ubiquitin ligase regulator that is inactivated in both syndromes. We observed significant suppression of overall ex vivo oxytocin neuron activity, which was largely contributed by altered synaptic input profile; with reduced excitatory and increased inhibitory currents. Our results suggest that dysregulation of oxytocin system goes beyond altered neuropeptide expression and synaptic excitation inhibition imbalance impairs overall oxytocin pathway function.

Effects of chronic high fat diet on mediobasal hypothalamic satiety neuron function in POMC-Cre mice.

OBJECTIVE: The prevalence of obesity has increased over the past three decades. Proopiomelanocortin (POMC) neurons in the hypothalamic arcuate nucleus (ARC) play a vital role in induction of satiety. Chronic consumption of high-fat diet is known to reduce hypothalamic neuronal sensitivity to hormones like leptin, thus contributing to the development and persistence of obesity. The functional and morphological effects of a high-calorie diet on POMC neurons and how these effects contribute to the development and maintenance of the obese phenotype are not fully understood. For this purpose, POMC-Cre transgenic mice model was exposed to high-fat diet (HFD) and at the end of a 3- and 6-month period, electrophysiological and morphological changes, and the role of POMC neurons in homeostatic nutrition and their response to leptin were thoroughly investigated. METHODS: Effects of HFD on POMC-satiety neurons in transgenic mice models exposed to chronic high-fat diet were investigated using electrophysiological (patch-clamp), chemogenetic and Cre recombinase advanced technological methods. Leptin, glucose and lipid profiles were determined and analyzed. RESULTS: In mice exposed to a high-fat diet for 6 months, no significant changes in POMC dendritic spine number or projection density from POMC neurons to the paraventricular hypothalamus (PVN), lateral hypothalamus (LH), and bed nucleus stria terminalis (BNST) were observed. It was revealed that leptin hormone did not change the electrophysiological activities of POMC neurons in mice fed with HFD for 6 months. In addition, chemogenetic stimulation of POMC neurons increased HFD consumption. In the 3-month HFD-fed group, POMC activation induced an orexigenic response in mice, whereas switching to a standard diet was found to abolish orexigenic behavior in POMC mice. CONCLUSIONS: Chronic high fat consumption disrupts the regulation of POMC neuron activation by leptin. Altered POMC neuron activation abolished the neuron's characteristic behavioral anorexigenic response. Change in nutritional content contributes to the reorganization of developing maladaptations.