314 research outputs found
Oleoylethanolamide in the homeostatic and non-homeostatic control of eating
No full textThe goal of the present study is to evaluate the role of OEA as a potential novel pharmacological target for the treatment of obesity and eating disorders, two major health problems worldwide.
OEA’s ability in inducing consistent and sustained food intake suppression in rats and mice, that is mediated by PPAR-α activation, has been well characterized over the last two decades from my laboratory and from other research groups. In fact, it is now well recognized that the pro-satiety effect of OEA is strictly dependent on the involvement of key brain hypothalamic and hindbrain areas.
However, a crucial aspect remained to be fully elucidated, such as the way by which systemically administered OEA can reach the CNS from the periphery and whether it is able to permeate the brain parenchyma.
In this background, circumventricular organs, such as the AP in the brainstem, are attracting a great deal of attention for their possible role in allowing the direct access to the brain for circulating peptides and other peripheral signals. Moreover, previous data showed that the i.p. administration of OEA, strongly activates neurons of the AP and significantly stimulates c-fos transcription in the subpostremal part of the NST, which is the closest sub nucleus to the AP.
Based on these premises, in order to better delineate the mechanism underlying the eating-inhibitory effects of OEA, the aim of chapter II was to investigate the involvement of the AP in mediating OEA hypophagic action.
To this purpose, in collaboration with Prof. Thomas Lutz at University of Zurich, we subjected rats to a surgical ablation of the AP and evaluated the effects of i.p. OEA administration (10 mg kg−1) on food intake, on Fos expression, on OXY immunoreactivity at both PVN and neurohypophysial level and on the expression of DBH within the brainstem and PVN. Further, we aimed to assess the phenotype of neuronal populations activated by OEA in the brainstem of controls and lesioned rats; to this aim, we assessed, also, whether OEA induced Fos expression co-localized with DBH as marker for noradrenergic neurons. Finally, as last step of our study, we investigated PPAR-alpha expression within the AP.
Furthermore, since there are no observations demonstrating the ability of OEA to permeate the brain parenchyma, in the chapter III I aimed to investigate whether systemically administered OEA might directly reach and permeate the CNS through circumventricular organs devoid of a functional BBB, such as the AP and the ME.
To this purpose, in collaboration with Prof. Lutz and Prof Giulio Muccioli at Université Catholique de Louvain, male Wistar rats were sacrificed at different time points (2.5, 5, 15, 30, 60 minutes) after acute administration of OEA (10 mg kg-1, i.p.). Plasma and different brain areas were collected for UPLC-MS/MS quantification of the main NAEs (including OEA, AEA, PEA, SEA, and LEA), and 2-arachidonoyl-glycerol (2-AG). In particular, in order to selectively investigate OEA concentrations within a variety of PPAR-α-expressing cerebral regions, selected brain areas of interest (AP, ME, NST, ventral and dorsal hippocampus (vHipp and dHipp)) were microdissected and used in this study.
Finally, since current knowledge supports a relationship between neurobiological as well as psychological aspects of overeating, in chapter IV I also investigated the OEA’s pro-satiety action in a rat model of BED, which is a prototypical eating-related maladaptive behaviour that may determine fluctuations in body weight and in some instance may cause obesity.
Among the different networks involved in the behavioural effect of OEA, it has been demonstrated that the systemic administration of OEA to obese rodents restores a “normal brain dopaminergic activity”, which resulted dampened by the excess of fat intake. Moreover, evidence suggests that OEA attenuates the effect of stress by dampening the hyperactivity of the HPA axis. Since both the abnormal dopaminergic transmission and the hyperactivation of HPA axis are considered mechanisms underlying the pathophysiology of BED, by acting at both the two deregulated conditions OEA might represent a potential novel pharmacological target for controlling aberrant eating patterns occurring in BED.
Based on these premises, in order to test this hypothesis in collaboration with Prof. Carlo Cifani of University of Camerino we evaluated OEA effects in a BED model in which female rats with a history of intermittent food restriction show binge-like palatable food consumption after a 15-minute exposure to the sight of the palatable food (frustration stress).
In this model, we investigated the anti-bingeing acute effects of OEA (2.5, 5 or 10 mg kg-1, i.p.) on HPF intake and analysed the neurobiological bases of these effects by focusing on the brain pattern of c-Fos expression, on DA release in the shell of the nucleus accumbens (AcbSh), on monoamine concentrations/turnovers in selected brain regions and on both CRF and OXY mRNA in hypothalamic and extra hypothalamic areas
Influence of the ovarian cycle and estradiol in frustration stress-induced binge-like palatable food consumption in female rats with a history of food restriction
No full textEating disorders show marked gender differences [1] and several epidemiologic
studies suggest that binge eating episodes are more common in females than in males [2]. To
further investigate the mechanisms underlying this sex difference, we used an animal model first described by Cifani et al. [3], in which binge eating is evoked in female rats by food restriction
followed by frustration stress (15 min exposure to the sight of the palatable food). We aimed to
determine whether binge eating behavior varies across the estrus cycle and is influenced by
estradiol in ovariectomized (OVX) rats. Finally, using immunocytochemistry, we quantified the
activation of extracellular signal regulated kinase (ERK) signaling pathway in OVX rats treated
with estradiol or oil vehicle, in basolateral (BLA) and the central (CeA) nuclei of the amygdala,
paraventricular nucleus of hypothalamus (PVN) and arcuate nucleus (ARC). Restricted and
stressed non-estrus rats showed binge eating behavior in comparison to the control not restricted
and not stressed rats. This response was not present in restricted and stressed rats in estrus, and in
OVX rats treated with estradiol. This lack of binge eating behavior was accompanied by a
significant decrease in ERK phosphorylation in ARC, PVN and in the CeA, but not in BLA, in
comparison to non-estrous rats and to not restricted and not stressed animals. Our behavioral
findings show that binge eating does not occur during the estrous phase. Because this was
recapitulated in OVX rats treated with estradiol, we propose that the inhibitory effect of estradiol
on eating is partly responsible for the lack of bingeing. These findings are consistent with reports
in women with bulimia nervosa [4], in whom the binge frequency decreased during the follicular
phase, a time of the menstrual cycle when eating is also lowest. These results extend our
previous findings and increase the validity of our model, such that it can be used in translational
studies of the mechanism of binge eating behavior. References: [1] Klump et al. 2008 Psych Med
38:1749-57 [2] Cifani et al. 2009 Psychopharmology 204:113-125 [3] Hudson et al. 2007 Biol
Psychiatry 61:348-358 [4] Edler et al. 2007 Psych Med 37:131-14
CRF1 receptor antagonists as novel pharmacological treatment for bingeing-related eating disorders
No full textThe interaction between dieting and stress is a key factor for triggering binge episodes on palatable food in human binge eaters. Corticotropin releasing factor (CRF) mechanisms are known to play a pivotal role in the regulation of this maladaptive behavior.
The present study evaluated the effect of the CRF1 receptor antagonist R121919 and the corticosterone synthesis inhibitor metyrapone in female rats in which binge eating was evoked by stress and cycles of food restrictions.
Rats were first subjected or not to repeated cycles of regular chow food restriction/refeeding during which they were also given limited access (2 h) to palatable food. On the test day, rats were either exposed or not to the sight of the palatable food for 15 minutes without allowing access (frustration stress), before assessing food consumption for 2 h.
Systemic injections of the CRF1 receptor antagonist R121919, but not of the metyrapone, blocked binge-like eating behavior. Moreover, corticosterone injection did not induce binge eating in non-stressed rats.
Restricted and stressed rats showed up-regulation of crh1 receptor mRNA signal in the bed nucleus of the stria terminalis (BNST) and central amygdala (CeA) but not in basolateral amygdala (BLA) or in the paraventricular nucleus. Injection of CRF receptor antagonist D-Phe-CRF(12– 41) in CeA but not in the BLA blocked binge-like eating behavior.
These findings demonstrate that extra-hypothalamic CRF1 receptors, rather than those involved in endocrine functions, are involved in binge eating. CRF1 receptor antagonism may represent a novel pharmacological treatment for binge-related eating disorders
Satricum
No full textSistematica sintesi bibliografica e di storia critica degli studi relativa alla città latina e volsca di Satricu
Olfactory receptor 984 a new target for obesity in rats and humans?
No full textThe genetic architecture of obesity and brain disorders are multifactorial and linked to each other. Feeding behavior and body weight are controlled through complex interactions between the central nervous system and peripheral organs. We have previously investigated the individual sensitivity to weight gain/resistance in rats developing obesity (diet-induced obesity, DIO) or not (diet resistant, DR), when fed with a high fat diet (Cifani et al., 2015). Both groups were extensively characterized and we used expression analysis in visceral adipose tissue (AT) by RNA-Chip technology to identify potential underlying target genes. One candidate gene, olfactory receptor genes OLR984, was identified in AT of rats and we investigated this gene in human paired samples of visceral and subcutaneous (SC) AT (n = 224) of individuals with a wide range of body weight and glucose homeostasis.
Gene expression analysis in AT of DR and DIO group identified OLR984 as candidate target genes in visceral AT. In humans, OLR984 genes were differentially expressed between SC and visceral AT and its mRNA was strongly correlated with parameters of obesity and glucose metabolism.
Our data provide a novel candidate gene for obesity strongly associated with body mass regulation in rats. Our human mRNA results suggest that changes in AT OLR984 expression are related to obesity parameters and glucose homeostasis.
1 Cifani et al. (2015). Frontiers in neuroscience 9:187
Influence of the ovarian cycle and estradiol on binge eating evoked in female rats by food restriction followed by frustration stress.
No full textEating disorders show marked gender differences (Klump et al 2008 Psych Med 38:1749-57) and several epidemiologic studies suggest that binge eating episodes are more common in females than in males. To further investigate the mechanisms underlying this sex difference, we used an animal model first described by Cifani et al (2009 Psychopharm 204:113-125), in which binge-eating is evoked in female rats by 3 cycles of food restriction followed by frustration stress (15 min exposure to the sight of the palatable food). We aimed to determine whether binge eating behavior (1) varies across the estrus cycle and (2) is influenced by estradiol (E2) in ovariectomized (OVX) rats. Finally, using immunocytochemistry, we quantified the activation of extracellular signal regulated kinase (ERK) signaling pathway in OVX rats treated with E2 or oil, in basolateral (BLA) and the central (CeA) amygdala, paraventricular nucleus of hypothalamus (PVN) and arcuate nucleus (ARC).
Restricted and stressed rats in estrus and OVX rats treated with E2 did not show binge eating behavior in comparison to the control non-restricted and non-stressed rats. The lack of binge eating behavior in estrous rats was accompanied by a significant decrease in ERK phosphorylation in ARC, PVN and in the CeA, but not in BLA, in comparison to non-estrous rats and to non-restricted and non-stressed animals.
Our findings show that binge eating does not occur during the estrous phase. Because this was recapitulated in OVX rats treated with E2, they suggest that the inhibitory effect of E2 on eating is partly responsible for the lack of bingeing. These results are consistent with reports in women with bulimia nervosa (Edler et al 2007 Psych Med, 37:131-141) and extend our previous findings and increase the validity of our model, that can be used in translational studies of the mechanism of binge eating behavior
Oleoylethanolamide in the gut-brain axis
No full textOleoylethanolamide (OEA), a PPAR-α agonist, is a mediator of satiety. After peripheral administration, OEA induces Fos expression and activation in areas of the CNS involved in the control of feeding behavior and energy homeostasis, such as the nucleus of the solitary tract (NST) and in the area postrema (AP) in the brainstem, the hypothalamic paraventricular (PVN), supraoptic (SON) and ventral tuberomammillary (vTMN) nuclei. Moreover, it is known to increase the noradrenergic trasmission in the NST and AP, by increasing the expression of the dopamine-β-hydroxylase (DBH). Visceral ascending fibers were hypothesized to mediate such effects, but recent findings demonstrate that abdominal vagal afferents are not necessary for the anorectic effect of OEA. In fact, OEA is able to decrease food intake both in rats that underwent a subdiaphragmatic vagal deafferentation (SDA), a surgical procedure that eliminates all abdominal vagal afferents but spares about 50% of the vagal efferents, and in SHAM controls. Thus, the aim of the present work was to better elucidate the role of abdominal vagal afferents in mediating OEA's effects on the CNS. To meet this aim, we subjected rats to SDA surgery, using SHAM rats as control. By using immunohistochemistry, Fos and DBH expression patterns were investigated in the NST, in the AP, and in the hypothalamus after OEA administration (10 mg kg -1).
Consistently with the behavioral results, OEA increases Fos expression in the NST and in the AP. Moreover, in these nuclei, SDA did not cause any alteration of DBH expression. In the hypothalamus, in line with the behavioral results, OEA is able to increase Fos expression in the PVN and the vTMN, even though in the latter does not reach statistical significance.
Overall, our findings indicate that vagal afferents are not strictly necessary for the satiety effect of OEA at both behavioral and neurochemical levels
CRF system involvement in compulsive eating: new cues from pre-clinical rat and C. elegans models
No full textAims: Stress, together with dieting and environmental negative affects is a common trigger of eating disorders, especially binge eating (BE) disorder. The aim of this study was to investigate the regulation of the CRF/CRF-1R-system in a validated rat model of BE and to develop an innovative BE-model in C. elegans, as well as to observe the potential involvement seb-3 gene, similar to the mammalian CRF-1R, on BE behavior.
Methods: Female rats were exposed to food restriction and stress. mRNA abundances and DNA methylation were quantified by qRT-PCR and pyrosequencing. N2 worms and two different seb-3 mutants were exposure to starvation and acute stress, then alterations in feeding activity were recorded.
Results: CRF system is up regulated in the VTA of rats restricted and exposed to stress, and these changes appear to be due to a reduction in DNA methylation at gene promoters. The pharyngeal pumping rate was increased in N2 worms exposed to starvation and stress conditions when compared to animals just starved. Moreover, seb-3 gain-of-function-worms resulted to be more sensitive to the starvation and stress conditions wherever, seb-3 loss-of-function-worms seemed to be not responding.
Conclusions: These data further support the role of CRF-system in compulsive-feeding behavior. Morever, our new proposed BE-model in C. elegans could improve the understanding of the role played by CRF as well as other brain circuits and by environmental triggers in affecting food intake. We believe that this model would give the opportunity to monitor genetic modifications in order to follow disease development easily across worms life-span
Evaluation of antimicrobial activity of probiotic bacteria against salmonella enterica subsp. enterica serovar typhimurium 1344 in a common medium under different environmental conditions.
No full textChronic intracerebroventricular infusion of nociceptin/orphanin FQ increases food and ethanol intake in alcohol-preferring rats
No full textCentral administration of low doses of nociceptin/orphanin FQ (N/OFQ), the endogenous
ligand of the opioid-like orphan receptor NOP, have been shown to reduce ethanol consumption,
ethanol-induced conditioned place preference and stress-induced reinstatement
of alcohol-seeking behavior in alcohol preferring rats. The present study evaluated the effect
of continuous (7 days) lateral brain ventricle infusions of N/OFQ (0, 0.25, 1, 4, and 8 mg/h), by
means of osmotic mini-pumps, on 10% ethanol intake in Marchigian-Sardinian alcoholpreferring
(msP) rats provided 2 h or 24 h access to it. N/OFQ dose-dependently increased
food intake in msP rats. On the other hand, in contrast to previous studies with acute
injections, continuous lateral brain ventricle infusion of high doses of N/OFQ increased
ethanol consumption when the ethanol solution was available for 24 h/day or 2 h/day. The
present study demonstrates that continuous activation of the opioidergic N/OFQ receptor
does not blunt the reinforcing effects of ethanol. Moreover, the data suggest that continuous
activation of the opioidergic N/OFQ receptor is not a suitable way to reduce alcohol abuse
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