Gastrointestinal diseases and eating disorders are among the most common pathologies in the world. One of the most widespread and dangerous consequence of many eating disorders is an uncontrolled weight gain that often leads to obesity. This review focuses on the 15-year-long studies of obestatin, one of the potential regulators of eating behavior. This peptide contains 23 amino-acids and appears due to the processing of the preproghrelin gene responsible for the coding of another orexigenic protein ghrelin. Obestatin and ghrelin have multiple physiological functions, including appetite regulation. Obestatin was originally obtained from the gastric mucosa in rats, but subsequent studies showed that it could be expressed in various tissues and had different effects in various organs and tissues. This review emphasizes possible anorexigenic effects of this peptide and their mechanisms. Despite the 15 years of research on obestatin, its influence on different organs and the mechanism of anorexigenic effects in particular bring about a lot of discussion. This is primarily due to the ambiguity of the peptide receptors’ determination and is also related to the possible degradation of the molecule into small fragments, which, in turn, can have their own effects. The local effects of obestatin and its derivatives in peripheral tissues and the possible effect at the central level indicate the potential of these peptides for further studies. For example, these compounds can be considered as the potential therapeutic compounds for eating disorders’ treatment. The aim of this work was to describe the relevance of the problem associated with obesity treatment and to summarize the results of numerous studies on obestatin and its fragments and their effects on appetite regulation in order to explain its possible mechanisms.

Gastrointestinal diseases and eating disorders are among the most common pathologies in the world. One of the most widespread and dangerous consequence of many eating disorders is an uncontrolled weight gain that often leads to obesity. This review focuses on the 15-year-long studies of obestatin – one of the potential regulators of the eating behavior. This peptide contains 23 amino-acids and appears due to the processing of preproghrelin responsible for the coding of another orexigenic protein ghrelin. Obestatin and ghrelin have multiple physiological functions including the appetite regulation. Obestatin was originally obtained from the gastric mucosa in rats, but subsequent studies showed that it could be expressed in various tissues and had different effects in various organs and tissues. This review emphasizes possible anorexigenic effects of this peptide and their mechanisms. Despite the 15 years of research on obestatin, its influence on different organs and the mechanism of anorexigenic effects, in particular, bring about a lot of discussion. This is primarily due to the ambiguity of the peptide receptors determination, and is also related to the possible degradation of the molecule into the small fragments, which, in turn, can have their own effects. The local effects of obestatin and its derivatives in peripheral tissues and the possible effect at the central level indicate the potential of these peptides for the further studies. For example, these compounds can be considered as the potential therapeutic substances for eating disorders treatment. The aim of this work was to describe the relevance of the problem connected with obesity treatment and to summarize the results of numerous studies on obestatin and its fragments and their effects on the appetite regulation in order to explain its possible mechanisms.

The aim of the present study was to investigate the differences in the topological organization of functional brain networks between children with growth hormone deficiency (GHD) and those with idiopathic short stature (ISS).Thirty-one children with GHD and fifty-three children with ISS were recruited based on the results of GH stimulation tests. Resting-state fMRI data were acquired from all children. Whole brain functional connectivity density (FCD) analysis and subsequent seed-based functional connectivity analysis were used to explore the differences in functional brain networks between the children with ISS and GHD. Correlation analyses among the results of clinical laboratory examinations, neuropsychological scales and FCD values of different brain regions were applied.Compared with the ISS group, the GHD group exhibited significantly decreased FCDs in the left postcentral gyrus, right precentral gyrus and left cerebellar lobules 7b and 6. The subsequent functional connectivity analysis found decreased functional connectivity between lobules 7b and 6 of the left cerebellum as well as the left postcentral gyrus and right precentral gyrus in the GHD group compared to that in the ISS group. In addition, the FCD values of region 6 of the left cerebellum in the GHD group were negatively correlated with the scores on the Symptom Checklist-90 and Eysenck Personality Questionnaire. The FCD value of the left postcentral gyrus in children with ISS positively correlated with IGFBP-3 levels and was approximately correlated with IGF-1 levels.These findings highlight the impact of growth hormone deficiency on the brain network that mainly involves the somatosensory, somatic motor and cerebellum networks, which may contribute to the behavioural problems observed in these children.

to evaluate the influence of two maternal high-fat diets with different caloric contents on anxiety-like behavior in young-adult offspring and their sensitivity to acute fluoxetine.females Wistar rats were used and divided according to diet received during gestation and lactation: Control (CTR), high-fat/isocaloric (HI) and high-fat/high-caloric (HH). Offspring were subsequently divided into three subgroups according to acute administration of vehicle or fluoxetine (1 or 10 mg/kg). To assess animals’ anxiety-like behaviors, three tests were used: open field (OF), elevated plus-maze (EPM) and free-exploratory paradigm (FEP).In OF, HI and HH showed increased hyperactivity- and anxiety-related behaviors, HI being more hyperactive than HH. In response to fluoxetine, HI offspring decreased number of quadrants entered, decreased number of central entries and spent less time in rearing in peripheral areas, while HH offspring showed less time spent in rearing in the OF peripheral area. In EPM test, HI pups spent more time in closed arms than the HH pups. Fluoxetine decreased number of open arms entries for HI offspring and increased percentage of time spent in central area for HH animals. Maternal diet did not influence FEP test, neither HI nor HH presented a response after fluoxetine acute administration.Maternal high-fat diets influence offspring anxiety-like behavior in state-anxiety tests but not in trait-anxiety test. Responsiveness to acute fluoxetine depended on maternal diet, dose and which behavioral tests were being evaluated.

Pulmonary arteriovenous malformations (pAVMs) are major contributors to morbidity and mortality in hereditary hemorrhagic telangiectasia (HHT). Mutations in ENG and ACVRL1 underlie the vast majority of clinically diagnosed cases. The aims of this study were to characterize and compare the clinical and morphologic features of pAVMs between these two genotype groups.Sixty-six patients with HHT and affected family members were included. Genotype, phenotypic data, and imaging were obtained from medical records. Morphologic features of pAVMs were analyzed using computed tomography angiography. HHT symptoms, pAVM imaging characteristics, frequency of procedural intervention, and HHT severity scores were compared between ENG and ACVRL1 genotype groups.ENG mutation carriers were more likely than ACVRL1 mutation carriers to have pAVMs (P < 0.001) or multiple lesions (P = 0.03), and to undergo procedural intervention (P = 0.02). Additionally, pAVMs in ENG carriers were more likely to exhibit bilateral lung involvement and growth over time, although this did not reach statistical significance. The HHT severity score was significantly higher in ENG than in ACVRL1 (P = 0.02).The propensity and multiplicity of ENG-associated pAVMs may contribute to the higher disease severity in this genotype, as reflected by the HHT severity score and the frequency of interventional procedures.

The effects of chronic intranasal administration of 300 nmol/kg obestatin and its fragment FNAP-NH2 on behavioral activity and nociceptive threshold were examined in male Wistar rats with normal body weight or alimentary obesity. In normal rats, obestatin produced no effect on behavior and nociception, whereas FNAP-NH2 fragment enhanced risk-taking behavior. Rats with excess body weight demonstrated less pronounced risk-taking behavior and elevated nociceptive threshold in comparison with normal animals, but these differences were abolished by chronic administration of FNAP-NH2.

Single administration of the obestatin fragment 1-4 (300 nmol/kg) to male Wistar rats produced a significant weight loss in male rats on observation days 5-8, while in female rats only on day 8. In addition, males demonstrated decreased risk factor in the elevated plus-maze test, but no effect of the preparation on behavior of female rats was revealed. Obestatin fragment 1-4 had no effect on corticosterone level 1 week after single administration in both females and male rats.

Catalpol, a major compound in Rehmannia glutinosa with both medicinal and nutritional values, has been previously confirmed to shorten the duration of immobility in mice exposed to tail suspension and forced swimming tests. This study attempted to examine the anti-depressive mechanisms of catalpol in rats undergoing chronic unpredictable mild stress (CUMS) by involving brain-derived neurotrophic factor (BDNF) and cyclooxygenase-2 (COX-2). CUMS-exposed rats were given catalpol daily (5, 10, and 20 mg/kg, ig) or a reference drug, fluoxetine hydrochloride (FH, 10 mg/kg, ig), at 5 weeks after starting the CUMS procedure. Sucrose preference test was performed to observe depression-like behavior, and serum and brain tissues were used for neurochemical and fluorescent quantitative reverse transcription PCR analysis. CUMS induced depression-like behavior, whereas catalpol and FH administration attenuated this symptom. Moreover, CUMS caused excessively elevated levels of serum corticosterone, an index of hypothalamic–pituitary–adrenal (HPA) axis hyperactivation, in a manner attenuated by catalpol and FH administration. Catalpol administration also further decreased BDNF activities, downregulated the mRNA expression of BDNF and tropomyosin-related kinase B (TrkB), and reversed the excessive elevation in the activities and mRNA expression levels of COX-2 and prostaglandin E2 (PGE2) in the hippocampus and frontal cortex of rats undergoing CUMS. Results indicate that catalpol can ameliorate CUMS-induced depression-like behavior, and suggest its mechanisms may partially be ascribed to restoring HPA axis dysfunctions, upregulating BDNF expression and its cognate receptor TrkB, and downregulating COX-2 expression, thereby reducing PGE2 levels in the brain.

We studied the effects of anorectic peptide obestatin and its fragment (1-4) on the antioxidant defense system in animals with normal and experimentally induced increased body weight. In rats with normal body weight, no changes in activity of the antioxidant defense system 1 week after single administration of the substances. After chronic administration of obestatin and fragment (1-4) for 1 week, total antioxidant capacity of the plasma decreased; obestatin also lowered the content of TBA-reactive products. In the overweight rats, SOD-like activity in the plasma increased 1 week after chronic administration of obestatin. Hence, obestatin and its fragment (1-4) induced changes in the antioxidant defense system only after chronic administration.