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FTO genotype impacts food intake and corticolimbic activation.

BACKGROUND: Variants in the first intron of the fat mass and obesity-associated (FTO) gene increase obesity risk. People with "high-risk" FTO genotypes exhibit preference for high-fat foods, reduced satiety responsiveness, and greater food intake consistent with impaired satiety. OBJECTIVE: We sought central nervous system mechanisms that might underlie impaired satiety perception in people with a higher risk of obesity based on their FTO genotype. DESIGN: We performed a cross-sectional study in a sample that was enriched for obesity and included 20 higher-risk participants with the AA (risk

Postnatal prebiotic fibre intake mitigates some detrimental metabolic outcomes of early overnutrition in rats.

PURPOSE: Overnutrition during early development has been linked to metabolic disease and obesity in adulthood. Interventions to ameliorate this metabolic malprogramming are needed. Our objective was to determine whether prebiotic fibre would reduce weight gain and improve satiety hormone profiles in rats overnourished during the suckling period. METHODS: Male Sprague-Dawley rats reared in small litter (SL 3 pups) or normal litter (NL 12 pups) were randomized at weaning to AIN-93 (control) or a 10 % oligofructose (OFS) diet for 16 weeks. Body composition, an oral glucose tolerance test for glu

Current concepts in bone and reproductive health in adolescents with anorexia nervosa.

Anorexia nervosa (AN) initiates an adaptive response at the level of the hypothalamus, which results in a complex interplay involving most elements of the neuroendocrine axis. Consequences of onset of disease in adolescence include amenorrhoea, pubertal arrest with potential loss of target height, and osteoporosis with reduced capacity for future attainment of peak bone mass. With recovery, delay in restoration of menses is common. Hormonal therapies for restoration of bone mineral density (BMD) in adolescents have shown limited efficacy. This review will discuss the reproductive endocrine eff

Hesperidin facilitating gastrointestinal motility by "Gut-brain axis" and "SCF/C-Kit signaling pathways".

Hesperidin shows promising results as a potential feed additive for enhancing gastrointestinal motility in animals. Gastrointestinal functio … n group. Incorporation of hesperidin into the broilers' diet significantly enhances serum levels of ghrelin, encompassing serotonin (5-HT), motilin (MTL), cholecystokinin (CCK), and Stem Cell Factor (SCF) as well as substance P (SP) in the gizzard and duodenal tissues while reducing vasoactive intestinal peptide (VIP) levels (P < 0.05). The group administ …

Type 2 Diabetes and the Multifaceted Gut-X Axes.

Type 2 diabetes (T2D) is a complex metabolic disease characterized by chronic hyperglycemia due to insulin resistance and inadequate insulin … lucagon secretion and β-cell health; (2) Gut-Endocrine Axis: enteroendocrine signals (e.g., PYY and ghrelin) and neural pathways that link the gut with appetite regulation, adipose tissue, and systemic metabolism; (3) Gut-Liver Axis: the role of microbiota-modified bile acids (FXR/TGR5 pathways) and bacterial endotoxins in non-alcoholic fatty liver diseas …

Which is the ideal target for preterm growth?

In the last two decades the improved survival of very low birth weight (VLBW) and extremely low birth weight (ELBW) infants has underscored the problem of postnatal growth failure of these subjects. Notwithstanding the evident improvements in the general management of these infants during the hospital stay, most of them acquire a significant extrauterine growth restriction (EUGR). Frequent illnesses, medical and surgical therapies, feeding intolerance and, most of all, inadequacy of nutrient deliveries are responsible for the great part of this growth failure. However other factors, such as ge

Discovery and pharmacological evaluation of growth hormone secretagogue receptor antagonists.

The discovery and pharmacological evaluation of potent, selective, and orally bioavailable growth hormone secretagogue receptor (GHS-R) antagonists are reported. Previously, 2,4-diaminopyrimidine-based GHS-R antagonists reported from our laboratories have been shown to be dihydrofolate reductase (DHFR) inhibitors. By comparing the X-ray crystal structure of DHFR docked with our GHS-R antagonists and GHS-R modeling, we designed and synthesized a series of potent and DHFR selective GHS-R antagonists with good pharmacokinetic (PK) profiles. An amide derivative 13d (Ca2+ flux IC50 = 188 nM, [brain

[Association of obesity and depression].

It has been long known that the frequency of overweight and obese people is higher among depressed and bipolar patients than in the general population. The marked alteration of body weight (and appetite) is one of the most frequent of the 9 symptoms of major depressive episode, and these symptoms occur during recurrent episodes of depression with a remarkably high consequence. According to studies with representative adult population samples, in case of obesity (BMI over 30) unipolar or bipolar depression is significantly more frequently (20-45%) observable. Since in case of depressed patients

New genetic findings in a large cohort of congenital hypogonadotropic hypogonadism.

CONTEXT: Congenital hypogonadotropic hypogonadism (CHH) is a rare condition caused by GnRH deficiency. Several genes have been associated with the pathogenesis of CHH, but most cases still remain without a molecular diagnosis. The advent of next-generation sequencing (NGS) has allowed the simultaneous genotyping of several regions, faster, making possible the extension of the genetic knowledge of CHH. OBJECTIVE: Genetic characterization of a large cohort of Brazilian CHH patients. DESIGN AND PATIENTS: A cohort of 130 unrelated patients (91 males, 39 females) with CHH (75 normosmic CHH, 55 Ka

Effect of two bakery products on short-term food intake and gut-hormones in young adults: a pilot study.

The aim of this study is to compare the effect of conventional bread and a whole grain bread on appetite and energy intake, satiety and satiety gut-hormones. A randomized controlled crossover pilot study was carried out in 11 university students (age: 18.7 ± 0.9 years; body mass index: 22.7 ± 2.7 kg/m(2)). Participants consumed two different mid-morning cereal-based snacks, including a conventional or whole grain bread. Two testing days were completed, including satiety questionnaires, blood sampling and consumption of standardized breakfast, mid-morning test-snacks and ad libitum lunch. Sever

Satiety hormone and metabolomic response to an intermittent high energy diet differs in rats consuming long-term diets high in protein or prebiotic fiber.

Large differences in the composition of diet between early development and adulthood can have detrimental effects on obesity risk. We examined the effects of an intermittent high fat/sucrose diet (HFS) on satiety hormone and serum metabolite response in disparate diets. Wistar rat pups were fed control (C), high prebiotic fiber (HF) or high protein (HP) diets (weaning to 16 weeks), HFS diet challenged (6 weeks), and finally reverted to their respective C, HF, or HP diet (4 weeks). At conclusion, measurement of body composition and satiety hormones was accompanied by (1)H NMR metabolic profiles

Towards frailty biomarkers: Candidates from genes and pathways regulated in aging and age-related diseases.

OBJECTIVE: Use of the frailty index to measure an accumulation of deficits has been proven a valuable method for identifying elderly people … 1), agrin (AGRN), (6) IGF-1 (insulin-like growth factor 1), resistin (RETN), adiponectin (ADIPOQ), ghrelin (GHRL), growth hormone (GH), (7) microparticle panel (to be further defined), GpnmB (glycoprotein nonmetastatic melanoma protein B) and lactoferrin (LTF). We believe that these predicted panels need to be experimentally explored in animal models and …

Molecular therapeutic strategies targeting pancreatic cancer induced cachexia.

Pancreatic cancer (PC) induced cachexia is a complex metabolic syndrome associated with significantly increased morbidity and mortality and reduced quality of life. The pathophysiology of cachexia is complex and poorly understood. Many molecular signaling pathways are involved in PC and cachexia. Though our understanding of cancer cachexia is growing, therapeutic options remain limited. Thus, further discovery and investigation of the molecular signaling pathways involved in the pathophysiology of cachexia can be applied to development of targeted therapies. This review focuses on three main p

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… Ghrelin Ghrelin is a peptide hormone secreted by the stomach and pancreas and modulates energy homeostasis, increases appetite, and stimulates growth hormone (GH) secretion[ 76 ]. … Furthermore, no clinical trials to date have been conducted to evaluate effectiveness of ghrelin or ghrelin agonists in PC associated cachexia. …

Another Weapon against Cancer and Metastasis: Physical-Activity-Dependent Effects on Adiposity and Adipokines.

Physically active behavior has been associated with a reduced risk of developing certain types of cancer and improved psychological conditions for patients by reducing anxiety and depression, in turn improving the quality of life of cancer patients. On the other hand, the correlations between inactivity, sedentary behavior, and overweight and obesity with the risk of development and progression of various cancers are well studied, mainly in middle-aged and elderly subjects. In this article, we have revised the evidence on the effects of physical activity on the expression and release of the ad

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… Ghrelin—Physiological Functions and Regulation. Eur. Endocrinol. 2015;11:90–95. doi: 10.17925/EE.2015.11.02.90. 98. Lien G.S., Lin C.H., Yang Y.L., Wu M.S., Chen B.C. Ghrelin induces colon cancer cell proliferation through the GHS-R, Ras, PI3K, Akt, and mTOR signaling pathways. Eur. J. … A novel human ghrelin variant (In1-ghrelin) and ghrelin-O-acyltransferase are overexpressed in breast cancer: Potential pathophysiological relevance. PLoS ONE. 2011;6:e23302. doi: 10.1371/journal.pone.0023302. 105. Xu X., Jhun B.S., Ha C.H., Jin Z.G. …

Помимо потери веса: изучение неврологических последствий изменённой микробиоты кишечника послекариатрической хирургии.

В настоящем обзоре обсуждаются результаты, связанные с неврологическими расстройствами, кишечной микробиотой и бариатрической хирургией, с уделением особого внимания нейротрансмиттерам, нейроэндокрину, патофизиологии бактерий, способствующих возникновению нарушений, и возможным терапевтическим вмешательствам. Исследования в области нейротрансмиттеров показывают, что их уровни сильно зависят от кишечного микробиота, которая может связать их с такими неврологическими расстройствами, как болезнь Альцгеймера, болезнь Паркинсона, множественный склероз, депрессия и расстройства спектра аутизма. Пато

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… Together, these findings suggest that both inflammatory cytokines and SCFAs play an active role in regulating ghrelin release. Interestingly, ghrelin has been shown to have neuroprotective effects. … Individuals suffering from Parkinson’s disease (PD) and AD exhibit disrupted ghrelin release [ 58 , 59 ]. Moreover, ghrelin plays a role in memory, mood, and other brain functions [ 58 , 59 ]. …

Nutrient status modulates the expression of nesfatin-1 encoding nucleobindin 2A and 2B mRNAs in zebrafish gut, liver and brain.

Nesfatin-1 is a naturally occurring, 82-amino acid peptide processed from the precursor nucleobindin 2 (NUCB2), a highly conserved protein among vertebrates. In fish, two isoforms of NUCB2 (NUCB2A and NUCB2B) exist, and nesfatin-1 has been identified in goldfish and Ya fish. We recently reported the presence and appetite suppressing effects of nesfatin-1 in goldfish. The main objectives of this study were to characterize NUCB2 in zebrafish, and determine whether NUCB2 mRNAs are affected by food availability. Tissue distribution of NUCB2A and NUCB2B mRNAs, and NUCB2/nesfatin-1-like immunoreacti

Obestatin Plays Beneficial Role in Cardiomyocyte Injury Induced by Ischemia-Reperfusion In Vivo and In Vitro.

BACKGROUND Obestatin, primarily recognized as a peptide within the gastrointestinal system, has been shown to benefit the cardiovascular system. We designed this experiment to study the protective role and underlying mechanism of obestatin against ischemia-reperfusion(I/R) injury in myocardial cells. MATERIAL AND METHODS In an In vivo experiment, LAD was ligated for 0.5 h and then opened for reperfusion with obestatin for 24 h. Then, the infarction area was shown with TTC staining, and inflammation factors in serum were analyzed by qRT-PCR. In primary cultured cardiomyocytes, we measured the l

Историческое развитие иммуноэндокринных концепций психических расстройств и их терапии.

Отношения между центральной нервной, иммунной и эндокринной системами являются предметом психиатрических исследований, особенно в области депрессии и шизофрения. У поля длинные предтечи. Наблюдаемые явления, связанные с этими отношениями, восходят к неолитической эпохе. Теории иммуноэндокринной системы в самом широком смысле записаны в древности. В 19th Крепелин и Вагнер-Джаурег сообщили о первых клинических наблюдениях у пациентов психиатрических учреждений. Von Bestow, Эддисон и Кушинг описали психические симптомы у пациентов, страдающих эндокринными заболеваниями. :: 20th откровение века с

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… Increased ghrelin levels also seem to be characteristic for alcoholics during detoxification [ 120 ]. … Finally, tests on mice have shown that the intraventricular application of ghrelin led to more alcohol being consumed, whereas the application of a ghrelin antagonist reduced the longing for alcohol [ 121 ]. 4.3. …

Gender-dependent consequences of chronic olanzapine in the rat: effects on body weight, inflammatory, metabolic and microbiota parameters.

RATIONALE: Atypical antipsychotic drugs (AAPDs) such as olanzapine have a serious side effect profile including weight gain and metabolic dysfunction, and a number of studies have suggested a role for gender in the susceptibility to these effects. In recent times, the gut microbiota has been recognised as a major contributor to the regulation of body weight and metabolism. Thus, we investigated the effects of olanzapine on body weight, behaviour, gut microbiota and inflammatory and metabolic markers in both male and female rats. METHODS: Male and female rats received olanzapine (2 or 4 mg/kg/

Abstracts of the 3rd International Conference on Cancer Cachexia, September 23–25, 2016 in Washington, DC, USA

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… Mechanisms of action of ghrelin in cancer cachexia Jose M. … However, recent data suggest that some of ghrelin's effects in these tissues are GRLN independent. …