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1.
Current Aspects of the Role of Autoantibodies Directed Against Appetite-Regulating Hormones and the Gut Microbiome in Eating Disorders.
Smitka, K, Prochazkova, P, Roubalova, R, Dvorak, J, Papezova, H, Hill, M, Pokorny, J, Kittnar, O, Bilej, M, Tlaskalova-Hogenova, H
Frontiers in endocrinology. 2021;:613983
Abstract
The equilibrium and reciprocal actions among appetite-stimulating (orexigenic) and appetite-suppressing (anorexigenic) signals synthesized in the gut, brain, microbiome and adipose tissue (AT), seems to play a pivotal role in the regulation of food intake and feeding behavior, anxiety, and depression. A dysregulation of mechanisms controlling the energy balance may result in eating disorders such as anorexia nervosa (AN) and bulimia nervosa (BN). AN is a psychiatric disease defined by chronic self-induced extreme dietary restriction leading to an extremely low body weight and adiposity. BN is defined as out-of-control binge eating, which is compensated by self-induced vomiting, fasting, or excessive exercise. Certain gut microbiota-related compounds, like bacterial chaperone protein Escherichia coli caseinolytic protease B (ClpB) and food-derived antigens were recently described to trigger the production of autoantibodies cross-reacting with appetite-regulating hormones and neurotransmitters. Gut microbiome may be a potential manipulator for AT and energy homeostasis. Thus, the regulation of appetite, emotion, mood, and nutritional status is also under the control of neuroimmunoendocrine mechanisms by secretion of autoantibodies directed against neuropeptides, neuroactive metabolites, and peptides. In AN and BN, altered cholinergic, dopaminergic, adrenergic, and serotonergic relays may lead to abnormal AT, gut, and brain hormone secretion. The present review summarizes updated knowledge regarding the gut dysbiosis, gut-barrier permeability, short-chain fatty acids (SCFA), fecal microbial transplantation (FMT), blood-brain barrier permeability, and autoantibodies within the ghrelin and melanocortin systems in eating disorders. We expect that the new knowledge may be used for the development of a novel preventive and therapeutic approach for treatment of AN and BN.
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2.
Involvement of Ghrelin Dynamics in Stress-Induced Eating Disorder: Effects of Sex and Aging.
Yamada, C
International journal of molecular sciences. 2021;(21)
Abstract
Stress, a factor that affects appetite in our daily lives, enhances or suppresses appetite and changes palatability. However, so far, the mechanisms underlying the link between stress and eating have not been fully elucidated. Among the peripherally produced appetite-related peptides, ghrelin is the only orexigenic peptide, and abnormalities in the dynamics and reactivity of this peptide are involved in appetite abnormalities in various diseases and psychological states. This review presents an overview of the research results of studies evaluating the effects of various stresses on appetite. The first half of this review describes the relationship between appetite and stress, and the second half describes the relationship between the appetite-promoting peptide ghrelin and stress. The effects of sex differences and aging under stress on appetite are also described.
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3.
Endocrinopathies and cancer cachexia.
Dev, R, Del Fabbro, E, Dalal, S
Current opinion in supportive and palliative care. 2019;(4):286-291
Abstract
PURPOSE OF REVIEW Cancer cachexia cannot be easily reversed by standard nutritional support and interventions directed at underlying metabolic derangements may be needed to prevent or reverse cachexia and maintain healthy body composition. The following review will highlight the contribution and potential therapeutic interventions for insulin resistance, alterations in ghrelin signaling, and hypogonadism in cancer patients. RECENT FINDINGS In addition to decreased caloric intake, chronic inflammation, and altered metabolism of glucose, proteins and lipids, endocrine abnormalities can propagate weight loss or changes in body composition in cancer patients. SUMMARY Cancer cachexia, loss of muscle mass with or without the loss of fat mass, is a multifactorial syndrome, which is associated with increased morbidity and mortality. Currently, limited therapeutic options for the treatment of weight loss in cancer patients exist, which lead to clinically meaningful improvements in weight gain and performance status. Treatment directed at underlying insulin resistance, low testosterone, and altered ghrelin sensitivity, in the future, may lead to potential therapeutic options for loss of lean body mass and cancer cachexia.
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4.
Efficacy of Anamorelin, a Novel Non-Peptide Ghrelin Analogue, in Patients with Advanced Non-Small Cell Lung Cancer (NSCLC) and Cachexia-Review and Expert Opinion.
Currow, DC, Maddocks, M, Cella, D, Muscaritoli, M
International journal of molecular sciences. 2018;(11)
Abstract
Cancer cachexia is a multilayered syndrome consisting of the interaction between tumor cells and the host, at times modulated by the pharmacologic treatments used for tumor control. Key cellular and soluble mediators, activated because of this interaction, induce metabolic and nutritional alterations. This results in mass and functional changes systemically, and can lead to increased morbidity and reduced length and quality of life. For most solid malignancies, a cure remains an unrealistic goal, and targeting the key mediators is ineffective because of their heterogeneity/redundancy. The most beneficial approach is to target underlying systemic mechanisms, an approach where the novel non-peptide ghrelin analogue anamorelin has the advantage of stimulating appetite and possibly food intake, as well as promoting anabolism and significant muscle mass gain. In the ROMANA studies, compared with placebo, anamorelin significantly increased lean body mass in non-small cell lung cancer (NSCLC) patients. Body composition analysis suggested that anamorelin is an active anabolic agent in patients with NSCLC, without the side effects of other anabolic drugs. Anamorelin also induced a significant and meaningful improvement of anorexia/cachexia symptoms. The ROMANA trials have provided unprecedented knowledge, highlighting the therapeutic effects of anamorelin as an initial, but significant, step toward directly managing cancer cachexia.
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5.
Appetite hormones in children and adolescents with cancer: a systematic review of observational studies.
Fayh, APT, Bezerra, ADL, Friedman, R
Nutricion hospitalaria. 2018;(1):201-210
Abstract
INTRODUCTION Malnutrition in children with cancer is a significant risk factor for negative outcomes, but in the clinical practice setting, it is difficult to pinpoint which factors operate to cause substantial weight loss and malnutrition in a given patient. Appetite-related hormones like ghrelin and leptin are among possible mediators. However, only few studies have examined the role of these hormones in pediatric patients with cancer to date. Thus, the purpose of this study was to systematically review possible changes in the levels of appetite hormones, specially leptin and ghrelin, in pediatric patients with cancer. MATERIAL AND METHODS We systematically reviewed the literature using PubMed, Lilacs and Scielo, as well as manual bibliographical reference search of the studies. According to the Medical Subject Headings of the National Library of Medicine (MeSH), "childhood cancer", "ghrelin" and "leptin" were used as descriptors. RESULTS Fifteen studies were included in this systematic review published in English, from 2000 to 2015. A total of 863 patients were evaluated, ages ranging from 0 to 21 years, and most of the studies reported on children and adolescents with acute lymphoblastic leukemia (ALL) survivors. Most studies analyzed leptin levels; only two studies evaluated levels of ghrelin. CONCLUSION This review confirms that changes in the responses of the ghrelin and leptin hormones in children and adolescents with cancer are quite diverse, probably due to the different types of cancer observed, different treatments performed and biological characteristics of this age group.
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6.
Obesity as the Sequel of Childhood Stunting: Ghrelin and GHSR Gene Polymorphism Explained.
Muhammad, HFL
Acta medica Indonesiana. 2018;(2):159-164
Abstract
Stunting or short stature in children is a significant nutritional problem in developing and underdeveloped countries. Stunting during childhood might affect brain development and impair development cognitive function. Additionally, this condition associated with the increased risk for obesity during adulthood. Several studies have shown that the increment risk of obesity and overweight in children with a short stature was due to their metabolic efficiency. Children with stunting have lower resting energy expenditure compared to non stunting children. Additionally, stunted children has higher respiratory quotient and carbohydrate oxidation but lower fat oxidation compared to non-stunting children. These results might explain why stunted children easily become obese, which is due to lower fat oxidation and leading to tendency to store fat.This review discussed the current status on studies in the nutrigenetic aspects of the relationship between stunting in the childhood and obesity in adulthood. I hypothesized that stunted children are more likely to become obese in their later life because they have lower metabolic rate and higher tendency of fat storage. There are several candidate genes and pathway involved in obesity and I suspected that ghrelin and its receptor growth hormone secretague receptor (GHSR) were responsible.
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7.
Ghrelin Signaling in Immunometabolism and Inflamm-Aging.
Fang, C, Xu, H, Guo, S, Mertens-Talcott, SU, Sun, Y
Advances in experimental medicine and biology. 2018;:165-182
Abstract
Intracellular changes in immune cells lead to metabolic dysfunction, which is termed immunometabolism. Chronic inflammation is a hallmark of aging; this phenomenon is described as inflamm-aging. Immunometabolism and inflamm-aging are closely linked to obesity, insulin resistance, type 2 diabetes (T2D), cardiovascular diseases, and cancers, which consequently reduce life span and health span of the elderly. Ghrelin is an orexigenic hormone that regulates appetite and food intake. Ghrelin's functions are mediated through its receptor, growth hormone secretagogue receptor (GHS-R). Ghrelin and GHS-R have important roles in age-associated obesity, insulin resistance, and T2D. In this chapter, we have discussed the roles of ghrelin signaling in diet-induced obesity and normal aging as it relates to energy metabolism and inflammation in key metabolic tissues and organs. The new findings reveal that ghrelin signaling is an important regulatory mechanism for immunometabolism and inflamm-aging. Ghrelin signaling offers an exciting novel therapeutic strategy for treatment of obesity and insulin resistance of the elderly.
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8.
Effect of green tea on plasma leptin and ghrelin levels: A systematic review and meta-analysis of randomized controlled clinical trials.
Haghighatdoost, F, Nobakht M Gh, BF, Hariri, M
Nutrition (Burbank, Los Angeles County, Calif.). 2018;:17-23
Abstract
OBJECTIVE The purpose of this study was to conduct a meta-analysis of randomized controlled trials (RCTs) to assess the effect of green tea on serum leptin and ghrelin concentrations. METHODS We searched PubMed, ISI Web of Science, Scopus, and Google scholar databases up to December 2016. The searches included RCTs conducted in human adults, and studies on the effect of green tea and green tea extract on serum leptin and ghrelin concentrations as outcome variables. Weighted mean differences (WMDs) and standard errors (SEs) of changes in serum ghrelin and leptin levels were calculated. The random effects model was used to derive the summary mean estimates with their corresponding SEs. RESULTS Eleven RCTs were eligible to be included in the systematic review and the meta-analysis. Our analysis indicated that green tea did not significantly affect leptin and ghrelin concentrations in comparison to placebo (WMD = 1.28 ng/mL, 95% confidence interval: -0.49 to 3.05; P = 0.156, and WMD = 21.49 pg/mL, 95% confidence interval: -40.86 to 83.84; P = 0.499, respectively). However, green tea was associated with an increase in leptin concentration in studies that lasted for more than 12 wk and an increase in ghrelin in women and non-Asians. CONCLUSIONS Green tea or green tea extract might not be able to change circulatory leptin and ghrelin levels, especially with short-term interventions. More RCTs with longer duration of treatment and higher doses are necessary to assess green tea's effect on fat mass and obesity hormones.
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9.
Acute and Chronic Effects of Exercise on Appetite, Energy Intake, and Appetite-Related Hormones: The Modulating Effect of Adiposity, Sex, and Habitual Physical Activity.
Dorling, J, Broom, DR, Burns, SF, Clayton, DJ, Deighton, K, James, LJ, King, JA, Miyashita, M, Thackray, AE, Batterham, RL, et al
Nutrients. 2018;(9)
Abstract
Exercise facilitates weight control, partly through effects on appetite regulation. Single bouts of exercise induce a short-term energy deficit without stimulating compensatory effects on appetite, whilst limited evidence suggests that exercise training may modify subjective and homeostatic mediators of appetite in directions associated with enhanced meal-induced satiety. However, a large variability in responses exists between individuals. This article reviews the evidence relating to how adiposity, sex, and habitual physical activity modulate exercise-induced appetite, energy intake, and appetite-related hormone responses. The balance of evidence suggests that adiposity and sex do not modify appetite or energy intake responses to acute or chronic exercise interventions, but individuals with higher habitual physical activity levels may better adjust energy intake in response to energy balance perturbations. The effect of these individual characteristics and behaviours on appetite-related hormone responses to exercise remains equivocal. These findings support the continued promotion of exercise as a strategy for inducing short-term energy deficits irrespective of adiposity and sex, as well as the ability of exercise to positively influence energy balance over the longer term. Future well-controlled studies are required to further ascertain the potential mediators of appetite responses to exercise.
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10.
Searching for Evidence of an Anti-Inflammatory Diet in Children: A Systematic Review of Randomized Controlled Trials for Pediatric Obesity Interventions With a Focus on Leptin, Ghrelin, and Adiponectin.
Lewis, KA, Brown, SA
Biological research for nursing. 2017;(5):511-530
Abstract
PROBLEM To address the complex phenomenon of pediatric obesity, one must understand the physiological mechanisms regulating energy intake and inflammation. The peptide hormones leptin, ghrelin, and adiponectin are involved in both, but their functions are dysregulated in obesity. The purpose of this systematic review is (1) to characterize studies of nutrition interventions for weight management in children who measure these peptides as outcomes, (2) to assess risk of bias in the studies, and (3) to determine the relationships between these peptides and body mass index (BMI). Eligibility Criteria: Peer-reviewed articles written in English, published in 2001-2016, and describing randomized controlled trials of pediatric interventions involving a nutrition component with the outcome measures leptin, ghrelin, and/or adiponectin were included. Articles were excluded if the intervention involved pharmaceuticals, supplements, infant formula, breastfeeding, or surgery. SAMPLE The 25 international studies represented 2,153 obese children. RESULTS Ten diets were identified. Successful interventions included both structured exercise and hypocaloric dietary components, with or without counseling, resistance training, or medical components. Direct measures of adiposity were used in 69% of studies. Comparison group designs were disparate. Leptin levels decreased as BMI decreased. Evidence regarding the relationships of ghrelin and adiponectin with BMI was inconclusive. CONCLUSIONS Despite known effects of maturation on hormones, studies did not consistently differentiate findings by maturational stage. Common anti-inflammatory and disease risk modification diets were missing or underrepresented. Studies that include children with comorbidities are needed. BMI and leptin levels have a positive relationship, but evidence on ghrelin and adiponectin was inconclusive.