-
1.
Meta-analysis of ghrelin alterations in schizophrenia: Effects of olanzapine.
Goetz, RL, Miller, BJ
Schizophrenia research. 2019;:21-26
Abstract
OBJECTIVE Schizophrenia is associated with an increased prevalence of the metabolic syndrome. Patients receiving antipsychotic medications, including olanzapine, are at further risk. Ghrelin is an appetite-stimulating peptide hormone, although whether blood levels are altered by antipsychotic treatment, remains unclear. We performed a systematic review and meta-analysis comparing blood ghrelin levels in patients with schizophrenia before and after treatment with olanzapine. METHOD Two authors independently searched major electronic databases from inception until February 2018 for studies measuring blood ghrelin levels among patients with schizophrenia before and after olanzapine therapy. Random effects meta-analysis calculating standardized mean difference (SMD) and 95% confidence intervals (CI) and meta-regression analyses were performed. RESULTS Six studies met the inclusion criteria. Across these studies, there were 111 patients with schizophrenia (mean age 40, 85% male, baseline BMI 22, and endpoint BMI 23). Olanzapine treatment (mean [standard deviation] duration = 12.3 [7.6] weeks) was associated with a significant decrease in blood ghrelin levels with a medium effect size (SMD = -0.48, 95% CI -0.88 to -0.08, p = 0.018). Age, sex, baseline BMI, geography, olanzapine dose and duration, year of publication, study quality, inpatient status, and antipsychotic washout did not moderate this association. CONCLUSION Our results suggest that in patients with schizophrenia, olanzapine therapy is associated with decreased blood ghrelin levels, a paradoxical phenomenon known to occur in obesity. Future studies should investigate the contribution of dietary factors (e.g., caloric intake) and physical activity to this association, as well as the effects of other antipsychotics on ghrelin levels.
-
2.
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.
-
3.
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.
-
4.
Gastrointestinal hormones and polycystic ovary syndrome.
Ma, J, Lin, TC, Liu, W
Endocrine. 2014;(3):668-78
Abstract
Polycystic ovary syndrome (PCOS) is an endocrine disease of women in reproductive age. It is characterized by anovulation and hyperandrogenism. Most often patients with PCOS have metabolic abnormalities such as dyslipidemia, insulin resistance, and glucose intolerance. It is not surprising that obesity is high prevalent in PCOS. Over 60 % of PCOS women are obese or overweight. Modulation of appetite and energy intake is essential to maintain energy balance and body weight. The gastrointestinal tract, where nutrients are digested and absorbed, plays a central role in energy homeostasis. The signals from the gastrointestinal tract arise from the stomach (ghrelin release), proximal small intestine (CCK release), and distal small intestine (GLP-1 and PYY) in response to food. These hormones are recognized as "appetite regulatory hormones." Weight loss is the key in the treatments of obese/overweight patients with PCOS. However, current non-pharmacologic management of body weight is hard to achieve. This review highlighted the gastrointestinal hormones, and discussed the potential strategies aimed at modifying hormones for treatment in PCOS.
-
5.
Circulating leptin, resistin, adiponectin, visfatin, adipsin and ghrelin levels and insulin resistance in postmenopausal women with and without the metabolic syndrome.
Chedraui, P, Pérez-López, FR, Escobar, GS, Palla, G, Montt-Guevara, M, Cecchi, E, Genazzani, AR, Simoncini, T, ,
Maturitas. 2014;(1):86-90
Abstract
OBJECTIVE To measure serum levels of adipsin, leptin, resistin, adiponectin, visfatin, ghrelin and insulin in postmenopausal women screened for the metabolic syndrome (METS). METHODS Serum of 100 postmenopausal women was analyzed using multiplex technology for the mentioned analytes. In addition, values for the homeostasis model assessment of insulin resistance (HOMA-IR) were calculated. Comparisons were performed in accordance to the presence or not of the METS and each of its components. Criteria of the American Heart Association were used to define the METS. RESULTS Age and time since menopause onset were similar in women with the METS (n=57) as compared to those without the syndrome (n=43). METS women displayed significantly higher levels of adipsin, leptin, resistin, insulin and HOMA-IR values and lower adiponectin levels. These differences were mainly observed among women with abdominal obesity, independent of fulfilling METS criteria or not. In this same sense, lower adiponectin levels significantly related to low HDL-C and high triglyceride levels; and higher insulin and HOMA-IR values related to high triglyceride and glucose levels, respectively. CONCLUSION In this sample, postmenopausal women with the METS displayed higher insulin and adipokine levels. These were mainly related to abdominal obesity and metabolic and lipid abnormalities. More research is warranted in this regard.
-
6.
Short-term intake of a Japanese-style healthy lunch menu contributes to prevention and/or improvement in metabolic syndrome among middle-aged men: a non-randomized controlled trial.
Inoue, H, Sasaki, R, Aiso, I, Kuwano, T
Lipids in health and disease. 2014;:57
Abstract
BACKGROUND Metabolic syndrome is now widely appreciated as a cluster of metabolic abnormalities such as visceral obesity, hypertension, hyperglycemia and dyslipidemia. To date, incidence of metabolic syndrome is continuously increasing worldwide.In addition, low vegetable consumption has recently become a serious issue in Japan. Furthermore, Japan is facing a shortfall in places offering food that can help prevent metabolic syndrome in the first place. Our study is designed to influence these developments. We conducted a non-randomized controlled trial by offering a Japanese-style healthy lunch menu to middle-aged men in a workplace cafeteria. This menu was designed to prevent and reduce metabolic syndrome. METHODS This intervention study took the form of a non-randomized controlled trial. Participants chose the control or intervention group. The control group consumed their habitual lunches without restriction and only nutrient contents were assessed. The intervention group received a Japanese-style healthy lunch at a workplace cafeteria for 3 months. The participants worked in offices at a city hall and mostly had low levels of physical activity. Data of 35 males (control group: 7 males, intervention group: 28 males, mean age: 47.2 ± 7.9 years) were collected and analyzed. RESULTS We obtained an effective outcome by demonstrating that ongoing intake of a Japanese-style healthy lunch decreased blood pressure and serum lipids and increased plasma ghrelin levels. The results grew more pronounced as intake of Japanese-style healthy lunches increased in frequency. CONCLUSIONS This study presents new empirical data as a result of an original intervention program undertaken in Japan. A Japanese-style healthy lunch menu containing many vegetables consumed can help prevent and/or improve metabolic syndrome.
-
7.
Prader-Willi syndrome as a model of human hyperphagia.
Tauber, M, Diene, G, Mimoun, E, Çabal-Berthoumieu, S, Mantoulan, C, Molinas, C, Muscatelli, F, Salles, JP
Frontiers of hormone research. 2014;:93-106
Abstract
Prader-Willi syndrome (PWS), first described in 1956, is considered as a paradigm of a neurodevelopmental disorder with severe and early obesity with hyperphagia and impaired satiety. The improved knowledge in the natural history and recent data on genetics offer new perspectives for understanding the metabolic and endocrine dysfunctions and possibly for treatment. Natural history of the disease has been described due to the early diagnosis performed in the first months of life and various nutritional phases have been described. In addition, there is clear evidence that the abnormal feeding behavior is included in the behavioral problems. Brain imaging studies have shown that some brain regions may be important in PWS. The role of SNORD116 gene cluster is detailed and its links with circadian rhythm and brain and hypothalamus development. Pathophysiology of the abnormal ghrelin levels and of OT dysfunction is documented. While no effect on appetite and weight regulation has been reported with ghrelin antagonists, OT has been shown to improve some of the behavioral problems in adults. We discuss our hypothesis of an abnormal ghrelin/OT/dopamine pathway which may explain the switch of nutritional phases and behavior. These new aspects offer an opportunity for therapeutic use and possible early intervention.
-
8.
Effects of a brown beans evening meal on metabolic risk markers and appetite regulating hormones at a subsequent standardized breakfast: a randomized cross-over study.
Nilsson, A, Johansson, E, Ekström, L, Björck, I
PloS one. 2013;(4):e59985
Abstract
BACKGROUND Dietary prevention strategies are increasingly recognized as essential to combat the current epidemic of obesity and related metabolic disorders. The purpose of the present study was to evaluate the potential prebiotic effects of indigestible carbohydrates in Swedish brown beans (Phaseolus vulgaris var. nanus) in relation to cardiometabolic risk markers and appetite regulating hormones. METHODS Brown beans, or white wheat bread (WWB, reference product) were provided as evening meals to 16 healthy young adults in a randomised crossover design. Glucose, insulin, appetite regulatory hormones, GLP-1, GLP-2, appetite sensations, and markers of inflammation were measured at a following standardised breakfast, that is at 11 to 14 h post the evening meals. Additionally, colonic fermentation activity was estimated from measurement of plasma short chain fatty acids (SCFA, including also branched chain fatty acids) and breath hydrogen (H2) excretion. RESULTS An evening meal of brown beans, in comparison with WWB, lowered blood glucose (-15%, p<0.01)- and insulin (-16%, p<0.05) responses, increased satiety hormones (PYY 51%, p<0.001), suppressed hunger hormones (ghrelin -14%, p<0.05), and hunger sensations (-15%, p = 0.05), increased GLP-2 concentrations (8.4%, p<0.05) and suppressed inflammatory markers (IL-6 -35%, and IL-18 -8.3%, p<0.05) at a subsequent standardised breakfast. Breath H2 (141%, p<0.01), propionate (16%, p<0.05), and isobutyrate (18%, P<0.001) were significantly increased after brown beans compared to after WWB, indicating a higher colonic fermentative activity after brown beans. CONCLUSIONS An evening meal with brown beans beneficially affected important measures of cardiometabolic risk and appetite regulatory hormones, within a time frame of 11-14 h, in comparison to a WWB evening meal. Concentrations of plasma SCFA and H2 were increased, indicating involvement of colonic fermentation. Indigestible colonic substrates from brown beans may provide a preventive tool in relation to obesity and the metabolic syndrome. TRIAL REGISTRATION ClinicalTrials.gov NCT01706042.
-
9.
The growth hormone secretagogue receptor (Ghs-R).
Laviano, A, Molfino, A, Rianda, S, Rossi Fanelli, F
Current pharmaceutical design. 2012;(31):4749-54
Abstract
The growth hormone secretagogue receptor (GHS-R) is a component of the ghrelin signaling pathway and is involved in mediating the pleiotropic effects of ghrelin. Two isoforms have been identified, but only GHS-R1a binds with acyl ghrelin and transduces its message. However, the inactive variant of GHS-R, GHS-R1b, appears to play a critical role in modulating the activity of GHS-R1a by forming heterodimeric complexes which attenuates trafficking of the active variant to the cell surface. The molecular mechanisms of signal transduction are complex and are specific of the tissues where GHS-R1a is expressed. The potent induction of GH secretion and the stimulation of appetite are the most intensively studied functions of GHS-R1a. However, the tissue distribution of GHS-R1a extends beyond the pituitary and the hypothalamus, and reflects the different biological functions of the ghrelin/GHS-R system. GHS-R1a is also expressed in other brain areas, in the pancreas, adipose tissue, immune cells and cardiovascular system, and modulates learning and memory, glucose and lipid metabolism, inflammatory response and cardiac performance. The pleiotropic effects of the ghrelin/GHS-R system suggest their exploitation to prevent and treat a number of clinical conditions. Among many other syndromes and diseases, cancer cachexia, aging related cognitive decline, obesity and diabetes may significantly benefit from the use of GHS-R1a agonists or antagonists.
-
10.
Paediatric endocrine aspects of ghrelin.
Lim, CT, Korbonits, M
Pediatric endocrinology reviews : PER. 2012;(3):628-38
Abstract
Ghrelin is a 28 amino-acid brain-gut peptide that is well-known for its orexigenic and metabolic effects leading to an overall positive energy balance. It stimulates appetite and growth hormone release via the GHS-R1a receptors. GOAT has been identified as the enzyme that acylates ghrelin, which is important for its endocrine function. The ghrelin/GHS-R/GOAT system has been studied extensively in view of its association with several endocrine diseases and the potential of developing an effective treatment. These include obesity, Prader-Willi syndrome, anorexia nervosa and diabetes mellitus. Ghrelin system has also been associated with growth and stature. All these conditions can affect children and have a significant impact on the quality of health and life prognosis. In this review, we look into the association of ghrelin with appetite, growth and metabolic disorders in children.