RESUMEN
Extracellular acyl-coenzyme A binding protein [ACBP encoded by diazepam binding inhibitor (DBI)] is a phylogenetically ancient appetite stimulator that is secreted in a nonconventional, autophagy-dependent fashion. Here, we show that low ACBP/DBI plasma concentrations are associated with poor prognosis in patients with anorexia nervosa, a frequent and often intractable eating disorder. In mice, anorexia induced by chronic restraint stress (CRS) is accompanied by a reduction in circulating ACBP/DBI concentrations. We engineered a chemical-genetic system for the secretion of ACBP/DBI through a biotin-activatable, autophagy-independent pathway. In transgenic mice expressing this system in hepatocytes, biotin-induced elevations in plasma ACBP/DBI concentrations prevented anorexia induced by CRS or chemotherapeutic agents including cisplatin, doxorubicin, and paclitaxel. ACBP/DBI reversed the CRS or cisplatin-induced increase in plasma lipocalin-2 concentrations and the hypothalamic activation of anorexigenic melanocortin 4 receptors, for which lipocalin-2 is an agonist. Daily intravenous injections of recombinant ACBP/DBI protein or subcutaneous implantation of osmotic pumps releasing recombinant ACBP/DBI mimicked the orexigenic effects of the chemical-genetic system. In conclusion, the supplementation of extracellular and peripheral ACBP/DBI might constitute a viable strategy for treating anorexia.
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Anorexia , Inhibidor de la Unión a Diazepam , Animales , Inhibidor de la Unión a Diazepam/metabolismo , Anorexia/tratamiento farmacológico , Anorexia/metabolismo , Humanos , Ratones Transgénicos , Ratones , Anorexia Nerviosa/metabolismo , Anorexia Nerviosa/tratamiento farmacológico , Lipocalina 2/metabolismo , Lipocalina 2/sangre , Hipotálamo/metabolismo , Masculino , Femenino , Ratones Endogámicos C57BL , Restricción Física , Hepatocitos/metabolismo , Hepatocitos/efectos de los fármacosRESUMEN
Mammalian hibernators survive prolonged periods of cold and resource scarcity by temporarily modulating normal physiological functions, but the mechanisms underlying these adaptations are poorly understood. The hibernation cycle of thirteen-lined ground squirrels (Ictidomys tridecemlineatus) lasts for 5-7 months and comprises weeks of hypometabolic, hypothermic torpor interspersed with 24-48-h periods of an active-like interbout arousal (IBA) state. We show that ground squirrels, who endure the entire hibernation season without food, have negligible hunger during IBAs. These squirrels exhibit reversible inhibition of the hypothalamic feeding center, such that hypothalamic arcuate nucleus neurons exhibit reduced sensitivity to the orexigenic and anorexigenic effects of ghrelin and leptin, respectively. However, hypothalamic infusion of thyroid hormone during an IBA is sufficient to rescue hibernation anorexia. Our results reveal that thyroid hormone deficiency underlies hibernation anorexia and demonstrate the functional flexibility of the hypothalamic feeding center.
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Anorexia , Ghrelina , Hibernación , Hipotálamo , Sciuridae , Animales , Hibernación/fisiología , Sciuridae/fisiología , Anorexia/fisiopatología , Anorexia/metabolismo , Hipotálamo/metabolismo , Ghrelina/metabolismo , Ghrelina/deficiencia , Leptina/deficiencia , Leptina/metabolismo , Núcleo Arqueado del Hipotálamo/metabolismo , Neuronas/metabolismo , Neuronas/fisiología , Masculino , Hormonas Tiroideas/metabolismo , Nivel de Alerta/fisiología , Femenino , Estaciones del Año , Conducta Alimentaria/fisiologíaRESUMEN
There is inconsistent evidence relating to the effects of megestrol acetate (MA) supplementation on cancer patients suffering from anorexia-cachexia syndrome. This review aimed to examine the dose-response effect of MA supplementation in patients with cancer-associated anorexia/cachexia. Relevant keywords were searched in PubMed, Scopus and ISI Web of Science from inception to June 2023 for randomized controlled trials (RCTs) examining the effect of MA on pathologies in patients with cancer-associated cachexia. Our primary outcomes were changes in body weight and appetite. However, fatigue and quality of life were secondary outcomes. The mean difference (MD) and 95% confidence interval (95% CI) were estimated using the random-effects method. Thirteen trials comprising 1229 participants (mean age 60 years) were identified. The results of our highest versus lowest analysis revealed that MA supplementation was not associated with any increase in body weight (MD: 0.64 kg, 95% CI [-0.11, 1.38], P = 0.093, I2 = 69.1%; GRADE = very low certainty). Twelve trials, including 14 effect sizes derived from 1369 patients (intervention = 689, control = 680), provided data on the effect of MA on body weight. Subgroup analyses showed a significant increase in body weight following short-term intervention (≤8 weeks) and a combination of radiation/chemotherapy as concurrent treatment. A linear dose-response meta-analysis indicated that each 200 mg/day increment in MA consumption had a significant increase in weight gain (MD: 0.44; 95% CI [0.13, 0.74], P = 0.005; I2 = 97.1%); however, the magnitude of the effect was small. MA administration significantly affected the quality of life based on pooled effect sizes (MD: 1.15, 95% CI [0.76, 1.54], P < 0.001, I2 = 0%; n = 2 RCTs including 176 patients; GRADE = very low certainty). However, no significant effect of MA supplementation was observed on appetite (MD: 0.29, 95% CI [-0.05, 0.64], P = 0.096, I2 = 18.3%; n = 3 RCTs including 163 patients; GRADE = very low certainty) and fatigue (MD: 0.14, 95% CI [-0.09, 0.36], P = 0.236, I2 = 0%; n = 2 RCTs including 300 patients; GRADE = very low certainty). With very low certainty of the evidence, MA supplementation may not lead to a significantly increased weight gain and other outcomes.
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Anorexia , Caquexia , Suplementos Dietéticos , Acetato de Megestrol , Neoplasias , Humanos , Caquexia/etiología , Caquexia/tratamiento farmacológico , Acetato de Megestrol/uso terapéutico , Acetato de Megestrol/farmacología , Neoplasias/complicaciones , Anorexia/etiología , Anorexia/tratamiento farmacológico , Calidad de Vida , Relación Dosis-Respuesta a Droga , Peso CorporalRESUMEN
Food intake behavior is under the tight control of the central nervous system. Most studies to date focus on the contribution of neurons to this behavior. However, although previously overlooked, astrocytes have recently been implicated to play a key role in feeding control. Most of the recent literature has focused on astrocytic contribution in the hypothalamus or the dorsal vagal complex. The contribution of astrocytes located in the lateral parabrachial nucleus (lPBN) to feeding behavior control remains poorly understood. Thus, here, we first investigated whether activation of lPBN astrocytes affects feeding behavior in male and female rats using chemogenetic activation. Astrocytic activation in the lPBN led to profound anorexia in both sexes, under both ad-libitum feeding schedule and after a fasting challenge. Astrocytes have a key contribution to glutamate homeostasis and can themselves release glutamate. Moreover, lPBN glutamate signaling is a key contributor to potent anorexia, which can be induced by lPBN activation. Thus, here, we determined whether glutamate signaling is necessary for lPBN astrocyte activation-induced anorexia, and found that pharmacological N-methyl D-aspartate (NMDA) receptor blockade attenuated the food intake reduction resulting from lPBN astrocyte activation. Since astrocytes have been shown to contribute to feeding control by modulating the feeding effect of peripheral feeding signals, we further investigated whether lPBN astrocyte activation is capable of modulating the anorexic effect of the gut/brain hormone, glucagon like peptide -1, as well as the orexigenic effect of the stomach hormone - ghrelin, and found that the feeding effect of both signals is modulated by lPBN astrocytic activation. Lastly, we found that lPBN astrocyte activation-induced anorexia is affected by a diet-induced obesity challenge, in a sex-divergent manner. Collectively, current findings uncover a novel role for lPBN astrocytes in feeding behavior control.
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Astrocitos , Ingestión de Alimentos , Núcleos Parabraquiales , Animales , Astrocitos/metabolismo , Astrocitos/fisiología , Masculino , Femenino , Ratas , Ingestión de Alimentos/fisiología , Núcleos Parabraquiales/fisiología , Anorexia/metabolismo , Conducta Alimentaria/fisiología , Ratas Sprague-Dawley , Ácido Glutámico/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismoRESUMEN
OBJECTIVE: In response to bacterial inflammation, anorexia of acute illness is protective and is associated with the induction of fasting metabolic programs such as ketogenesis. Forced feeding during the anorectic period induced by bacterial inflammation is associated with suppressed ketogenesis and increased mortality. As ketogenesis is considered essential in fasting adaptation, we sought to determine the role of ketogenesis in illness-induced anorexia. METHODS: A mouse model of inducible hepatic specific deletion of the rate limiting enzyme for ketogenesis (HMG-CoA synthase 2, Hmgcs2) was used to investigate the role of ketogenesis in endotoxemia, a model of bacterial inflammation, and in prolonged starvation. RESULTS: Mice deficient of hepatic Hmgcs2 failed to develop ketosis during endotoxemia and during prolonged fasting. Surprisingly, hepatic HMGCS2 deficiency and the lack of ketosis did not affect survival, glycemia, or body temperature in response to endotoxemia. Mice with hepatic ketogenic deficiency also did not exhibit any defects in starvation adaptation and were able to maintain blood glucose, body temperature, and lean mass compared to littermate wild-type controls. Mice with hepatic HMGCS2 deficiency exhibited higher levels of plasma acetate levels in response to fasting. CONCLUSIONS: Circulating hepatic-derived ketones do not provide protection against endotoxemia, suggesting that alternative mechanisms drive the increased mortality from forced feeding during illness-induced anorexia. Hepatic ketones are also dispensable for surviving prolonged starvation in the absence of inflammation. Our study challenges the notion that hepatic ketogenesis is required to maintain blood glucose and preserve lean mass during starvation, raising the possibility of extrahepatic ketogenesis and use of alternative fuels as potential means of metabolic compensation.
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Hidroximetilglutaril-CoA Sintasa , Cetosis , Hígado , Inanición , Animales , Ratones , Hígado/metabolismo , Inanición/metabolismo , Hidroximetilglutaril-CoA Sintasa/metabolismo , Hidroximetilglutaril-CoA Sintasa/genética , Masculino , Cetosis/metabolismo , Endotoxemia/metabolismo , Adaptación Fisiológica , Cuerpos Cetónicos/metabolismo , Glucemia/metabolismo , Ratones Endogámicos C57BL , Ayuno/metabolismo , Ratones Noqueados , Anorexia/metabolismoRESUMEN
T-2 toxin is one of trichothecene mycotoxins, which can impair appetite and decrease food intake. However, the specific mechanisms for T-2 toxin-induced anorexia are not fully clarified. Multiple research results had shown that gut microbiota have a significant effect on appetite regulation. Hence, this study purposed to explore the potential interactions of the gut microbiota and appetite regulate factors in anorexia induced by T-2 toxin. The study divided the mice into control group (CG, 0â¯mg/kg BW T-2 toxin) and T-2 toxin-treated group (TG, 1â¯mg/kg BW T-2 toxin), which oral gavage for 4 weeks, to construct a subacute T-2 toxin poisoning mouse model. This data proved that T-2 toxin was able to induce an anorexia in mice by increased the contents of gastrointestinal hormones (CCK, GIP, GLP-1 and PYY), neurotransmitters (5-HT and SP), as well as pro-inflammatory cytokines (IL-1ß, IL-6 and TNF-α) in serum of mice. T-2 toxin disturbed the composition of gut microbiota, especially, Faecalibaculum and Allobaculum, which was positively correlated with CCK, GLP-1, 5-HT, IL-1ß, IL-6 and TNF-α, which played a certain role in regulating host appetite. In conclusion, gut microbiota changes (especially an increase in the abundance of Faecalibaculum and Allobaculum) promote the upregulation of gastrointestinal hormones, neurotransmitters, and pro-inflammatory cytokines, which may be a potential mechanism of T-2 toxin-induced anorexia.
Asunto(s)
Anorexia , Microbioma Gastrointestinal , Toxina T-2 , Animales , Toxina T-2/toxicidad , Microbioma Gastrointestinal/efectos de los fármacos , Anorexia/inducido químicamente , Ratones , Citocinas/metabolismo , Hormonas Gastrointestinales/metabolismo , MasculinoRESUMEN
OBJECTIVE: Anorexia nervosa (AN) is characterized by hyperactivation of the hypothalamic-pituitary-adrenal axis and cognitive deficits. However, little is known about the rapid non-genomic stress response involvement. This study investigates the molecular, structural and behavioral signatures of the anorexic phenotype induction in female rats on stress-related mechanisms in the hippocampus. METHOD: Female adolescent rats, exposed to the combination of food restriction and wheel access, i.e., the activity-based anorexia (ABA) protocol, were sacrificed in the acute phase of the pathology (postnatal day [P]42) or following a 7-day recovery period (P49). RESULTS: ABA rats, in addition to body weight loss and increased wheel activity, alter their pattern of activity over days, showing increased food anticipatory activity, a readout of their motivation to engage in intense physical activity. Corticosterone plasma levels were enhanced at P42 while reduced at P49 in ABA rats. In the membrane fraction of the hippocampus, we found reduced glucocorticoid receptor levels together with reduced expression of caldesmon, n-cadherin and neuroligin-1, molecular markers of cytoskeletal stability and glutamatergic homeostasis. Accordingly, structural analyses revealed reduced dendritic spine density, a reduced number of mushroom-shaped spines, together with an increased number of thin-shaped spines. These events are paralleled by impairment in spatial memory measured in the spatial order object recognition test. These effects persisted even when body weight of ABA rats was restored. DISCUSSION: Our findings indicate that ABA induction orchestrates hippocampal maladaptive structural and functional plasticity, contributing to cognitive deficits, providing a putative mechanism that could be targeted in AN patients.
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Hipocampo , Animales , Femenino , Hipocampo/metabolismo , Ratas , Memoria Espacial/fisiología , Anorexia/metabolismo , Anorexia/fisiopatología , Anorexia/patología , Corticosterona/sangre , Estrés Psicológico/fisiopatología , Estrés Psicológico/metabolismo , Trastornos de la Memoria/fisiopatología , Trastornos de la Memoria/patología , Ratas Wistar , Receptores de Glucocorticoides/metabolismo , Anorexia Nerviosa/metabolismo , Anorexia Nerviosa/fisiopatología , Anorexia Nerviosa/patología , Modelos Animales de EnfermedadRESUMEN
Platinum-based chemotherapy drugs can lead to the development of anorexia, a detrimental effect on the overall health of cancer patients. However, managing chemotherapy-induced anorexia and subsequent weight loss remains challenging due to limited effective therapeutic strategies. Growth differentiation factor 15 (GDF15) has recently gained significant attention in the context of chemotherapy-induced anorexia. Here, we report that hepatic GDF15 plays a crucial role in regulating body weight in response to chemo drugs cisplatin and doxorubicin. Cisplatin and doxorubicin treatments induce hepatic Gdf15 expression and elevate circulating GDF15 levels, leading to hunger suppression and subsequent weight loss. Mechanistically, selective activation by chemotherapy of hepatic IRE1α-XBP1 pathway of the unfolded protein response (UPR) upregulates Gdf15 expression. Genetic and pharmacological inactivation of IRE1α is sufficient to ameliorate chemotherapy-induced anorexia and body weight loss. These results identify hepatic IRE1α as a molecular driver of GDF15-mediated anorexia and suggest that blocking IRE1α RNase activity offers a therapeutic strategy to alleviate the adverse anorexia effects in chemotherapy.
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Anorexia , Doxorrubicina , Endorribonucleasas , Factor 15 de Diferenciación de Crecimiento , Hígado , Proteínas Serina-Treonina Quinasas , Pérdida de Peso , Proteína 1 de Unión a la X-Box , Animales , Humanos , Ratones , Anorexia/inducido químicamente , Anorexia/metabolismo , Antineoplásicos/efectos adversos , Cisplatino/efectos adversos , Doxorrubicina/efectos adversos , Endorribonucleasas/metabolismo , Endorribonucleasas/genética , Factor 15 de Diferenciación de Crecimiento/efectos adversos , Factor 15 de Diferenciación de Crecimiento/genética , Factor 15 de Diferenciación de Crecimiento/metabolismo , Hígado/metabolismo , Hígado/efectos de los fármacos , Hígado/patología , Ratones Endogámicos C57BL , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Transducción de Señal/efectos de los fármacos , Respuesta de Proteína Desplegada/efectos de los fármacos , Pérdida de Peso/efectos de los fármacos , Proteína 1 de Unión a la X-Box/metabolismo , Proteína 1 de Unión a la X-Box/genéticaRESUMEN
BACKGROUND: This study aimed to explore the gut microbiota and inflammatory factor characteristics in major depressive disorder (MDD) patients with anorexia and to analyze the correlation between gut microbiota and inflammatory factors, anorexia, and HAMD scores. METHODS: 46 MDD patients and 46 healthy controls (HC) were included in the study. The 46 MDD patients were divided into two groups according to whether they had anorexia:20 MDD without anorexia (MDA0 group) and 26 MDD with anorexia (MDA1 group). We used the Hamilton Depression Scale-24 (HAMD-24) to evaluate the depression status of all participants and 16 S ribosomal RNA (16 S rRNA)sequencing to evaluate the composition of the gut microbiota. Inflammatory factors in peripheral blood such as C-reactive protein (CRP) were detected using enzyme-linked immunosorbent assay (ELISA). Spearman's correlation analysis was used to evaluate the correlation between gut microbiota and inflammatory factors, HAMD scores, and anorexia. RESULTS: 1). CRP was significantly higher in the MDA0, MDA1, than HC. 2). An analysis of α-diversity shows: the Simpson and Pielou indices of the HC group are higher than the MDA1 group (P < 0.05). 3). The ß-diversity analysis shows differences in the composition of microbial communities between the MDA0, MDA1, and HC group. 4). A correlation analysis showed that Blautia positively correlated with anorexia, HAMD scores, and CRP level, whereas Faecalibacterium, Bacteroides, Roseburia, and Parabacteroides negatively correlated with anorexia, HAMD scores, and CRP level. 5). The receiver operating characteristic (ROC) curve was drawn using the differential bacterial genera between MDD patients with or without anorexia as biomarkers to identify whether MDD patients were accompanied with anorexia, and its area under curve (AUC) was 0.85. The ROC curve was drawn using the differential bacterial genera between MDD patients with anorexia and healthy controls as biomarkers to diagnose MDD patients with anorexia, with its AUC was 0.97. CONCLUSION: This study suggested that MDD patients with anorexia had a distinct gut microbiota compared to healthy individuals, with higher level of CRP. Blautia was more abundant in MDD patients with anorexia and positively correlated with CRP, HAMD scores, and anorexia. The gut microbiota might have influenced MDD and anorexia through the inflammatory factor CRP.
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Anorexia , Proteína C-Reactiva , Trastorno Depresivo Mayor , Microbioma Gastrointestinal , Humanos , Microbioma Gastrointestinal/fisiología , Trastorno Depresivo Mayor/sangre , Trastorno Depresivo Mayor/microbiología , Femenino , Adulto , Masculino , Proteína C-Reactiva/análisis , Proteína C-Reactiva/metabolismo , Anorexia/microbiología , Anorexia/sangre , Inflamación/sangre , Persona de Mediana Edad , Estudios de Casos y Controles , ARN Ribosómico 16S/genética , Adulto JovenRESUMEN
GDF15 is a stress response cytokine and a distant member of the transforming growth factor beta (TGFß) superfamily, its levels increase in response to cell stress and certain diseases in the serum. To exert its effects, GDF15 binds to glial-derived neurotrophic factor (GDNF) receptor alpha-like (GFRAL), which was firstly identified in 2017 and highly expressed in the brain stem. Many studies have demonstrated that elevated serum GDF15 is associated with anorexia and weight loss. Herein, we focus on the biology of GDF15, specifically how this circulating protein regulates appetite and metabolism in influencing energy homeostasis through its actions on hindbrain neurons to shed light on its impact on diseases such as obesity and anorexia/cachexia syndromes. It works as an endocrine factor and transmits metabolic signals leading to weight reduction effects by directly reducing appetite and indirectly affecting food intake through complex mechanisms, which could be a promising target for the treatment of energy-intake disorders.
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Factor 15 de Diferenciación de Crecimiento , Enfermedades Metabólicas , Humanos , Factor 15 de Diferenciación de Crecimiento/metabolismo , Factor 15 de Diferenciación de Crecimiento/sangre , Animales , Enfermedades Metabólicas/metabolismo , Metabolismo Energético/fisiología , Obesidad/metabolismo , Anorexia/metabolismo , Apetito/fisiologíaRESUMEN
OBJECTIVE: The aim of this study was to investigate and evaluate the risk of dyspepsia and anorexia in patients with type 2 diabetes mellitus (T2DM) induced by glucagon-like peptide 1 receptor agonist (GLP-1 RA) hypoglycemic drugs. MATERIALS AND METHODS: We searched papers in PubMed, Web of Science, Cochrane Library, Google Scholar, CNKI, Wanfang, Embase, and VIP databases, and the retrieval time limit was set from the establishment of the database to May 2023. Randomized Controlled Trials (RCTs) were collected in which the subjects were T2DM patients, the intervention was GLP-1RA compared with placebo or traditional hypoglycemic drugs, and the outcome indicators included dyspepsia and anorexia. A meta-analysis and a network meta-analysis were performed. RESULTS: The results of the traditional meta-analysis showed that the risk of dyspepsia and anorexia of total GLP-1 RA was 3.01 and 2.56 times that of placebo, respectively. All types of GLP-1RA were compared with placebo and the results also showed a trend towards increased risk of digestive system adverse events (DSAEs). Among all interventions included, liraglutide was the one with the highest risk of dyspepsia in patients with T2DM, and dulaglutide was the one with the highest risk of anorexia. CONCLUSIONS: The results of the two meta-analyses are consistent, and both clearly show that GLP-1RA can increase the risk of dyspepsia and anorexia in T2DM patients.
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Anorexia , Diabetes Mellitus Tipo 2 , Dispepsia , Receptor del Péptido 1 Similar al Glucagón , Hipoglucemiantes , Humanos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/complicaciones , Receptor del Péptido 1 Similar al Glucagón/agonistas , Dispepsia/tratamiento farmacológico , Dispepsia/inducido químicamente , Hipoglucemiantes/efectos adversos , Hipoglucemiantes/uso terapéutico , Anorexia/inducido químicamente , Anorexia/tratamiento farmacológico , Metaanálisis en Red , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
PURPOSE OF REVIEW: The following review will highlight the development of anamorelin to treat cancer anorexia-cachexia syndrome (CACS) including the potential benefits, limitations, and future directions. RECENT FINDINGS: Ghrelin, a 28-amino acid peptide hormone, is secreted by the stomach mucosa and regulates appetite, promotes lipogenesis, increases body weight, improves gastric motility, reduces catabolic wasting and inflammation. Several randomized, double-blind, placebo-controlled clinical trials evaluating anamorelin, a ghrelin agonist, for the treatment of CACS have reported improvement in appetite and body composition including both lean body and fat mass; however, most studies noted no improvement in physical function as assessed by measuring non-dominant hand-grip strength. Common adverse effects of anamorelin include the development of diabetes mellitus, hyperglycemia, and less frequently, hepatic abnormalities and cardiovascular events including conduction abnormalities, hypertension, and ischemic cardiomyopathy. Anamorelin has the potential to stimulate appetite, improve gastric movement, and may have anti-inflammatory effects on patients with CACS. In patients with cancer, studies involving anamorelin combined with other multimodal treatments including nutrition counseling (branched chain amino acids, omega 3 fatty acids, and other nutrients), exercise, treatment of hormonal abnormalities including hypogonadism and hypovitaminosis D, and anti-inflammatory agents are needed. Compliance with multimodality treatment has been a barrier and future studies may need to incorporate motivational counseling to promote adherence.
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Anorexia , Caquexia , Neoplasias , Humanos , Caquexia/tratamiento farmacológico , Caquexia/etiología , Neoplasias/complicaciones , Neoplasias/tratamiento farmacológico , Anorexia/tratamiento farmacológico , Anorexia/etiología , Oligopéptidos/uso terapéutico , Glicina/uso terapéutico , Glicina/análogos & derivados , Ghrelina/uso terapéutico , Aminoácidos de Cadena Ramificada/uso terapéutico , HidrazinasRESUMEN
PURPOSE OF REVIEW: This focused, narrative review mostly describes our team's investigations into the potential inflammatory mechanisms that contribute to the development of cancer-related gastrointestinal (GI) mucositis and its associated symptoms. This review summarizes details of our clinical and preclinical findings to test the role of inflammation in the development and occurrence of these cancer-related conditions. RECENT FINDINGS: GI mucositis (GIM) is a common, distressing condition reported by cancer patients. GIM is often clustered with other behaviors including fatigue, pain, anorexia, depression, and diarrhea. It is hypothesized that there is a common biologic mechanism underpinning this symptom cluster. Our multi-platform investigations revealed that GIM and its associated cluster of behaviors may be triggered by local inflammation spreading systemically causing pro-inflammatory-mediated toxicities, leading to alterations in immune, metabolic, and nervous system functions and activities. For example, behavioral toxicities related to local irradiation for non-metastatic cancer may be triggered by mGluR5 activation influencing prolonged T cell as well as NF-κB transcription factor activities. Thus, interventions targeting inflammation and associated pathways may be a reasonable strategy to alleviate GIM and its symptom cluster. SUMMARY: GIM may be a sign of a broader systemic inflammatory response triggered by cancer or its treatment. Addressing GIM and its associated symptoms primarily involves supportive care strategies focused on relieving symptoms, promoting healing, and preventing complications.
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Mucositis , Neoplasias , Humanos , Neoplasias/complicaciones , Mucositis/etiología , Inflamación/fisiopatología , Depresión/etiología , Fatiga/etiología , Fatiga/fisiopatología , Receptor del Glutamato Metabotropico 5 , Síndrome de Respuesta Inflamatoria Sistémica/fisiopatología , Anorexia/etiología , Anorexia/fisiopatología , FN-kappa B/metabolismo , Diarrea/etiología , Enfermedades Gastrointestinales/etiología , Enfermedades Gastrointestinales/fisiopatología , Dolor/etiologíaRESUMEN
Nicotine use produces psychoactive effects, and chronic use is associated with physiological and psychological symptoms of addiction. However, chronic nicotine use is known to decrease food intake and body weight gain, suggesting that nicotine also affects central metabolic and appetite regulation. We recently showed that acute nicotine self-administration in nicotine-dependent animals produces a short-term increase in food intake, contrary to its long-term decrease of feeding behavior. As feeding behavior is regulated by complex neural signaling mechanisms, this study aimed to test the hypothesis that nicotine intake in animals exposed to chronic nicotine may increase activation of pro-feeding regions and decrease activation of pro-satiety regions to produce the acute increase in feeding behavior. FOS immunohistochemistry revealed that acute nicotine intake in nicotine self-administering animals increased activation of the pro-feeding arcuate and lateral hypothalamic nuclei and decreased activation of the pro-satiety parabrachial nucleus. Regional correlational analysis also showed that acute nicotine changes the functional connectivity of the hunger/satiety network. Further dissection of the role of the arcuate nucleus using electrophysiology found that putative POMC neurons in animals given chronic nicotine exhibited decreased firing following acute nicotine application. These brain-wide central signaling changes may contribute to the acute increase in feeding behavior we see in rats after acute nicotine and provide new areas of focus for studying both nicotine addiction and metabolic regulation.
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Encéfalo , Nicotina , Animales , Nicotina/farmacología , Masculino , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Ratas , Ratas Sprague-Dawley , Agonistas Nicotínicos/farmacología , Conducta Alimentaria/efectos de los fármacos , Proopiomelanocortina/metabolismo , Ingestión de Alimentos/efectos de los fármacos , Ingestión de Alimentos/fisiología , Autoadministración , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Proteínas Proto-Oncogénicas c-fos/metabolismo , Anorexia/inducido químicamenteRESUMEN
Anorexia of aging is a risk factor for malnutrition among older adults. This study aimed to evaluate the association between objective and subjective oral health and anorexia among independent older adults. This cross-sectional study targeted independent older adults aged ≥65 years who participated in the Japan Gerontological Evaluation Study conducted in 2022. The outcome variable was the presence of anorexia, as assessed by the Simplified Nutritional Appetite Questionnaire. Exposure variables were dental status (≥20 teeth, 10-19 teeth with/without dentures, and 0-9 teeth with/without dentures) as objective oral health and oral health-related quality of life measured by five items of the short version of the Oral Impacts on Daily Performances (OIDP) (eating, speaking, smiling, emotional stability, and enjoying with others) as subjective oral health. We fitted the Poisson regression model, including possible confounders, and estimated prevalence ratios (PRs) and 95% confidence intervals. Among 19,787 participants (mean age: 74.6 years [1SD = 6.2], male: 48.5%), 9.0% were classified as having anorexia. After adjusting possible confounders, those with ≤19 teeth had a higher proportion of experiencing anorexia compared to those with ≥20 teeth; however, the association was less pronounced among those with dentures (0-9 teeth with dentures: PR = 1.48 [1.31-1.68], and 0-9 teeth without dentures: PR = 2.08 [1.65-2.63]). Even after adjusting for dental status, each item of OIDP was significantly associated with the presence of anorexia (all p < 0.05). The results showed that both objective and subjective poor oral health were significantly associated with a higher probability of developing anorexia of aging. Therefore, improving both objective and subjective oral health through appropriate dental care could contribute to maintaining appetite in later life.
Asunto(s)
Anorexia , Salud Bucal , Calidad de Vida , Humanos , Masculino , Anciano , Femenino , Estudios Transversales , Japón/epidemiología , Anorexia/epidemiología , Anorexia/psicología , Anciano de 80 o más Años , Envejecimiento/psicología , Encuestas y Cuestionarios , Prevalencia , Evaluación Geriátrica/métodos , Apetito , Dentaduras , Pueblos del Este de AsiaRESUMEN
PURPOSE: We evaluated the efficacy of megestrol in improving chemotherapy-related anorexia by analyzing the related scales of taste alteration. METHODS: We conducted the current study on a group of advanced patients with cancer with two or more chemotherapy cycles. The chemotherapy-induced taste alteration scale (CiTAs) scale helped assess the megestrol effects on basic taste perception, aversive taste changes, unpleasant symptoms, and associated concerns. Furthermore, the Short Nutritional Assessment Questionnaire scale (SNAQ) helped measure the impact of megestrol on malnutrition likelihood in patients experiencing chemotherapy-induced anorexia. The World Health Organization Quality of Life (WHOQOL)-BREF Scale was used to evaluate the quality of life of participants, producing scores related to physical health, psychological well-being, environmental factors, and social relationships. RESULTS: The CiTAs scale assessment indicated that administering megestrol significantly enhanced taste perception among advanced patients with cancer undergoing chemotherapy. Notably, the megestrol group patients showed significantly higher Short Nutritional Assessment Questionnaire (SNAQ) scores than the control group. The megestrol group patients also exhibited higher physiological (PHYS) scores than their control group counterparts. However, this distinction was not statistically significant. The study findings indicate that patients who received megestrol demonstrated significantly higher scores in psychological (PSYCH) and environmental(ENVIR) domains than the control group. Furthermore, megestrol administration was associated with significantly elevated SOCIL and ENVIR levels in patients. CONCLUSION: The proficient efficacy evaluation of megestrol in enhancing appetite, mitigating malnutrition likelihood, and improving the quality of life of chemotherapy-induced anorexic patients can be achieved through taste-related scales.
Asunto(s)
Anorexia , Antineoplásicos , Neoplasias , Calidad de Vida , Humanos , Anorexia/inducido químicamente , Masculino , Femenino , Persona de Mediana Edad , Neoplasias/tratamiento farmacológico , Encuestas y Cuestionarios , Antineoplásicos/efectos adversos , Anciano , Adulto , Acetato de Megestrol/efectos adversos , Acetato de Megestrol/uso terapéutico , Acetato de Megestrol/administración & dosificación , Evaluación Nutricional , Estimulantes del Apetito/uso terapéutico , Estimulantes del Apetito/administración & dosificación , Estimulantes del Apetito/efectos adversos , Gusto/efectos de los fármacosRESUMEN
Leptin is an appetite-regulating adipokine that is reduced in patients with anorexia nervosa (AN), a psychiatric disorder characterized by self-imposed starvation, and has been linked to hyperactivity, a hallmark of AN. However, it remains unknown how leptin receptor (LepR) and its JAK2-STAT3 downstream pathway in extrahypothalamic brain areas, such as the dorsal (dHip) and ventral (vHip) hippocampus, crucial for spatial memory and emotion regulation, may contribute to the maintenance of AN behaviors. Taking advantage of the activity-based anorexia (ABA) model (i.e., the combination of food restriction and physical activity), we observed reduced leptin plasma levels in adolescent female ABA rats at the acute phase of the disorder [post-natal day (PND) 42], while the levels increased over control levels following a 7-day recovery period (PND49). The analysis of the intracellular leptin pathway revealed that ABA rats showed an overall decrease of the LepR/JAK2/STAT3 signaling in dHip at both time points, while in vHip we observed a transition from hypo- (PND42) to hyperactivation (PND49) of the pathway. These changes might add knowledge on starvation-induced fluctuations in leptin levels and in hippocampal leptin signaling as initial drivers of the transition from adaptative mechanisms to starvation toward the maintenance of aberrant behaviors typical of AN patients, such as perpetuating restraint over eating.
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Anorexia , Hipocampo , Janus Quinasa 2 , Leptina , Receptores de Leptina , Factor de Transcripción STAT3 , Transducción de Señal , Animales , Femenino , Janus Quinasa 2/metabolismo , Factor de Transcripción STAT3/metabolismo , Hipocampo/metabolismo , Leptina/sangre , Anorexia/etiología , Anorexia/metabolismo , Ratas , Receptores de Leptina/metabolismo , Anorexia Nerviosa/metabolismo , Anorexia Nerviosa/sangre , Modelos Animales de Enfermedad , Adaptación FisiológicaRESUMEN
Activity-based anorexia (ABA) is a rodent model of anorexia nervosa (AN) that induces several key components of AN, including voluntary reduction in food intake, reduced body weight, hyperactivity, and alterations to the hypothalamic-pituitary-adrenal (HPA) axis. Previous research has demonstrated persistently increased anxiety-like behavior in the elevated plus maze (EPM), a test measuring avoidance of novel and open areas in adult female rats that experienced ABA during adolescence and are weight-restored in adulthood. Whether the same behavioral effects of two bouts of adolescent ABA emerge in response to different anxiety-provoking stimuli, however, has not been explored. We used the social partition (SP), novelty suppressed feeding (NSF), marble burying, and EPM tests to explore whether two bouts of adolescent ABA have persistent effects on anxiety-like behavior in weight restored young adult female rats. One-way ANOVA analyses revealed that female rats that experienced two bouts of ABA during adolescence had increased anxiety-like behavior in the EPM and SP tests in young adulthood following weight restoration compared with controls. These data demonstrate that the enduring behavioral effects of two bouts of adolescent ABA are specific to particular anxiety-provoking stimuli and suggest that adolescent ABA has enduring effects on social relationships.
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Anorexia Nerviosa , Anorexia , Ratas , Animales , Femenino , Conducta Social , Ansiedad/etiología , Trastornos de Ansiedad , Modelos Animales de EnfermedadRESUMEN
Cancer-related anorexia-cachexia (CRAC) comprises one of the most common syndromes of advanced cancer patients. The prevalence of CRAC increases from 50% to 80% before death. CRAC is associated not only with impaired quality of life in patients and family members but also with shorter survival. The management of CRAC is a great challenge in clinical practice. There are no definite practice guidelines yet for the prevention and treatment of CRAC. A multimodal strategy is the most effective way to treat anorexia-cachexia. Numerous medications have been suggested and used in clinical trials, while others are still being studied on experimental animals. These medications include branched-chain amino acids, eicosapentaenoic acid, thalidomide, cytokine inhibitors, steroids, antiserotoninergic medications, and appetite stimulants. The benefits of supportive care interventions and the advancement of exciting new pharmacological medicines for anorexia-cachexia are becoming more widely recognized. Health care professionals need to be aware of the psychosocial and biological effects of anorexia-cachexia, even though knowledge of the underlying molecular causes of the disorder has advanced significantly.
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Anorexia , Caquexia , Neoplasias , Humanos , Anorexia/terapia , Anorexia/tratamiento farmacológico , Anorexia/etiología , Anorexia/fisiopatología , Neoplasias/complicaciones , Neoplasias/tratamiento farmacológico , Caquexia/terapia , Caquexia/etiología , Caquexia/fisiopatología , Caquexia/tratamiento farmacológico , AnimalesRESUMEN
BACKGROUND: Gastritis cystica profunda (GCP), commonly observed in remnant gastric anastomosis, is associated with developing gastric cancer. CASE: This case report describes a patient with GCP in a previously unoperated stomach that mimicked a pyloric submucosal tumor and caused anorexia, which is rare in clinical practice. PATIENT CONCERNS: A 72-year-old woman presented with loss of appetite and weight. DIAGNOSES: Gastroscopy detected a 20 mm diameter submucosal tumor near the pylorus. Computed tomography and magnetic resonance imaging identified a cystic lesion, unlike a usual submucosal tumor in the stomach. The diagnosis was difficult, even with endoscopic ultrasound-guided fine-needle aspiration. INTERVENTIONS: Surgery was performed for diagnosis and treatment. The lesion was resected using a submucosal dissection technique after an incision of the gastric wall during open laparotomy. Histopathological examination confirmed the diagnosis of GCP and revealed no dysplasia or cancer. OUTCOMES: Anorexia resolved after the surgery. Residual or recurrent lesions were not detected during follow-up examinations performed 1 year after surgery. LESSONS: GCP occurring in a previously unoperated stomach as a macroscopic lesion like a submucosal tumor causing some symptoms is rare. GCP is associated with a risk of developing cancer. Therefore, careful evaluation and management during treatment are required.