Hypothalamic hormone deficiency enables physiological anorexia in ground squirrels during hibernation.

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.

Lateral parabrachial nucleus astrocytes control food intake.

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.

The role of gut microbiota in anorexia induced by T-2 toxin.

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, 0 mg/kg BW T-2 toxin) and T-2 toxin-treated group (TG, 1 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.

Hepatic ketogenesis is not required for starvation adaptation in mice.

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.

Anamorelin for the Treatment of Cancer Anorexia-Cachexia Syndrome.

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.

Overview of growth differentiation factor 15 (GDF15) in metabolic diseases.

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.

Hepatic IRE1α-XBP1 signaling promotes GDF15-mediated anorexia and body weight loss in chemotherapy.

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.

Network meta-analysis of the risk of dyspepsia and anorexia in patients with type 2 diabetes mellitus induced by glucagon-like peptide 1 receptor agonist hypoglycemic drugs.

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.

Gut microbiota and inflammatory factor characteristics in major depressive disorder patients with anorexia.

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.

The association between objective and subjective oral health conditions and the presence of anorexia of aging among Japanese older Adults1.

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.

Anorexia-Induced Hypoleptinemia Drives Adaptations in the JAK2/STAT3 Pathway in the Ventral and Dorsal Hippocampus of Female Rats.

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.

A taste alteration-related scale assesses megestrol to improve chemotherapy-induced anorexia.

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.

Acute nicotine activates orectic and inhibits anorectic brain regions in rats exposed to chronic nicotine.

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.

Efficacy of probiotic supplements in improving the symptoms of psychosis, anxiety, insomnia, and anorexia due to amphetamine and methamphetamine use: a randomized clinical trial.

RATIONALE: Changes in the density and diversity of gut microbiota in chronic use of methamphetamine have been mentioned as contributors to psychotic and anxiety symptoms, sleep problems, and loss of appetite. OBJECTIVE: In this placebo-controlled clinical trial, we investigated the effect of the probiotic Lactobacillus Acidophilus in improving psychiatric symptoms among hospitalized patients with chronic methamphetamine use along with psychotic symptoms. METHODS: 60 inpatients with a history of more than 3 years of methamphetamine use, were randomly assigned to one of two groups receiving either a probiotic capsule or placebo along with risperidone for 8 weeks based on a simple randomization method. In weeks 0, 4, and 8, patients were evaluated using the Brief Psychiatric Rating Scale (BPRS), Beck Anxiety Inventory (BAI), Pittsburgh Sleep Quality Index (PSQI), Simple Appetite Nutritional Questionnaire (SANQ), and Body Mass Index (BMI). RESULTS: Compared to the control group, patients receiving probiotics had better sleep quality, greater appetite, and higher body mass index (there were significant interaction effects of group and time at Week 8 in these variables (t = -3.32, B = -1.83, p = .001, d = 0.89), (t = 10.50, B = 2.65, p <.001, d = 1.25) and (t = 3.40, B = 0.76, p <.001, d = 0.30), respectively. In terms of the improvement of psychotic and anxiety symptoms, there was no statistically significant difference between the two groups. CONCLUSIONS: The use of probiotics was associated with improved sleep quality, increased appetite, and increased body mass index in patients with chronic methamphetamine use. Conducting more definitive clinical trials with larger sample sizes and longer-term follow-up of cases is recommended.

Consequences of Anorexia of Aging in Hospital Settings: An Updated Review.

The anorexia of aging is a widespread problem amongst older people, particularly in the hospital setting with up to 60% affected. Despite its high prevalence anorexia often goes undiagnosed in hospital, due to a lack of standardized assessment and evidence-based management, but also lack of knowledge regarding consequences. This review summarizes current evidence for anorexia of aging specific to the hospital setting, giving an overview of correlates of appetite in hospital and consequences of anorexia. It highlights an overall scarcity of research on this important clinical problem for hospitalized cohorts. The few studies point to the importance of anorexia of aging in major health burdens for older people, namely malnutrition, sarcopenia and reduced physical performance, as well as higher mortality. Further research is needed to assess temporal sequence in pathways of causality and to develop effective interventions to combat anorexia.

Under-reporting of subjective symptoms and its prognostic value: a pooled analysis of 12 cancer clinical trials.

BACKGROUND: Oncologists tend to under-report subjective symptoms during cancer treatment. This study describes the under-reporting rate of selected symptoms and explores its association with overall survival (OS). A secondary aim is to test the association of patient-reported symptoms with OS. PATIENTS AND METHODS: This is a post hoc analysis on data pooled from 12 randomized trials, promoted by the National Cancer Institute of Naples (Italy), enrolling patients between 2002 and 2019, with published primary analyses. Occurrence and grade of six side-effects (anorexia, nausea, vomiting, constipation, diarrhea and fatigue) reported by physicians were compared with corresponding symptoms reported by patients in quality-of-life (QoL) questionnaires. Under-reporting was defined as the rate of cases reported grade 0 by the physician while grade ≥1 by the patient. Prognostic value was tested in a multivariable model stratified by trial, including age, sex and performance status as confounders. A landmark threshold was defined for OS analyses. RESULTS: 3792 patients with advanced lung, ovarian, pancreatic, breast or colorectal cancer were pooled; 2603 (68.6%) were eligible having at least one toxicity assessment and one QoL questionnaire, before the first planned disease restaging. Concordance between physicians' and patients' reporting was low with Cohen's k coefficients ranging from 0.03 (fatigue) to 0.33 (vomiting). Under-reporting ranged from 52.7% (nausea) to 80.5% (anorexia), and was not associated with OS. Patient-reported anorexia, vomiting and fatigue ('a little' or more) were significantly associated with shorter OS. CONCLUSIONS: Under-reporting of treatment side-effects is frequent, but it does not affect OS. Patients' reported symptoms should be used for prognostic evaluation.

From early relational experiences to non-suicidal self-injury in anorexia and bulimia nervosa: a structural equation model unraveling the role of impairments in interoception.

PURPOSE: Individuals with anorexia nervosa (AN) and bulimia nervosa (BN) frequently exhibit Non-Suicidal Self-Injury (NSSI), yet their co-occurrence is still unclear. To address this issue, the aim of this study was to elucidate the role of impairments in interoception in explaining the NSSI phenomenon in AN and BN, providing an explanatory model that considers distal (insecure attachment/IA and traumatic childhood experiences/TCEs) and proximal (dissociation and emotional dysregulation) risk factors for NSSI. METHOD: 130 patients with AN and BN were enrolled and administered self-report questionnaires to assess the intensity of NSSI behaviors, interoceptive deficits, IA, TCEs, emotional dysregulation and dissociative symptoms. RESULTS: Results from structural equation modeling revealed that impairments in interoception acted as crucial mediators between early negative relational experiences and factors that contribute to NSSI in AN and BN, particularly emotional dysregulation and dissociation. Precisely, both aspects of IA (anxiety and avoidance) and various forms of TCEs significantly exacerbated interoceptive deficits, which in turn are associated to the emergence of NSSI behaviors through the increase in levels of dissociation and emotional dysregulation. CONCLUSIONS: The proposed model provided a novel explanation of the occurrence of NSSIs in patients with AN and BN by accounting for the significance of interoception. LEVEL OF EVIDENCE: Level V-Cross-sectional observational study.

Adolescent activity-based anorexia has a substantial and prolonged impact on social behavior in young adult female rats.

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.

[The Second Web Questionnaire Survey on Cancer Cachexia Japanese Evidence for Patients Of Cancer Cachexiaâ ¡ (J-EPOCCâ ¡)-Challenges in Early Detection and Early Intervention for Appetite Loss and Weight Loss During Cancer Treatment].

In 2019, the Cancer Cachexia Web Questionnaire Survey(J-EPOCC), conducted among cancer patients, their families and healthcare professionals in Japan showed that nearly half of patients who had experienced appetite loss or weight loss during cancer treatment had not consulted with healthcare professionals about their symptoms, and it meant that patients missed the opportunity to receive medical intervention. Since anamorelin was approved in 2021 fo"r Cancer cachexia in non- small cell lung cancer, gastric cancer, pancreatic cancer and colorectal cancer", the treatment environment for cancer cachexia has greatly changed. Thus, the second Web Questionnaire Survey(J-EPOCCⅡ)was conducted in June 2022 to investigate changes in the problem awareness of cancer cachexia, especially appetite loss and weight loss, among patients and their family and healthcare professionals. The results showed that there was no apparent change in awareness of appetite loss and weight loss, suggesting many patients may miss treatment opportunities. Further disease awareness is required among patients and their families to enhance the understanding of the significance of therapeutic interventions for appetite loss or weight loss, and to call their attention for early detection and treatment.

Development of activity-based anorexia requires PKC-δ neurons in two central extended amygdala nuclei.

Anorexia nervosa (AN) is a serious psychiatric disease, but the neural mechanisms underlying its development are unclear. A subpopulation of amygdala neurons, marked by expression of protein kinase C-delta (PKC-δ), has previously been shown to regulate diverse anorexigenic signals. Here, we demonstrate that these neurons regulate development of activity-based anorexia (ABA), a common animal model for AN. PKC-δ neurons are located in two nuclei of the central extended amygdala (EAc): the central nucleus (CeA) and oval region of the bed nucleus of the stria terminalis (ovBNST). Simultaneous ablation of CeAPKC-δ and ovBNSTPKC-δ neurons prevents ABA, but ablating PKC-δ neurons in the CeA or ovBNST alone is not sufficient. Correspondingly, PKC-δ neurons in both nuclei show increased activity with ABA development. Our study shows how neurons in the amygdala regulate ABA by impacting both feeding and wheel activity behaviors and support a complex heterogeneous etiology of AN.