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.

Lipocalin 2 mediates appetite suppression during pancreatic cancer cachexia.

Lipocalin 2 (LCN2) was recently identified as an endogenous ligand of the type 4 melanocortin receptor (MC4R), a critical regulator of appetite. However, it remains unknown if this molecule influences appetite during cancer cachexia, a devastating clinical entity characterized by decreased nutrition and progressive wasting. We demonstrate that LCN2 is robustly upregulated in murine models of pancreatic cancer, its expression is associated with reduced food consumption, and Lcn2 deletion is protective from cachexia-anorexia. Consistent with LCN2's proposed MC4R-dependent role in cancer-induced anorexia, pharmacologic MC4R antagonism mitigates cachexia-anorexia, while restoration of Lcn2 expression in the bone marrow is sufficient in restoring the anorexia feature of cachexia. Finally, we observe that LCN2 levels correlate with fat and lean mass wasting and is associated with increased mortality in patients with pancreatic cancer. Taken together, these findings implicate LCN2 as a pathologic mediator of appetite suppression during pancreatic cancer cachexia.

Effects of Irregular Feeding on the Daily Fluctuations in mRNA Expression of the Neurosecretory Protein GL and Neurosecretory Protein GM Genes in the Mouse Hypothalamus.

Circadian desynchrony induced by a long period of irregular feeding leads to metabolic diseases, such as obesity and diabetes mellitus. The recently identified neurosecretory protein GL (NPGL) and neurosecretory protein GM (NPGM) are hypothalamic small proteins that stimulate food intake and fat accumulation in several animals. To clarify the mechanisms that evoke feeding behavior and induce energy metabolism at the appropriate times in accordance with a circadian rhythm, diurnal fluctuations in Npgl and Npgm mRNA expression were investigated in mice. Quantitative RT-PCR analysis revealed that the mRNAs of these two genes were highly expressed in the mediobasal hypothalamus during the active dark phase under ad libitum feeding. In mice restricted to 3 h of feeding during the inactive light phase, the Npgl mRNA level was augmented in the moment prior to the feeding period and the midnight peak of Npgm mRNA was attenuated. Moreover, the mRNA expression levels of clock genes, feeding regulatory neuropeptides, and lipid metabolic enzymes in the central and peripheral tissues were comparable to those of central Npgl and Npgm. These data suggest that Npgl and Npgm transcription fluctuates daily and likely mediates feeding behavior and/or energy metabolism at an appropriate time according to the meal timing.

Anorexic responses to trichothecene deoxynivalenol and its congeners correspond to secretion of tumor necrosis factor-α and interleukin-1ß.

Type B trichothecene mycotoxins comprise deoxynivalenol ("Vomitoxin", DON) and four structually related congeners: 15-acetyl- and 3-acetyl-deoxynivalenol (15-ADON and 3-ADON), nivalenol (NIV), 4-acetyl-nivalenol (fusarenon X, FX). These foodborne mycotoxins has been linked to food poisoning leading to anorexic response in human and several animal species. However, the pathophysiological basis for anorexic effect is relatively unclear. The goal of this research was to compare anorexic effect to type B trichothecenes and relate these effects to two common cytokines tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) following oral and IP exposure. Both cytokines were increased within 1-2 h in plasma and returned to basal concentrations at 6 h following exposure to DON and ADONs. FX evoked both cytokines with initial time and duration at 1-2 h and > 6 h, respectively. Elevation of TNF-α and IL-1ß induced by orally exposure to NIV did not occur until 2 h and recovered to basal concentrations at 6 h. Both cytokines were elevated at 1 h and lasted more than 6 h following IP exposure to NIV. Type B trichothecenes stimulated plasma secretion of both cytokines that were consistent with reduction of food intake. In conclusion, our findings demonstrate that TNF-α and IL-1ß act critical roles in type B trichothecenes-induced anorexic response.

Z-505, an Oral Ghrelin Receptor Agonist, Attenuates Anorexia After Total Gastrectomy in Rats.

BACKGROUND: Anorexia is a serious problem in patients with gastric cancer who have undergone gastrectomy. Ghrelin, an orexigenic hormone primarily secreted from the stomach, has been proposed to prevent anorexia. Significant reduction in plasma ghrelin levels after gastrectomy may contribute to lack of appetite and weight loss. In this study, we investigated the effects of Z-505, a ghrelin receptor agonist, on anorexia after total gastrectomy (TG) in a rat model. METHODS AND MATERIALS: Male Sprague-Dawley rats were used to establish a TG model, and then sham-operated (control) and TG rats were randomly assigned to four subgroups receiving administration of Z-505 (100 mg/kg, p.o., once daily) or vehicle for 14 d from day 14 to day 27 after TG. The food intake, body weight, and fat weight were evaluated during the test period. Moreover, the neuronal activity in the hypothalamus was evaluated on day 21 to investigate the mechanism of action of Z-505. RESULTS: In TG rats, Z-505 significantly improved the decrease in cumulative food intake induced by the surgery over 14 d (TG + vehicle; 213.8 ± 15.3 g, n = 12 versus TG + Z-505; 258.2 ± 13.1 g, n = 14, P < 0.05). Z-505 also significantly increased fat weight and had a milder effect on body weight over 14 d. In addition, Z-505 significantly increased the number of c-Fos-positive cells in the hypothalamic arcuate nucleus (TG + vehicle; 17.8 ± 2.0, n = 12 versus TG + Z-505; 72.2 ± 11.8, n = 12, P < 0.001). CONCLUSIONS: Z-505 may be a useful therapeutic treatment for anorexia after TG.

Adipokines and bone status in a cohort of anorexic patients.

INTRODUCTION: Bone loss in anorexia nervosa (AN) is multifactorial; its mechanisms are not yet clearly understood and may vary depending on disease duration and severity. To determine to what extent adipokines may be involved in the bone alterations found in anorexic patients, we evaluated plasma levels for leptin, adiponectin and Pref-1 against other clinical and biological parameters in a population of anorexic patients split according to weight and bone status. METHODS: Plasma concentrations of leptin, total adiponectin, high molecular weight (HMW) adiponectin, and Pref-1 were measured. The ratio of HMW adiponectin to total adiponectin - HMW (percentage) - was calculated. We divided our population into 5 groups with different phenotypes characterizing the severity of the disease and/or the severity of bone involvement: 1 - Normal BMD and body mass index (BMI): recovery from AN; 2 - Osteopenia (-217kg/m2; 3 - Osteopenia and BMI≤17kg/m2; 4 - Osteoporosis (Z-score≤-2) and BMI>17kg/m2; 5 - Osteoporosis and BMI≤17kg/m2. RESULTS: The study involved 80 anorexia nervosa patients. Mean BMI was 16.8±2.4kg/m2. No significant difference was found in total and HMW adiponectin plasma concentrations between the 5 groups. HMW (percentage) was significantly higher in group 5 compared to group 1. Leptin was significantly lower in groups 3 and 5 compared to the other groups. For the whole group femoral neck and hip BMD correlated negatively with total adiponectin and HMW adiponectin. No correlation was found between BMD (whatever the site) and plasma leptin. Multivariate analysis revealed that 2 factors - leptin and BMI - explained 10% of the variance in spine BMD. For femoral neck BMD, the 2 explanatory factors were BMI and total adiponectin which explained 14% of the variance in BMD. For total hip BMD, 27% of the variance in BMD was explained by 3 factors: leptin, BMI, and total adiponectin. CONCLUSION: Bone status in anorexia nervosa is mainly determined by BMI, leptin and adiponectin.

Role of neurotransmitters 5-hydroxytryptamine and substance P in anorexia induction following oral exposure to the trichothecene T-2 toxin.

Trichothecene mycotoxins, a family of common contaminants on cereal grains, are known to negatively impact human and animal health with adverse effect on food consumption being of particular concern. T-2 toxin has been previously demonstrated to induce anorectic response in several animal species including mouse, rat, rabbit. Although the T-2 toxin-induced anorectic response has been associated with the release of gut satiety hormone, much less is known about the role of neurotransmitter in this response. To address this gap, we employed a nocturnal mouse food refusal model to test the hypothesis that neurotransmitters 5-hydroxytryptamine (5-HT) and substance P (SP) mediate anorexia induction by T-2 toxin. Elevations of plasma 5-HT and SP markedly corresponded to anorexia induction following oral exposure to T-2 toxin. Direct administration of exogenous 5-HT and SP induced anorectic responses similar to T-2 toxin. The 5-HT3 receptor (5-HT3R) antagonist granisetron evoked a dose-dependent attenuation of both 5-HT- and T-2 toxin-induced anorectic responses. Pretreatment with neurokinin-1 receptor (NK-1R) antagonist Emend® dose-dependently attenuated both SP- and T-2 toxin-induced anorectic responses. To summarize, the results suggest that both 5-HT and SP play important roles in anorexia induction by T-2 toxin. 5-HT is more potent and long-acting than SP in this response.

Anorectic responses to T-2 toxin, HT-2 toxin, diacetoxyscirpenol and neosolaniol correspond to plasma elevations of neurotransmitters 5-hydroxytryptamine and substance P.

Trichothecene mycotoxins commonly contaminate cereal grains and are often linked to human and animal food poisoning. The rapid onset of anorexia is a common hallmark of trichothecenes-induced toxicity. Although the neurotransmitters 5-hydroxytryptamine (5-HT) and substance P (SP) are known to regulate appetite, it remains unknown whether these two neurotransmitters are involved in type A trichothecenes-induced anorectic response. The goal of this study is to relate plasma 5-HT and SP to anorectic responses induced by type A trichothecenes T-2 toxin (T-2), HT-2 toxin (HT-2), diacetoxyscirpenol (DAS) and neosolaniol (NEO). These four toxins evoked robust anorectic response and secretion of plasma 5-HT and SP at 1 mg/kg bw. Following oral exposure, plasma 5-HT and SP were elevated and all peaked at 2 h for T-2, HT-2, DAS and NEO. Following intraperitoneal (IP) administration, plasma 5-HT and SP were peaked at 6 h, 6 h, 2 h, 2 h and 2 h, 6 h, 2 h, 2 h for T-2, HT-2, DAS and NEO, respectively. Elevations of plasma 5-HT and SP markedly corresponded to anorexia induction by T-2, HT-2, DAS and NEO. Altogether, the results presented herein indicated that 5-HT and SP play contributory roles in anorectic responses induced by T-2, HT-2, DAS and NEO.

Characterization of low active ghrelin ratio in patients with advanced pancreatic cancer.

PURPOSE: Acyl ghrelin is an orexigenic peptide. Active ghrelin ratio, the ratio of acyl ghrelin to total ghrelin, has an important role in physiological functions and gastrointestinal symptoms. However, low active ghrelin ratio-related characteristics, gastrointestinal symptoms, and chemotherapy-induced gastrointestinal toxicity in patients with advanced pancreatic cancer have not been previously evaluated. The goal of this study was to identify low active ghrelin ratio-related factors in treatment-naïve advanced pancreatic cancer patients. METHODS: Patients with treatment-naïve advanced pancreatic cancer were eligible for inclusion in this study. Active ghrelin ratio and clinical parameters of patients were prospectively recorded. Factors correlated with low active ghrelin ratio and survival were analyzed. RESULTS: In total, 92 patients were analyzed. Low active ghrelin ratio-related factors were advanced age (P < 0.01), severe appetite loss (P < 0.01), and decreased cholinesterase (P < 0.01). The adverse events of grade 2 or higher anorexia tended to increase in patients with low active ghrelin ratio. However, no differences were found in survival and body composition between low and high active ghrelin ratio groups. CONCLUSIONS: Low active ghrelin ratio was related to lack of appetite and low cholinesterase and tended to be related to anorexia grade 2 or higher in patients with treatment-naïve advanced pancreatic cancer.

Anorectic response to the trichothecene T-2 toxin correspond to plasma elevations of the satiety hormone glucose-dependent insulinotropic polypeptide and peptide YY3-36.

T-2 toxin, a potent type A trichothecene mycotoxin, is produced by various Fusarium species and can negatively impact animal and human health. Although anorexia induction is a common hallmark of T-2 toxin-induced toxicity, the underlying mechanisms for this adverse effect are not fully understood. The goal of this study was to determine the roles of two gut satiety hormones, glucose-dependent insulinotropic polypeptide (GIP) and Peptide YY3-36 (PYY3-36) in anorexia induction by T-2 toxin. Elevations of plasma GIP and PYY3-36 markedly corresponded to anorexia induction following oral exposure to T-2 toxin using a nocturnal mouse anorexia model. Direct administration of exogenous GIP and PYY3-36 similarly induced anorectic responses. Furthermore, the GIP receptor antagonist Pro3GIP dose-dependently attenuated both GIP- and T-2 toxin-induced anorectic responses. Pretreatment with NPY2 receptor antagonist JNJ-31020028 induced a dose-dependent attenuation of both PYY3-36- and T-2 toxin-induced anorectic responses. To summarize, these findings suggest that both GIP and PYY3-36 might be critical mediators of anorexia induction by T-2 toxin.

The role of IL-6 in exercise-induced anorexia in normal-weight boys.

Our previous study showed that interleukin-6 (IL-6) is associated with suppression of appetite after high-intensity exercise (HIEX), but an independent role in food intake (FI) was not defined. We hypothesized that IL-6 suppresses appetite and FI, independently of appetite hormones, after HIEX in normal-weight (NW) boys. We investigated the effect of HIEX, with and without the inflammation inhibitor ibuprofen (IBU), on IL-6, other biomarkers of inflammation and appetite, FI, and ratings of appetite in NW boys. Fifteen NW boys (aged 13-18 years) were randomly assigned in a crossover design to 4 sessions: (i) water and rest, (ii) IBU and rest, (iii) water and HIEX, and (iv) IBU and HIEX. HIEX consisted of three 10-min bouts of exercise at 75% of maximal oxygen uptake with 90 s of active rest between bouts. IBU (300 mg) was given as a liquid suspension. FI, ratings of appetite, and plasma biomarkers of appetite, inflammation, stress, and glucose control were measured. FI was not affected by HIEX or IBU. Appetite increased over time (p = 0.002) but was lower after HIEX (p < 0.001) and not affected by IBU. HIEX, but not IBU, resulted in higher levels of IL-6 (p < 0.001) and cortisol (p < 0.001) and lower active ghrelin (p < 0.001). IL-6 correlated with active ghrelin (r = 0.37; p = 0.036) and cortisol (r = 0.26; p = 0.049). An independent role for IL-6 in appetite suppression was not supported. However, IL-6 was correlated with active ghrelin and cortisol, thus potentially mediating appetite via these interactions.

Potential roles for glucagon-like peptide-17-36 amide and cholecystokinin in anorectic response to the trichothecene mycotoxin T-2 toxin.

Anorexia is a hallmark of animal and human exposed to T-2 toxin, a most poisonous trichothecene mycotoxins contaminating various cereal grains including wheat, corn and barley. Although this adverse effect has been well characterized in several animal species, the underlying mechanisms are unclear. The goal for this study was to elucidate the roles of two gut satiety hormones, glucagon-like peptide-17-36 amide (GLP-1) and cholecystokinin (CCK) in T-2 toxin-evoked anorectic response using a mouse anorexia bioassay. Elevations of plasma GLP-1 and CCK significantly corresponded to anorexia induction by T-2 toxin. Direct administration of exogenous GLP-1 and CCK markedly evoked anorectic responses similar to T-2 toxin. The GLP-1 receptor (GLP-1R) antagonist Exendin9-39 dose-dependently cause attenuation of both GLP-1- and T-2 toxin-induced anorectic responses. Pretreatment with the CCK1 receptor (CCK1R) antagonist SR 27897 and CCK2 receptor (CCK2R) antagonist L-365,260 attenuated anorexia induction by both CCK- and T-2 toxin in a dose dependent manner. Taken together, our findings suggest that both GLP-1 and CCK play contributory roles in T-2 toxin-induced anorexia.

Protective Effect of D-Methionine on Body Weight Loss, Anorexia, and Nephrotoxicity in Cisplatin-Induced Chronic Toxicity in Rats.

D-methionine is a sulfur-containing amino acid that can act as a potent antioxidant. Anorexia and nephrotoxicity are side effects of cisplatin. The protective effects of D-methionine on cisplatin-induced anorexia and renal injury were investigated. The model of chronic cisplatin administration (5 mg/kg body weight) involved intraperitoneal injection on days 1, 8, and 15 and oral D-methionine (300 mg/kg body weight) coadministration daily for 20 days. On the 21st day of treatment, food intake and body weight in the cisplatin-treated group significantly decreased by 52% and 31%, respectively, when compared with a control group. D-methionine coadministration with cisplatin decreased food intake and body weight by 29% and 8%, respectively. In cisplatin-treated rats, white blood cell, mean corpuscular volume, and platelet values significantly decreased, while mean corpuscular hemoglobin concentration significantly increased by 8.6% when compared with control rats. Cisplatin administration resulted in significantly decreased feeding efficiency, elevated renal oxidative stress, and reduced antioxidative activity. Leukocyte infiltration, tubule vacuolization, tubular expansion, and swelling were observed in the kidneys of cisplatin-treated rats. Oral D-methionine exhibited an antianorexic effect, with improvement in food intake, feeding efficiency, and hematological toxicities, as well as a protective effect against nephrotoxicity by elevated antioxidative activity. D-methionine may serve as a chemoprotectant in patients receiving cisplatin as part of a chemotherapy regimen.

Age modifies the association between serum obestatin, appetite and nutritional status in maintenance hemodialysis patients.

BACKGROUND/OBJECTIVES: Increased age is strongly associated with anorexia and protein-energy wasting (PEW) in maintenance hemodialysis (MHD) population. We hypothesized that the association of obestatin, a recently discovered anorexigenic gut hormone, with appetite and nutritional status differs by age groups. SUBJECTS/METHODS: We performed a cross-sectional study on 261MHD patients. Obestatin, acyl-ghrelin, markers of inflammation (CRP, IL-6, TNF-α) and nutrition (self-reported appetite, dietary intake, biochemical nutritional parameters, and body composition) were measured. RESULTS: Obestatin was associated with appetite in multivariate analyses even after controlling for such confounders as lean body mass (LBM), IL-6 and acyl-ghrelin in patients younger than 71 years. For each ng/ml increase in obestatin levels, the odds for diminished appetite was 0.75 (95% CI: 0.59-0.96). However, these associations were not observed in patients 71 years and older. Multivariable logistic regression models (including appetite) also showed increasing odds for PEW (defined by ESPEN consensus-based criteria for the diagnosis of malnutrition) across increasing serum obestatin levels (OR: 1.51, 95% CI: 1.05-2.18) in patients 71 years and older. However, after lean body mass (LBM) was added to this model, the association between obestatin and malnutrition was abolished (OR: 1.26, 95% CI: 0.83-1.91). CONCLUSIONS: The association between serum obestatin, appetite and PEW differs depending on age in MHD patients. A positive link with appetite exists in patients younger than 71 years, whereas this relationship disappears by the age of 71. In older MHD patients, obestatin is associated with PEW through mechanisms related to LBM, but not to appetite.

Efficacy of aprepitant for CHOP chemotherapy-induced nausea, vomiting, and anorexia.

The objective of this study was to evaluate whether aprepitant in addition to 5-HT3 receptor antagonist is useful for preventing chemotherapy-induced nausea and vomiting (CINV) and anorexia in patients receiving CHOP therapy, and to evaluate the relationship between in vivo kinetics of plasma substance P and these adverse events. Patients with malignant lymphoma who received CHOP chemotherapy or THP (THP-ADR)-COP therapy were investigated for CINV and anorexia for 5 days after the start of chemotherapy. With the first course of chemotherapy, all patients received only granisetron on day1 as an antiemetic. Patients who experienced nausea, vomiting, or anorexia exceeding grade 1 in the first course received aprepitant for 3 days in addition to granisetron with the second course of CHOP chemotherapy. Plasma substance P concentrations at 24 and 72 hours after chemotherapy were measured. Nineteen patients were evaluated. Nausea, vomiting, or anorexia was observed with the first course in 7 of 19 patients. During the second course with aprepitant, no patients experienced vomiting, and the toxicity grade of nausea, vomiting, or anorexia was decreased compared with those in the first course. Substance P concentrations showed no differences after chemotherapy, in patients with nausea, vomiting, or anorexia and in patients without. The addition of aprepitant to 5-HT3 receptor antagonist appears effective for CINV or anorexia for patients who received CHOP chemotherapy.

Gut satiety hormones cholecystokinin and glucagon-like Peptide-17-36 amide mediate anorexia induction by trichothecenes T-2 toxin, HT-2 toxin, diacetoxyscirpenol and neosolaniol.

The food-borne trichothecene mycotoxins have been documented to cause human and animal food poisoning. Anorexia is a hallmark of the trichothecene mycotoxins-induced adverse effects. Type B trichothecenes have been previously demonstrated to elicit robust anorectic responses, and this response has been directly linked to secretion of the gut satiety hormones cholecystokinin (CCK) and glucagon-like peptide-17-36 amide (GLP-1). However, less is known about the anorectic effects and underlying mechanisms of the type A trichothecenes, including T-2 toxin (T-2), HT-2 toxin (HT-2), diacetoxyscirpenol (DAS), neosolaniol (NEO). The purpose of this study was to relate type A trichothecenes T-2, HT-2, DAS and NEO-induced anorectic response to changes plasma concentrations of CCK and GLP-1. Following both oral gavage and intraperitoneal (IP) administration of 1mg/kg bw T-2, HT-2, DAS and NEO evoked robust anorectic response and secretion of CCK and GLP-1. Elevations of plasma CCK markedly corresponded to anorexia induction by T-2, HT-2, DAS and NEO. Following oral exposure, plasma CCK was peaked at 6h, 6h, 2h, 2h and lasted up to 24h, 24h, > 6h, > 6h for T-2, HT-2, DAS and NEO, respectively. IP exposed to four toxins all induced elevation of CCK with peak point and duration at 6h and >24h, respectively. In contrast to CCK, GLP-1 was moderately elevated by these toxins. Following both oral and IP exposure, T-2 and HT-2 evoked plasma GLP-1 elevation with peak point and duration at 2h and 6h, respectively. Plasma GLP-1 was peaked at 2h and still increased at 6h for IP and oral administration with DAS and NEO, respectively. In conclusion, CCK plays a contributory role in anorexia induction but GLP-1 might play a lesser role in this response.

Hypothalamic pathways regulate the anorectic action of p-chloro-diphenyl diselenide in rats.

Behavioral studies have suggested that (p-ClPhSe)2 elicits an anorectic-like action in rats by inducing multiple effects such as satiety-enhancing effect, malaise and specific flavor; however, the molecular mechanisms underlying its anorexigenic action remain unclarified. Here, male Sprague-Dawley rats received acute and sub-chronic intraperitoneal treatments with (p-ClPhSe)2; thereafter, in vivo and ex vivo analyses were carried out. The present study reveals that the reduction of food intake resulting from a single treatment with (p-ClPhSe)2 (1mg/kg, i.p.) was associated with decreased hypothalamic levels of pro-melanin-concentrating hormone (pro-MCH) and orexin precursor. In addition, repeated administrations of (p-ClPhSe)2 (10mg/kg; i.p.) for 7 days induced sustained food intake suppression, body weight loss and white fat reduction. Measurements of brown adipose tissue content and temperature as well as data obtained from a pair-fed group indicated that the effects of (p-ClPhSe)2 on the body weight are closely related to its anorexigenic actions, ruling out the possibility of increased thermogenesis. Furthermore, (p-ClPhSe)2 reduced the hypothalamic orexin precursor levels when repeatedly administered to rats. Sub-chronic treatment with (p-ClPhSe)2 caused a decrease of serum triglyceride levels and down-regulation of hepatic cholesterol content. Therefore, the current study characterized the anorectic and reducing body weight actions of (p-ClPhSe)2 in Sprague-Dawley rats. Besides, the set of results suggests that food intake suppressant effects triggered after (p-ClPhSe)2 administration to rats are mainly related with the lower orexin levels in hypothalamus after acute and sub-chronic treatments.