Increased Food Intake Research Articles

Combination therapy of corylifol A and anamorelin attenuates cachexia by decreasing pro-inflammatory cytokines, inhibiting lipolysis and increasing food intake in a murine colon cancer model

PurposeIn our previous study, we found that corylifol A (CYA), an active component derived from Psoralea corylifolia L, exhibited ameliorating effects on cancer cachexia. Anamorelin (AML), a ghrelin receptor agonist, is the only approved drug for the clinical treatment of cancer cachexia. Here, we checked the combination of CYA and AML on muscle atrophy and fat lipolysis in cancer cachexia mice to explore the possible clinic therapeutic potency of the combination on cancer cachexia.MethodsC26 colon tumor-bearing mice, a well-established animal model of cancer cachexia, were used to evaluate the effects of combined therapy involving CYA and AML on cancer cachexia and compared with those of CYA or AML alone. Histological analysis was performed to assess the changes in gastrocnemius (GAS) muscle tissue and epididymal adipose tissue (eWAT) and the possible involved molecular pathways were explored using western blotting and ELISA.ResultsTreatments of CYA, AML, or CYA+AML all significantly ameliorated the body weight decrease, muscle atrophy as well as fat loss in the tumor-bearing mice. Notably, the ameliorating effects of CYA+AML on fat loss were more significant than CYA or AML alone. The eWAT weight of mice in healthy control, C26 model, C26 +CYA, C26 +AML or C26 +CYA +AML group was 0.48 ± 0.07, 0.21 ± 0.10, 0.26 ± 0.10, 0.37 ± 0.10 and 0.48 ± 0.18 g, respectively. CYA+AML could increase food intake, significantly decrease the serum levels of inflammatory cytokines (TNF-α and IL-6) and inhibit the activation (phosphorylation) of hormone-sensitive lipase (HSL) in the eWAT tissues of the C26 tumor-bearing mice. Treatment of CYA along could significantly decrease the serum TNF-α level of the C26 tumor-bearing mice. Treatment of AML alone could increase food intake but could not decrease the serum levels of inflammatory cytokines of the C26 tumor-bearing mice.ConclusionThese results suggested that the effects of CYA+AML include both the appetite-stimulating effects of AML and the anti-inflammatory effects of CYA. CYA+AML was better than CYA or AML alone in ameliorating cancer cachexia, especially fat loss, of C26 tumor-bearing mice and might be a novel and beneficial therapeutic option for cancer cachexia.

Water-soluble garlic polysaccharide (WSGP) improves ulcerative colitis by modulating the intestinal barrier and intestinal flora metabolites

WSGP has demonstrated significant potential for various bioactive effects. However, limited research has explored their anti-ulcerative colitis (UC) effects and mechanism on the colonic system and gut microbial metabolites. We evaluated the ameliorative effects of WSGP on the UC mice model. Using H&E to assess histological injury of colon morphology, AB-PAS staining to detect mucin secretion from goblet cells and the mucous layer, IF to evaluate the expression of intercellular tight junction proteins, ELISA to measure inflammatory factors, WB analysis to measure protein expression of inflammatory signaling pathways, RT-qPCR to quantify gene transcription of inflammatory factors, and LC-MS to analyze metabolites in mouse cecum contents. WSGP supplementation increased food intake, body weight, and colon length while reducing disease activity and histological scores in colitis-afflicted mice. WSGP mitigated colonic tissue damage and restored intestinal barrier integrity by suppressing NF-κB/STAT3 signaling, thereby decreasing gene transcription, protein expression of proinflammatory factors, and nitric oxide production. Additionally, WSGP improved UC by altering the variety of intestinal microbial metabolites. This study demonstrates that WSGP supplementation attenuates UC mice by suppressing the NF-κB/STAT3 signaling pathway, enhancing mucosal barrier function, reducing pro-inflammatory cytokines, and modulating gut microbial metabolites.

A role for the circadian photoreceptor CRYPTOCHROME in regulating triglyceride metabolism in Drosophila.

The biological rhythms generated by the endogenous circadian clocks across the tree of life regulate numerous behavioural, metabolic and physiological processes. Although evidence from various studies in Drosophila melanogaster indicates the importance of the core circadian clock genes in the intricate interplay between the circadian clock and metabolism, little is known about the contribution of the circadian photoreceptor/s in this process. The deep brain circadian photoreceptor CRYPTOCHROME (CRY) is essential for resetting the clock in response to light and is also highly expressed in metabolically active tissues in Drosophila. In this study, we sought to explore the possible roles played by CRY in triglyceride metabolism. We observed that the cry mutant (cry01) flies exhibited increased starvation resistance and triglyceride levels under both 12-hour (h) light:12 h dark cycle (LD) and under constant light (LL) compared to the control w1118 flies. We also observed that cry01 flies had significantly increased food intake, glycogen concentrations and life span under LD. In addition, cryptochrome seemed to affect triglyceride levels in adult flies in response to calorie-restricted and high-fat diets. These results suggest a role for the circadian photoreceptor CRY in triglyceride metabolism in Drosophila.

A secondary β-hydroxybutyrate metabolic pathway linked to energy balance.

β-hydroxybutyrate (BHB) is an abundant ketone body. To date, all known pathways of BHB metabolism involve interconversion of BHB and primary energy intermediates. Here we show that CNDP2 controls a previously undescribed secondary BHB metabolic pathway via enzymatic conjugation of BHB and free amino acids. This BHB-ylation reaction produces a family of endogenous ketone metabolites, the BHB-amino acids. Genetic ablation of CNDP2 in mice eliminates tissue amino acid BHB-ylation activity and reduces BHB-amino acid levels. Administration of BHB-Phe, the most abundant BHB-amino acid, to obese mice activates neural populations in the hypothalamus and brainstem and suppresses feeding and body weight. Conversely, CNDP2-KO mice exhibit increased food intake and body weight upon ketosis stimuli. CNDP2-dependent amino acid BHB-ylation and BHB-amino acid metabolites are also conserved in humans. Therefore, the metabolic pathways of BHB extend beyond primary metabolism and include secondary ketone metabolites linked to energy balance.

Maternal perceived stress, household disorder, eating behaviors and adiposity of women and their children

BackgroundStress is associated with physiological and behavioral adaptations that increase the risk for obesity and related diseases in adults and children. Mechanisms linking stress to chronic disease are diverse and not fully elucidated, but research suggests stress may impact eating behaviors and increase food intake and thereby, risk for obesity. ObjectiveThe purpose of this study was to test the hypotheses that women's perceived stress and household disorder are associated with more uncontrolled and emotional eating among women, more food responsiveness and emotional overeating among their children, and greater adiposity in both women and their children. MethodsWomen (n = 86) completed the Perceived Stress Scale, Confusion, Hubbub and Order Scale, Three Factor Eating Questionnaire, and Child Eating Behavior Questionnaire. Total body fat (%) was measured via dual-energy X-ray absorptiometry. Linear regression models evaluated associations of perceived stress and household disorder with eating behaviors and adiposity of women and their children (4–10 years old). ResultsIn a sample of predominantly non-Hispanic Black women (84.9%, n = 73), more perceived stress and household disorder were associated with more uncontrolled and emotional eating (p < 0.05). Women's perceived stress was not associated with their children's eating behaviors; however, household disorder was positively associated with children's food responsiveness and emotional overeating (p < 0.05). Perceived stress and household disorder were not associated with adiposity of women or their children. ConclusionsThese findings suggest household disorder may be a factor for home-based interventions to consider when addressing eating behaviors among families with children.

Association between Weight Gain and Sex-Related Differences through 5-Fluorouracil Administration.

Research on sex differences has increased across various fields, including cancer and its treatment domains. Reports have indicated sex differences in cancer incidence, survival rates, and the efficacy of anticancer drugs. However, such reports are limited, and in-depth assessments of the underlying mechanisms are still in progress. Although various chemotherapeutic regimens are applicable for breast cancer treatment, reports have surfaced regarding weight gain in female patients undergoing fluorouracil, epirubicin, cyclophosphamide (FEC) or cyclophosphamide, methotrexate, fluorouracil (CMF) therapy. We hypothesized the potential of 5-fluorouracil (5-FU) in weight gain and sex-related differences. To address this, we conducted experiments in mice to confirm weight gain and sex differences following 5-FU administration, and elucidate the underlying mechanisms. Our findings revealed weight gain and increased food intake in female mice following 5-FU administration. Additionally, female mice receiving 5-FU exhibited increased norepinephrine and α1- and α2-adrenergic receptor expression, reduced estradiol levels, and increased ghrelin levels. These results indicate 5-FU administration-induced sex differences in weight gain and implicate increased food intake because of increased norepinephrine and α1- and α2-adrenergic receptor expression, reduced estradiol levels, and a subsequent increase in ghrelin levels, which contribute to weight gain in female patients undergoing CMF therapy.

Long-term Metabolic Dysfunction Programming in Female Mice by Serial Moderate Restriction of a High-fat High-sucrose Diet.

While intermittent fasting leads to weight loss and improved glucose metabolism, food insecurity, the insufficient access to food for a healthy life, is associated with obesity and adverse cardiometabolic health, especially in women. We aimed to characterize the effects of intermittently restricted feeding on energy balance and glucose tolerance in female mice. Female C57BL/6J mice were fed a high-fat, high-sucrose diet and intermittently food restricted to 60% of control littermates' ad libitum intake, starting at weaning and until week 19. Restricted mice were subsequently allowed ad libitum access to the same diet. Body composition and energy balance were measured at weeks 18.5, 19, 30, and 40. At week 42, mice underwent an intraperitoneal glucose tolerance test and plasma appetitive hormones measurements after nutrient gavage. During the food restriction phase, restricted mice accrued lower weight and fat mass than controls despite periodic ad libitum food access. Reintroduction of continuous ad libitum food caused increased food intake during the light phase and increased body mass in restricted mice. Minor differences in body composition-adjusted energy expenditure between groups were observed at week 40. At week 42, glucose tolerance was impaired in restricted mice compared to controls, and trends toward lower levels of postprandial anorexigenic hormones glucagon-like peptide-1 and pancreatic polypeptide were observed. Our findings suggest that repeated intermittent food restriction leads to changes in eating behavior that predispose to glucose intolerance when food is freely available. Future studies are needed to elucidate the specific mechanisms underlying these changes.

Negative feedback control of hypothalamic feeding circuits by the taste of food

The rewarding taste of food is critical for motivating animals to eat, but whether taste has a parallel function in promoting meal termination is not well understood. Here, we show that hunger-promoting agouti-related peptide (AgRP) neurons are rapidly inhibited during each bout of ingestion by a signal linked to the taste of food. Blocking these transient dips in activity via closed-loop optogenetic stimulation increases food intake by selectively delaying the onset of satiety. We show that upstream leptin-receptor-expressing neurons in the dorsomedial hypothalamus (DMHLepR) are tuned to respond to sweet or fatty tastes and exhibit time-locked activation during feeding that is the mirror image of downstream AgRP cells. These findings reveal an unexpected role for taste in the negative feedback control of ingestion. They also reveal a mechanism by which AgRP neurons, which are the primary cells that drive hunger, are able to influence the moment-by-moment dynamics of food consumption.

Effects of Repeated Administration of Rauwolfia Serpentina on Stress-Induced Anorexia and Leptin Levels: Relationship With Adaptation to Stress

Background: Stress is a major contributor to various health issues, including depression, anorexia nervosa, diabetes, and obesity. Rauwolfia serpentina, a traditional medicinal plant, has shown potential in alleviating stress-induced effects due to its influence on serotonin neurotransmission and its anxiolytic properties. Objective: This study aimed to investigate the effects of repeated administration of Rauwolfia serpentina on stress-induced anorexia and leptin levels, and its relationship with adaptation to stress in rats. Methods: Male albino Wistar rats were divided into four groups: DMSO unstressed, DMSO stressed, Rauwolfia serpentina unstressed, and Rauwolfia serpentina stressed. The stressed groups were subjected to two hours of immobilization daily for five days, followed by oral administration of Rauwolfia serpentina at 10 mg/kg. Behavioral assessments included the open field and light-dark transition tests. Body weight, food intake, and plasma levels of glucose, leptin, and corticosterone were measured. Data were analyzed using ANOVA with post-hoc Newman-Keuls test, and significance was set at p&lt;0.05. Results: Rauwolfia serpentina significantly improved body weight maintenance (98.9 ± 1.3% vs. 99.5 ± 1.7%) and increased food intake (16.3 ± 0.6 g vs. 16.5 ± 0.5 g) in stressed rats. It also reduced anxiety-like behaviors and lowered corticosterone levels (15.9 ± 1.6 ng/mL vs. 18.4 ± 1.7 ng/mL) in stressed groups (p&lt;0.05). Conclusion: Rauwolfia serpentina effectively alleviates stress-induced anorexigenic and anxiogenic effects, suggesting its potential as a therapeutic agent for managing stress-related disorders.

Efficacy of cordycepin against Neospora caninum infection in vitro and in vivo

Neospora caninum (N. caninum) is an obligate intracellular Apicomplexa parasite that causes abortions in dairy cows and incurs substantial to significant economic losses in the global dairy farming industry. Cordycepin, a nucleoside antibiotic derived from Chinese medicine Cordyceps militaries, exhibits diverse biological activities. However, it remains unclear whether cordycepin possesses inhibitory effects against N. caninum infection. Therefore, this study aimed to establish both in vivo and in vitro models of N. caninum to investigate the potential impact of cordycepin against N. caninum infection. We successfully established an in vitro model of N. caninum infection in RAW264.7 cells, followed by qRT- PCR analysis to detect the content of N. caninum DNA within the cells. The effects of cordycepin on N. caninum was observed using the Giemsa method on RAW264.7, and the rate of cell infection was calculated. Cordycepin exhibited inhibitory effects on N. caninum tachyzoites in vitro, preserving cellular integrity and reducing the rate of cell infection. In mice, we established an in vivo model of N. caninum infection and detected N. caninum presence in tissues using. Real-time fluorescence quantitative PCR. Histopathological changes were observed through Hematoxylin-eosin staining. Liver function was assessed by using glutamic acid aminotransferase (ALT) and aspartic acid aminotransferase (AST) kits. Oxidative stress status was measured using catalase (CAT), malondialdehyde (MDA), and glutathione (GSH) kits. Compared with the model group, mice treated with cordycepin showed reduced clinical symptoms, increased food intake, and their body weight (P=0.0143, P=0.0068) was significantly higher than those in the model group. Furthermore, cordycepin treatment significantly alleviated hepatic cord disorders, hepatocellular swelling, detachment, and vacuolization; duodenal epithelial detachment and shortening of villi caused by N. caninum infection. Cordycepin administration reduced the increase in ALT (P=0.01, P=0.008) and AST (P<0.001) levels caused by N. caninum infection, while ameliorating hepatocyte swelling, necrosis, and detachment as well as inflammatory cell infiltration within mice liver; it also led to shortened or even disappeared duodenal villi along with and oedema of the submucosa. Analysis of oxidative stress showed that cordycepin ameliorated the damage caused by N. caninum by reducing MDA (P=0.03, P=0.02, P=0.005) and increasing CAT (P=0.004, P<0.001) and GSH (P=0.004, P<0.001) levels. In conclusion, this study reports for the first time on cordycepin's efficacy against N. caninum infection providing a potential candidate drug for neosporosis treatment.

Lactating striped hamsters (Cricetulus barabensis) do not decrease the thermogenic capacity to cope with extreme cold temperature

For small non-hibernating mammals, a high thermogenic capacity is important to increase activity levels in the cold. It has been previously reported that lactating females decrease their thermogenic activity of brown adipose tissue (BAT), whereas their capacity to cope with extreme cold remains uncertain. In this study we examined food intake, body temperature and locomotor behavior, resting metabolic rate, non-shivering thermogenesis, and cytochrome c oxidase activity, and the rate of state 4 respiration of liver, skeletal muscle, and BAT in striped hamsters (Cricetulus barabensis) at peak lactation and non- breeding hamsters (controls). The lactating hamsters and non- breeding controls were acutely exposed to −15°C, and several markers indicative of thermogenic capacity were examined. In comparison to non-breeding females, lactating hamsters significantly increased food intake and body temperature, but decreased locomotor behavior, and the BAT mass, indicative of decreased BAT thermogenesis at peak lactation. Unexpectedly, lactating hamsters showed similar body temperature, resting metabolic rate, non-shivering thermogenesis with non-breeding females after acute exposure to −15°C. Furthermore, cytochrome c oxidase activity of liver, skeletal muscle and BAT, and serum thyroid hormone concentration, and BAT uncoupling protein 1 expression, in lactating hamsters were similar with that in non-breeding hamsters after acute extreme cold exposure. This suggests that lactating females have the same thermogenic capacity to survive cold temperatures compared to non-breeding animals. This is particularly important for females in the field to cope with cold environments during the period of reproduction. Our findings indicate that the females during lactation, one of the highest energy requirement periods, do not impair their thermogenic capacity in response to acute cold exposure.

Evaluation of the cognitive, physiological, and biomarker effects of heavy metal exposure in Wistar rats.

Individuals exposed to heavy metals are known to experience physiological and biochemical changes, which raise questions regarding possible health effects. In our earlier research, significant concentrations of vanadium (V), mercury (Hg), cadmium (Cd), and arsenic (As) were found in food and medical packaging materials. This study aimed to evaluate the cognitive, physiological, and biomarker effects of select heavy metal exposure in Wistar rats. Over a 13-week period, five groups of rats (six rats per group, with both males and females) were assessed to study the effects of oral exposure to V, Hg, Cd, and As. The study focused on evaluating physiological, cognitive, and biochemical markers, with the results compared to those of a control group. Comparing all groups of rats treated with heavy metals, the study revealed significant deficits in learning and spatial orientation (water maze test); rats treated with V, Cd, and Hg showed signs of depression. Rats treated with As also showed signs of hyperactivity, which may indicate a connection to attention-deficit hyperactivity disorder (rat tail suspension test). The groups exposed to different heavy metals varied in their physiological (water and food intake, urine and feces output) and biochemical responses (enzyme-linked immunosorbent assay, prostate-specific antigen, T3, T4, thyroid-stimulating hormone, carcinoembryonic antigen, and blood glucose analysis), with Hg exhibiting the strongest impacts. Rats given Hg showed signs of hypothyroidism, such as increased food intake and weight gain. This study clarifies the complex relationships between exposure to heavy metals and various biological systems, shedding light on their potential health impacts. The findings provide insight into the effects of heavy metals on neural and thyroid tissues, as well as their propensity to cause cellular dedifferentiation. However, the study has certain limitations, such as the relatively short duration of exposure and the use of only a few selected biomarkers. Future research should focus on long-term exposure studies, incorporate a broader range of biomarkers, and explore the underlying mechanisms at a molecular level to better understand the full spectrum of health risks associated with heavy metal exposure.

Effect of Photoperiod and Illuminance on Daily Activity Patterns, Physiology, and NPY Peptide Expression in Migratory Redheaded Buntings (Emberiza bruniceps)

Introduction: Light is the primary source of energy and regulates seasonal changes in physiology and behavior. The role of photoperiod has been much investigated in several bird species, but the role of illumination in seasonal adaptations of passerine finches is less understood. We, therefore, investigated the effects of photoperiod and illuminance on migratory physiology in a Palearctic-Indian migratory finch, redheaded bunting (Emberiza bruncieps). Methods: Photosensitive buntings maintained under short days (8L:16D) were divided into three groups receiving 5, 25, and 100 lux of white daytime illuminance, respectively. Thereafter, using photoperiodic manipulation three life history states, i.e., nonmigratory (NM), premigratory (PM), and migratory (MIG) states were induced in the buntings. The birds in the MIG state were consecutively perfused after seven nights of Zugunruhe (nighttime migratory restlessness) for neuropeptide Y (NPY)-immunohistochemistry, which is involved in a wide range of functions including energy homeostasis, vision, and fat deposition in birds. Results: We found differential effects of illuminance on locomotor activity and physiology. Photostimulated birds showed intense nighttime activity in the MIG state. We observed premigratory hyperphagia in the birds, with increased food intake in the 100 lux group, which was reflected in the body mass gain in the MIG state. NPY expression on the periphery of the nucleus rotundus suggests its potential role in visual acuity, where the NPY-cell count significantly decreased under 25 lux illumination. Conclusion: We demonstrate that migrating birds may also experience physiological effects from changes in daytime illumination. We observed illuminance-dependent variations in the quantity of food consumed by the birds. It indicates that the illuminance may also impact the encephalic centers that control food intake.

Activation of α7 nicotinic receptors attenuated hyperalgesia and anxiety induced by palatable obesogenic diet withdrawal

Consumption of palatable food (PF) can alleviate anxiety, and pain in humans. Contrary, spontaneous withdrawal of long-term PF intake produces anxiogenic-like behavior and abnormal pain sensation, causing challenges to weight-loss diet and anti-obesity agents. Thus, we examined α7-nicotinic acetylcholine receptors (α7nAChR) involvement since it plays essential role in nociception and psychological behaviors. MethodsAdult male C57BL/6 mice were placed on a Standard Chow (SC) alone or with PF on intermittent or continuous regimen for 6 weeks. Then, mice were replaced with normal SC (spontaneous withdrawal). Body weight, food intake, and calories intake with and without the obesogenic diet were measured throughout the study. During PF withdrawal, anxiety-like behaviors and pain sensitivity were measured with PNU-282987 (α7nAChR agonist) administration. ResultsSix weeks of SC + PF-intermittent and continuous paradigms produced a significant weight gain. PF withdrawal displayed hyperalgesia and anxiety-like behaviors. During withdrawal, PNU-282987 significantly attenuated hyperalgesia and anxiety-like behaviors. ConclusionThe present study shows that a PF can increase food intake and body weight. Also, enhanced pain sensitivity and anxiety-like behavior were observed during PF withdrawal. α7nAChR activation attenuated anxiolytic-like behavior and hyperalgesia in PF abstinent mice. These data suggest potential therapeutic effects of targeting α7 nAChRs for obesity-withdrawal symptoms in obese subjects.

Tanycytic transcytosis inhibition disrupts energy balance, glucose homeostasis and cognitive function in male mice

ObjectivesIn Western society, high-caloric diets rich in fats and sugars have fueled the obesity epidemic and its related disorders. Disruption of the body-brain communication, crucial for maintaining glucose and energy homeostasis, arises from both obesogenic and genetic factors, leading to metabolic disorders. Here, we investigate the role of hypothalamic tanycyte shuttles between the pituitary portal blood and the third ventricle cerebrospinal fluid in regulating energy balance. MethodsWe inhibited vesicle-associated membrane proteins (VAMP1-3)-mediated release in tanycytes by expressing the botulinum neurotoxin type B light chain (BoNT/B) in a Cre-dependent manner in tanycytes. This was achieved by injecting either TAT-Cre in the third ventricle or an AAV1/2 expressing Cre under the control of the tanycyte-specific promoter iodothyronine deiodinase 2 into the lateral ventricle of adult male mice. ResultsIn male mice fed a standard diet, targeted expression of BoNT/B in adult tanycytes blocks leptin transport into the mediobasal hypothalamus and results in normal-weight central obesity, including increased food intake, abdominal fat deposition, and elevated leptin levels but no marked change in body weight. Furthermore, BoNT/B expression in adult tanycytes promotes fatty acid storage, leading to glucose intolerance and insulin resistance. Notably, these metabolic disturbances occur despite a compensatory increase in insulin secretion, observed both in response to exogenous glucose boluses in vivo and in isolated pancreatic islets. Intriguingly, these metabolic alterations are associated with impaired spatial memory in BoNT/B-expressing mice. ConclusionsThese findings underscore the central role of tanycytes in brain-periphery communication and highlight their potential implication in the age-related development of type 2 diabetes and cognitive decline. Our tanycytic BoNT/B mouse model provides a robust platform for studying how these conditions progress over time, from prediabetic states to full-blown metabolic and cognitive disorders, and the mechanistic contribution of tanycytes to their development. The recognition of the impact of tanycytic transcytosis on hormone transport opens new avenues for developing targeted therapies that could address both metabolic disorders and their associated cognitive comorbidities, which often emerge or worsen with advancing age.

Agouti-Induced Anxiety-Like Behavior Is Mediated by Central Serotonergic Pathways in Zebrafish.

Overexpression of the agouti-signaling protein (asip1), an endogenous melanocortin antagonist, under the control of a constitutive promoter in zebrafish [Tg(Xla.Eef1a1:Cau.Asip1]iim4] (asip1-Tg) increases food intake by reducing sensitivity of the central satiety systems and abolish circadian activity rhythms. The phenotype also shows increased linear growth and body weight, yet no enhanced aggressiveness in dyadic fights is observed. In fact, asip1-Tg animals choose to flee to safer areas rather than face a potential threat, thus suggesting a potential anxiety-like behavior (ALB). Standard behavioral tests, i.e., the open field test (OFT), the novel object test (NOT), and the novel tank dive test (NTDT), were used to investigate thigmotaxis and ALB in male and female zebrafish. Results showed that the asip1-Tg strain exhibited severe ALB in every test, mainly characterized by pronounced freezing behavior and increased linear and angular swimming velocities. asip1-Tg animals exhibited low central serotonin (5-HT) and dopamine (DA) levels and high turnover rates, thus suggesting that central monoaminergic pathways might mediate melanocortin antagonist-induced ALB. Accordingly, the treatment of asip1-Tg animals with fluoxetine, a selective serotonin reuptake inhibitor (SSRI), reversed the ALB phenotype in NTDT as well as 5-HT turnover. Genomic and anatomical data further supported neuronal interaction between melanocortinergic and serotonergic systems. These results suggest that inhibition of the melanocortin system by ubiquitous overexpression of endogenous antagonist has an anxiogenic effect mediated by serotonergic transmission.

Energy Deficit is a Key Driver of Sleep Homeostasis.

Sleep and feeding are vital homeostatic behaviors, and disruptions in either can result in substantial metabolic consequences. Distinct neuronal manipulations in Drosophila can dissociate sleep loss from subsequent homeostatic rebound, offering an optimal platform to examine the precise interplay between these fundamental behaviors. Here, we investigate concomitant changes in sleep and food intake in individual animals, as well as respiratory metabolic expenditure, that accompany behavioral and genetic manipulations that induce sleep loss in Drosophila melanogaster. We find that sleep disruptions resulting in energy deficit through increased metabolic expenditure and manifested as increased food intake were consistently followed by rebound sleep. In contrast, "soft" sleep loss, which does not induce rebound sleep, is not accompanied by increased metabolism and food intake. Our results demonstrate that homeostatic sleep rebound is linked to energy deficit accrued during sleep loss. Collectively, these findings support the notion that sleep functions to conserve energy and highlight the need to examine the effects of metabolic therapeutics on sleep.

Use of Gabapentin or Alprazolam in Cats during Postoperative, Short-Term Hospitalization.

This prospective, randomized study aimed to assess the anxiolytic efficacy of gabapentin or alprazolam in cats during short-term postoperative hospitalization. Sixty cats were randomly assigned to three groups (gabapentin-treated [100 mg per cat], alprazolam-treated [0.125 mg per cat], or placebo-treated), with treatments administered twice daily for two days. Stress levels were evaluated using Cat Stress Scores, serum cortisol, and glucose concentrations. Pain scores, food consumption, and adverse effects such as sedation were also monitored. Fifty-five cats completed the study. Both medications demonstrated similar reductions in stress levels. Cats receiving gabapentin had lower pain scores, while those receiving alprazolam exhibited significantly increased food intake on the first postoperative day. However, both medications resulted in comparable levels of sedation. In the context of postoperative hospitalization, pharmacological intervention with anxiolytics could be effective in reducing stress levels. Despite potential side effects, gabapentin and alprazolam may contribute to an improved quality of short-term hospitalization for cats.

The association between COVID-19 related income loss and diet quality: The mediating role of distress

The COVID-19 lockdowns saw many individuals lose income, experience distress and increase intake of foods that would typically be considered less ‘healthy’ (more processed and less fresh produce). Establishing whether there are direct and indirect links between these variables would be of benefit in preparing for similar future events but also has implications for the current global financial climate, where many are experiencing relative decreases in income. Adults in two locations (UK and Australia) (N = 917) completed online questionnaires to explore the impact of the first COVID-19 lockdown on their change in income, emotional wellbeing (depression, anxiety, stress, loneliness), resilience and diet quality. A structural equation model revealed that income loss was indirectly associated with diet quality via distress. As such, the greater the loss of income experienced, the more distress reported; distress was then directly associated with a less nutritious diet. This pattern of results existed when data from both countries were combined but also when they were modelled individually. Our findings indicate that where individuals experience a sudden reduction of income there are likely to be negative consequences for both mental and physical health. It is plausible that these findings would extend to other circumstances in which sudden loss of income may be experienced such as reductions in state social care, rising inflation and interest rates and sudden increases to the general cost of living.

Protein-coding mutation in Adcy3 increases adiposity and alters emotional behaviors sex-dependently in rats.

Adenylate cyclase 3 (Adcy3) has been linked to both obesity and major depressive disorder (MDD). Our lab identified a protein-coding variant in the 2nd transmembrane (TM) helix of Adcy3 in rats, and similar obesity variants have been identified in humans. The current study investigates the role of a TM variant in adiposity and behavior. We used CRISPR-SpCas9 to mutate the TM domain of Adcy3 in WKY rats (Adcy3mut/mut). We also created a heterozygous knockout rat in the same strain (Adcy3+/-). Wild-type (WT), Adcy3+/-, and Adcy3mut/mut rats were fed a high-fat diet for 12 weeks. We measured body weight, fat mass, glucose tolerance, food intake, metabolism, emotion-like behaviors, and memory. Adcy3+/- and Adcy3mut/mut rats weighed more than WT rats due to increased fat mass. There were key sex differences: adiposity was driven by increased food intake in males but by decreased energy expenditure in females. Adcy3mut/mut males displayed increased passive coping and decreased memory while Adcy3mut/mut females displayed increased anxiety-like behavior. These studies show that the ADCY3 TM domain plays a role in protein function, that Adcy3 may contribute to the relationship between obesity and MDD, and that sex influences the relationships between Adcy3, metabolism, and behavior.