Decreased Food Intake Research Articles

Systemic Co-Administration of Low-Dose Oxytocin and Glucagon-Like Peptide 1 Additively Decreases Food Intake and Body Weight

Introduction: GLP-1 receptor agonists are the number one drug prescribed for the treatment of obesity and type 2 diabetes. These drugs are not, however, without side effects, and in an effort to maximize therapeutic effect while minimizing adverse effects, gut hormone co-agonists received considerable attention as new drug targets in the fight against obesity. Numerous previous reports identified the neuropeptide oxytocin (OXT) as a promising anti-obesity drug. The aims of this study were to evaluate OXT as a possible co-agonist for GLP-1 and examine the effects of its co-administration on food intake (FI) and body weight (BW) in mice. Methods: FI and c-Fos levels were measured in the feeding centers of the brain in response to an intraperitoneal injection of saline, OXT, GLP-1, or OXT/GLP-1. The action potential frequency and cytosolic Ca2+ ([Ca2+]i) in response to OXT, GLP-1, or OXT/GLP-1 were measured in ex vivo paraventricular nucleus (PVN) neuronal cultures. Finally, FI and BW changes were compared in diet-induced obese mice treated with saline, OXT, GLP-1, or OXT/GLP-1 for 13 days. Results: Single injection of OXT/GLP-1 additively decreased FI and increased c-Fos expression specifically in the PVN and supraoptic nucleus. Seventy percent of GLP-1 receptor-positive neurons in the PVN also expressed OXT receptors, and OXT/GLP-1 co-administration dramatically increased firing and [Ca2+]i in the PVN OXT neurons. The chronic OXT/GLP-1 co-administration decreased BW without changing FI. Conclusion: Chronic OXT/GLP-1 co-administration decreases BW, possibly via the activation of PVN OXT neurons. OXT might be a promising candidate as an incretin co-agonist in obesity treatment.

Incorporation of Three Extracyclic Arginine Residues into a Melanocortin Macrocyclic Agonist (c[Pro-His-DPhe-Arg-Trp-Dap-Lys(Arg-Arg-Arg-Ac)-DPro]) Decreases Food Intake When Administered Intrathecally or Subcutaneously Compared to a Macrocyclic Ligand Lacking Extracyclic Arginine Residues (c[Pro-His-DPhe-Arg-Trp-Dap-Ala-DPro)

Of the three Food and Drug Administration-approved melanocortin peptide drugs, two possess a cyclic scaffold, demonstrating that cyclized melanocortin peptides have therapeutic relevance. An extracyclic Arg residue, critical for pharmacological activity in the approved melanocortin cyclic drug setmelanotide, has also been demonstrated to increase the signal when fluorescently labeled cell-penetrating cyclic peptides are incubated with HeLa cells, with the maximal signal observed with three extracyclic Arg amino acids. Herein, a branching Lys residue was substituted into two macrocyclic melanocortin peptide agonists to incorporate 0-3 extracyclic Arg amino acids. Incorporation of the Arg residues resulted in equipotent or increased agonist potency at the mouse melanocortin receptors in vitro, suggesting that these substitutions were tolerated in the macrocyclic scaffolds. Further in vivo evaluation of one parent ligand (c[Pro-His-DPhe-Arg-Trp-Dap-Ala-Pro]) and the three Arg derivative (c[Pro-His-DPhe-Arg-Trp-Dap-Lys(Ac-Arg-Arg-Arg)-Pro)] demonstrated that the three Arg derivative further decreased food intake compared to the parent macrocycle when the compounds were administered either via intrathecal injection or subcutaneous dosing. This suggests that three extracyclic Arg amino acids may be beneficial in the design of cyclic melanocortin ligands and that in vitro pharmacological profiling may not predict the in vivo efficacy of melanocortin ligands.

Zearalenone Decreases Food Intake by Disrupting the Gut-Liver-Hypothalamus Axis Signaling via Bile Acids.

Zearalenone (ZEN) is a mycotoxin that is harmful to humans and animals. In this study, female and male rats were exposed to ZEN, and the results showed that ZEN reduced the farnesoid X receptor (FXR) expression levels in the liver and disrupted the enterohepatic circulation of bile acids (BAs). A decrease in food intake induced by ZEN was negatively correlated with an increase in the level of total BAs. BA-targeted metabolomics revealed that ZEN increased glycochenodeoxycholic acid levels and decreased the ratio of conjugated BAs to unconjugated BAs, which further increased the hypothalamic FXR expression levels. Preventing the increase in total BA levels induced by ZEN via Lactobacillus rhamnosus GG intervention restored the appetite. In conclusion, ZEN disrupted the enterohepatic circulation of BAs to decrease the level of food intake. This study reveals a possible mechanism by which ZEN affects food intake and provides a new approach to decrease the toxic effects of ZEN.

Case of lead poisoning secondary to intake of herbal medicine for diabetes mellitus in a tertiary care hospital in Kerala.

Although most published cases of lead poisoning come from occupational exposures, some traditional remedies may also contain toxic amounts of lead. Here, we report the case of a 58-year-old female who presented with abdominal pain, generalized tiredness, and decreased food intake, with anemia and elevated levels of lead. The patient was found to be taking herbal capsules for diabetes prior to the presentation. This case highlights the need for increased awareness that some herbal remedies may contain potentially harmful levels of heavy metals, and people who use them are at risk of developing associated toxicities. Individuals who support traditional medicine often incorrectly believe that herbal remedies for diabetes are free from side effects, leading them to favor these treatments over contemporary medications. Herbal medications are freely available online, even without a prescription. The accessibility of herbal medicines without prescriptions, coupled with the false belief in their lack of side effects, misleads educated individuals toward quackery treatments. Misinformation spread via social media exacerbates this issue. Heavy metals are present in toxic levels in the drugs, causing complications. Lead is the most common heavy metal found in such herbal medicines. Lead poisoning leads to anemia and other systemic complications which could have been fatal if not found in time.

Dysregulated metabolic sensing of appetite in anorexia nervosa: implications of LEAP-2 regulation

AbstractGrowing interests on the role of metabolic sensors in anorexia nervosa led to implicate metabolic sensing as consequences of anorectic sensing but also in the perpetuation of the disorder. Ghrelin is an orexigenic peptide secreted by the fundic cells of the stomach in situation of fasting and kown to initiate food intake through its activity on hypothalamic and motivation aspect of food intake. A body opf evidenc previously showed that patients suffering from anorexia nervosa display high plasma levels of ghrelin correlated with the nutritionnal status but his orexigenic signal do not seem to modify restrictive behavior. LEAP-2 (Liver Expressed Antimicrobial Peptide 2) is a recently discovered endogenous ghrelmin antagonist, increased during overnutrition and that decreases food intake in humans and animals.We explored ghanges of ghrelin and LEAP-2 in a longitudinal cohort of 30 patients suffering from anorexia nervosa during a 4 months refeeding program. We show abnormal regulation of LEAP-2 in patients with higher levels in acute stages that decrease with refeeding. This abnormal regulation was associated with early relapse in patients. This abnormal regulation could counteract with the orexigenic signal of ghrelin in patients.We discuss these results in light with recent evidence on the consequences of LEAP-2 increase of food intake and hedonic feeding relevant in understanding anorexia nervosa.Disclosure of InterestNone Declared

Subcutaneous hydromorphone hydrochloride provides antinociception with transient adverse effects in four-toed hedgehogs (Atelerix albiventris).

To evaluate the efficacy and safety of hydromorphone administered SC in four-toed hedgehogs (Atelerix albiventris). 12 healthy adult hedgehogs. Hedgehogs underwent 2 randomized, blinded, placebo-controlled, complete crossover studies. Hind limb withdrawal latencies in response to an acute thermal noxious stimulus were measured to evaluate the antinociceptive efficacy of hydromorphone. Baseline latencies were obtained prior to injection and collected again at 0.5, 1, 2, 4, and 6 hours following injection. Based on pilot studies, single doses of SC hydromorphone at 0.15 and 0.3 mg/kg were evaluated for efficacy in crossover trials. Safety of single (0.15 and 0.3 mg/kg) and multiple doses of hydromorphone (0.3 mg/kg, SC, q 4 h, for 3 doses) was also assessed. In addition to monitoring behavior during latency measurements, animals were evaluated for overt sedation and daily changes in food intake, body weight, and running wheel activity for 6 days after injection to evaluate for adverse effects. Hydromorphone at 0.15 mg/kg provided antinociception lasting < 4 hours, and 0.3 mg/kg provided antinociception lasting < 6 hours. Hydromorphone produced transient abnormal behaviors at both doses, including vocalization, chewing motions of the jaw, and paw raising. There were no statistically significant differences in body weight or running wheel activity between treatments for single or multiple doses of hydromorphone. Three doses of 0.3 mg/kg hydromorphone (q 4 h) produced a statistically significant decrease (median, -9.7%; range, -64% to 10%) in 6-day total food intake. Subcutaneous hydromorphone (0.15 to 0.3 mg/kg) can be used for short-term antinociception with transient adverse effects in hedgehogs.

Feasibility of a screening and prevention procedure for risks associated with dysphagia in older patients in geriatric units: the DYSPHAGING pilot study protocol

BackgroundDysphagia, particularly sarcopenic dysphagia, is frequent in frail older patients. Sarcopenic dysphagia is a swallowing disorder caused by sarcopenia, corresponding to a loss of muscle mass and strength. It frequently...

Effects of meloxicam on the welfare of Holstein calves from 6 weeks to 6 months old undergoing amputation dehorning

Amputation dehorning (AD) is a common practice performed on calves, causing harmful effects such as pain, distress, anxiety, and fear. These effects extend to behavioral, physiological, and hematological responses, prompting serious ethical concerns regarding animal welfare, even when performed with local anesthesia. Meloxicam, a nonsteroidal anti-inflammatory drug, has been widely used to mitigate the side effects of dehorning and disbudding in calves. However, there is a notable gap in research regarding the effects of meloxicam on calves aged 6 wk to 6 mo undergoing AD procedures. This study was designed to assess the effectiveness of co-administering meloxicam with lidocaine, a cornual nerve anesthetic, in alleviating the adverse effects caused by the AD procedure in calves within this age range, compared with the use of lidocaine alone. Thirty Holstein calves were enrolled and randomly divided into 2 groups. The first group received a subcutaneous injection of 5 mL of lidocaine in the horn area and a subcutaneous injection of 0.9% saline at a dose of 0.025 mL/kg in the neck, administered 10 min before the AD procedure. The second group received a combination of lidocaine and meloxicam: a subcutaneous injection of 5 mL of lidocaine in the horn area and a subcutaneous injection of 20 mg/mL meloxicam at a dose of 0.025 mL/kg in the neck, also administered 10 min before the AD procedure. To avoid subjective bias, the researchers were blinded to the treatment groups. Pain-related behaviors, including tail flicking, head shaking, ear flicking, head rubbing, head crossing bar, and kicking, were observed, and physiological parameters, including heart rate, rectal temperature, respiration rate, mechanical nociceptive threshold (MNT), daily active steps, and food intake were monitored. Hematological conditions were determined using enzyme-linked immunosorbent assays and routine blood tests. The data were processed using a generalized linear mixed model. The outcomes demonstrated that the AD procedure increased the frequencies of ear flicking and resulted in rises in the respiration rate, heart rate, rectal temperature, and daily active steps. It also led to decreases in total food intake, forage intake, hay intake, MNT, and increased concentrations of prostaglandin E2 (PgE2), IL-1β, tumor necrosis factor-α (TNF-α), nitric oxide (NO), and malondialdehyde, as well as glutathione peroxidase activity. However, calves that received meloxicam treatment showed significant improvements in response to the AD procedure, including lower respiration rates, heart rates, and rectal temperatures; higher MNT; and lower intermediate cell ratio. They also had higher red blood counts, hemoglobin levels, hematocrit values; larger mean platelet volumes; and lower concentrations of PgE2, IL-1β, TNF-α, and NO. These results suggest that co-administration of lidocaine and meloxicam may aid in mitigating the adverse effects induced by the AD procedure on these calves, thereby supporting the use of meloxicam in conjunction with a local anesthetic in AD procedures for calves aged 6 wk to 6 mo.

Development of Multi-particulate Formulation of Glabridin with L-Phenylalanine and Its Pre-clinical Evaluation for Anti-obesity Activity

Obesity is a chronic condition that is defined by pathophysiological mechanisms that lead to an increase in adipose tissue mass as a result of positive energy balance. Obesity is a multi-factorial disorder involving different mechanisms of action like humoral and neurogenic actions. Hypertrophied and hyperplastic adipocytes are indicative of pathological obesity. In the current treatment regimen, the drugs used mainly focus on a single mechanism of action. Herbal medicines are reported to have anti-obesity activity but due to the presence of multiple phytoconstituents its very difficult for one to finalize the dose and issue of palatability. So the best solution is to focus on usage of active phytoconstituent as an anti-obesity medicine. A high protein diet proved to have anti-obesity activity, the main constituent responsible for this activity is L-phenylalanine which is an essential amino acid that produces its activity by stimulating the satiety centre and thus decreases food intake. In this study, we are combining glabridin from Glycyrrhiza glabra and L-phenylalanine as both show anti-obesity activity through different action mechanisms, which may result in synergism. The study aims to prepare multi-particulate system (granules) of glabridin with L-phenylalanine and evaluate their anti-obesity and hypo-lipidemic action in HFD-treated rats.

Nucleus accumbens D1- and D2-expressing neurons control the balance between feeding and activity-mediated energy expenditure

Accumulating evidence points to dysregulations of the Nucleus Accumbens (NAc) in eating disorders (ED), however its precise contribution to ED symptomatic dimensions remains unclear. Using chemogenetic manipulations in male mice, we found that activity of dopamine D1 receptor-expressing neurons of the NAc core subregion facilitated effort for a food reward as well as voluntary exercise, but decreased food intake, while D2-expressing neurons have opposite effects. These effects are congruent with D2-neurons being more active than D1-neurons during feeding while it is the opposite during running. Chronic manipulations of each subpopulations had limited effects on energy balance. However, repeated activation of D1-neurons combined with inhibition of D2-neurons biased behavior toward activity-related energy expenditure, whilst the opposite manipulations favored energy intake. Strikingly, concomitant activation of D1-neurons and inhibition of D2-neurons precipitated weight loss in anorexia models. These results suggest that dysregulations of NAc dopaminoceptive neurons might be at the core of EDs.

Older adults' acceptability of and preferences for food-based protein fortification in the UK, France and Norway.

Research suggests that as we age, protein intake, recognised as vital for combating negative health outcomes, consistently falls below recommendations in older adults. Decreased food intake, combined with age-related eating complications is a major determinant of this protein undernutrition. If nutritional interventions are to be effective and sustainable, they must enable eating pleasure, cater for personal preferences and be adaptable to different eating patterns. As such, we aimed to identify successful strategies for at-home protein-fortification to empower older adults to take a personalised approach to their nutrition, without requiring a large behavioural change. To explore healthy older adults’ (age 70+) acceptability and preferences for at-home protein fortification, European project Fortiphy led discussions with older adults (n = 37) and caregivers of older adults (n = 15) to develop high-protein recipes, which were then utilised in a home-use trial with healthy older adults (n = 158). Each fortified recipe was paired with a questionnaire to rate the ease of preparation and liking, and an end-of-study questionnaire was provided to capture overall opinions and preferences. The uniqueness of this study is that the protein fortified recipes were prepared and tested by older adults themselves, in their own homes. Findings showed that older adults were unaware of the importance of protein in ageing and did not have a desire to fortify their foods at present. Yet, they were positive regarding the concept and highlighted the importance of taste, familiar ingredients, and preferred preparation methods. Cultural preferences across countries were identified as having the most influence on the liking of fortified meals. This study also indicated a need for increased awareness of protein requirements to influence the motivation to use fortification.

The influence of nutritional status and associated factors on the quality of life among COVID-19 patients in Saudi Arabia: A cross-sectional study

BackgroundCOVID-19 adversely affects the nutritional characteristics of patients which may negatively impact their quality of life (QOL). The current study determined the association between the nutritional status of COVID-19 patients, its impact on their QOL, and the factors that affected patients' QOL. MethodsA cross-sectional study was conducted at Al Madinah Al Munawarah in Saudi Arabia. Patients confirmed with COVID-19 infection by a nucleic acid-positive test and identified as acute severe or acute non-severely ill were enrolled. The World Health Organization Quality of Life Questionnaire (WHO-BREF QOL) was used to assess the patients' QOL, and nutritional status was assessed using the Malnutrition Screening Tool. Demographic characteristics, food intake, and body mass index (BMI) were also assessed. Data was analyzed using SPSS version 28. Results515 patients were enrolled, with 391 (76%) having acute non-severe symptoms. Patients (15%) were malnourished and suffered from loss of appetite (32%), low food intake (19.4%) and weight loss (16%). Most patients were satisfied or very satisfied with their health (80.2%), and 76.2% rated their QOL as good or very good. Loss of appetite negatively impacted the physical (p = 0.004, 95% CI 0.086, 0.458) and psychological (p = 0.021, 95% CI 0.034, 0.405) QOL domains. Also, decreased food intake affected patients' physical (p = 0.034, 95% CI 0.018, 0.458) QOL domain. Greater weight loss influenced the psychological (p = 0.005.95% CI 0.002, 0.049) QOL domain. ConclusionsPoor nutritional status among COVID-19 patients was associated with adverse health outcomes and impaired QOL. Nutritional interventions should focus on patients with poor nutritional status or nutrition-related parameters such as weight loss, and loss of appetite which will help improve their QOL.

Protective effect of alpha‑lipoic acid against in utero cytarabine exposure-induced hepatotoxicity in rat female neonates.

Cytarabine, an anti-metabolite drug, remains the mainstay of treatment for hematological malignancies. It causes various toxic effects including teratogenicity. Alpha lipoic acid (ALA) is a natural antioxidant reported to offer protection against hepatotoxicity induced by various pathological conditions, drugs, or chemicals. We investigated the protective effect of ALA against prenatal cytarabine exposure-induced hepatotoxicity in rat female neonates. A total of 30 dams were randomly assigned to five groups and received normal saline, ALA 200 mg/kg, cytarabine 12.5 mg/kg, cytarabine 25 mg/kg, and cytarabine 25 mg/kg + ALA 200 mg/kg, respectively, from gestational day (GD)8 to GD21. Cytarabine and ALA were administered via intraperitoneal and oral (gavage) routes, respectively. On postnatal day (PND)1, all the live female neonates (pups) were collected and weighed. The blood and liver from pups were carefully collected and used for histopathological, and biochemical evaluations. A significant and dose-dependent decrease in maternal food intake and weight gain was observed in the pregnant rats (dams) of the cytarabine groups as compared to the dams of the control group. The pups exposed to cytarabine showed a significant and dose-dependent (a) decrease in body weight, liver weight, hepatosomatic index, catalase, superoxide dismutase, glutathione, glutathione peroxidase, serum albumin levels and (b) increase in malondialdehyde, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, AST/ALT ratio, and histopathological anomalies. Maternal co-administration of ALA ameliorated these biochemical changes and histopathological abnormalities by combating oxidative stress. Future studies are warranted to explore the molecular mechanisms involved in the ALA's protective effects against prenatal cytarabine-induced hepatotoxicity.

Exercise alleviates cisplatin-induced toxicity in the hippocampus of mice by inhibiting neuroinflammation and improving synaptic plasticity.

Chemotherapy-induced cognitive impairment is recognized as the most typical symptom in patients with cancer that occurs during and following the chemotherapy treatment. Recently many studies focused on pharmaceutical strategies to control the chemotherapy side effects, however it is far from satisfactory. There may be a need for more effective treatment options. The aim of this study was to investigate the protective effect of exercise on cisplatin-induced neurotoxicity. Eightweek- old C57BL6 mice were separated into three group: normal control (CON, n = 8); cisplatin injection control (Cis-CON, n = 8); cisplatin with aerobic exercise (Cis-EXE, n = 8). Cisplatin was administered intraperitoneally at a dose of 3.5 mg/kg/day. The Cis-EXE group exercise by treadmill running (14-16 m/min for 45 min daily, 3 times/ week) for 12 weeks. Compared to the CON group, the cisplatin injection groups showed significant decrease in body weight and food intake, indicating successful induction of cisplatin toxicity. The Cis-CON group showed significantly increased levels of pro-inflammatory cytokines including IL-6, IL-1β, and TNF-α in the hippocampus, while the Cis-EXE group was significantly decreased in the expression of IL- 6, IL-1β, and TNF-α. In addition, compared to the CON group, the levels of synapserelated proteins including synapsin-1 and -2 were significantly reduced in the Cis- CON group, and there was a significant difference between the Cis-CON and Cis-EXE groups. Antioxidant and apoptosis factors were significantly improved in the Cis-EXE group compared with the Cis-CON group. This study suggest that exercise could be meaningful approach to prevent or improve cisplatin-induced cognitive impairment.

Stress-induced changes in cognitive function and intestinal barrier integrity can be ameliorated by venlafaxine and synbiotic supplementations.

Stress profoundly impacts various aspects of both physical and psychological well-being. Our previous study demonstrated that venlafaxine (Vlx) and synbiotic (Syn) treatment attenuated learned fear-like behavior and recognition memory impairment in immobilized-stressed rats. In this study, we further investigated the physical, behavior, and cellular mechanisms underlying the effects of Syn and/or Vlx treatment on brain and intestinal functions in stressed rats. Adult male Wistar rats, aged 8 weeks old were subjected to 14 days of immobilization stress showed a decrease in body weight gain and food intake as well as an increase in water consumption, urinary corticosterone levels, and adrenal gland weight. Supplementation of Syn and/or Vlx in stressed rats resulted in mitigation of weight loss, restoration of normal food and fluid intake, and normalization of corticosterone levels. Behavioral analysis showed that treatment with Syn and/or Vlx enhanced depressive-like behaviors and improved spatial learning-memory impairment in stressed rats. Hippocampal dentate gyrus showed stress-induced neuronal cell death, which was attenuated by Syn and/or Vlx treatment. Stress-induced ileum inflammation and increased intestinal permeability were both effectively reduced by the supplementation of Syn. In addition, Syn and Vlx partly contributed to affecting the expression of the glial cell-derived neurotrophic factor in the hippocampus and intestines of stressed rats, suggesting particularly protective effects on both the gut barrier and the brain. This study highlights the intricate interplay between stress physiological responses in the brain and gut. Syn intervention alleviate stress-induced neuronal cell death and modulate depression- and memory impairment-like behaviors, and improve stress-induced gut barrier dysfunction which were similar to those of Vlx. These findings enhance our understanding of stress-related health conditions and suggest the synbiotic intervention may be a promising approach to ameliorate deleterious effects of stress on the gut-brain axis.

Peripheral administration of lipidized NPAF and NPFF analogs does not influence central food intake regulation but induces anxiety-like behavior

RF-amide peptides influence multiple physiological processes, including the regulation of appetite, stress responses, behavior, and reproductive and endocrine functions. In this study, we examined the roles of neuropeptide FF receptors (NPFFR1 and NPFFR2) by generating several lipidized analogs of neuropeptide AF (NPAF) and 1DMe, a stable analog of neuropeptide FF (NPFF). These analogs were administered peripherally for the first time to investigate their effects on food intake and other potential physiological outcomes. Lipidized NPAF and 1DMe analogs exhibited enhanced stability and increased pharmacokinetics. These analogs demonstrated preserved high affinity for NPFFR2 in the nanomolar range, while the binding affinity for NPFFR1 was tens of nanomoles. They activated the ERK and Akt signaling pathways in cells overexpressing the NPFFR1 and NPFFR2 receptors.Acute food intake in fasted mice decreased after the peripheral administration of oct-NPAF or oct-1DMe. However, this effect was not as pronounced as that observed after the injection of palm11-PrRP31, a potent anorexigenic compound used as a comparator that binds to GPR10 and the NPFFR2 receptor with high affinity. Neither oct-1DMe nor oct-NPAF decreased food intake or body weight in mice with diet-induced obesity during long-term treatment. In mice treated with oct-1DMe, we observed decreased activity in the central zone during the open field test and decreased activity in the open arms of the elevated plus maze. Furthermore, we observed a decrease in plasma noradrenaline levels and an increase in plasma corticosterone levels, as well as an increase in Crh expression in the hypothalamus. Moreover, neuronal activity in the hypothalamus was increased after treatment with oct-1DMe.In this study, we report that oct-1DMe did not have any long-term effects on the central regulation of food intake; however, it caused anxiety-like behavior.

Adenine's impact on mice's gut and kidney varies with the dosage administered and relates to intestinal microorganisms and enzyme activities.

This study aimed to investigate the effects of different dosages of adenine on intestinal microorganisms and enzyme activities, laying the experimental groundwork for subsequent exploration of the microbial mechanisms underlying diarrhea with kidney yang deficiency syndrome. Twenty-four mice were assigned to the following four groups: the control (NC) group, low-dosage adenine (NML) group, middle-dosage adenine (NMM) group, and high-dosage adenine (NMH) group. Mice in the NML, NMM, and NMH groups received 25mg/(kg·d), 50mg/(kg·d), and 100mg/(kg·d) of adenine, respectively, 0.4mL/each, once a day for 14days. The NC group received 0.4mL sterile water. Parameters including body weight, rectal temperature, intestinal microorganisms, enzyme activities, and microbial activity were measured. Results indicated that mice in the experimental group displayed signs of a poor mental state, curled up with their backs arched, and felt sleepy and lazy, with sparse fur that was easily shed, and damp bedding. Some mice showed fecal adhesion contamination in the perianal and tail areas. Dosage-dependent effects were observed, with decreased food intake, body weight, rectal temperature, and microbial activity and increased water intake and fecal water content. Enzyme activity analyses revealed significantly higher activities of protease, sucrase, amylase, and cellulase in intestinal contents and lactase, sucrase, amylase, and cellulase in the mucosa of the NMM group compared to those of other groups. Ultimately, the higher adenine dosage was associated with more pronounced symptoms of kidney yang deficiency syndrome, with 50mg/kg adenine exhibiting the most substantial impact on the number of intestinal microbial colonies and enzyme activities.

Prevalence of the use of oral nutritional supplements among acute inpatients at risk of malnutrition and associated patient characteristics.

To provide a snapshot of the current use of oral nutritional supplements, its association with inpatient characteristics, and with a focus on the role of nursing monitoring of food intake and implementing nutritional interventions for patients with low intake. Retrospective cohort study. The study collected data from a hospital database regarding oral nutritional supplement initiation and variables of patients hospitalised in internal medicine departments, who did not receive enteral or parenteral nutrition. Of the 5155 admissions, 1087 fulfilled the inclusion criteria (47% female; mean age, 72.4 ± 14.6 years; mean length of stay, 14.6 ± 11.4 days). Sufficient food intake reporting was noted in 74.6% of the patients; of these 17% had decreased intake. Oral nutritional supplements and non-oral nutritional supplements groups did not differ in terms of sex, age, length of stay, Charlson Comorbidity Index, proportion of nursing reports, and absence of intake monitoring. Oral nutritional supplements were initiated in 31.9% of patients with a Malnutrition Universal Screening Tool score ≥2 and in 34.6% with decreased food intake. On multivariable analysis, hypoalbuminemia (adjusted odds ratio, 3.70), decreased food intake (adjusted odds ratio, 3.38), Malnutrition Universal Screening Tool score ≥2 (adjusted odds ratio, 2.10), and age <70 years (adjusted odds ratio, 1.56) were significantly associated with oral nutritional supplements use. The prevalence of oral nutritional intervention was suboptimal in patients at risk of malnutrition during acute hospitalisation, although decreased food intake and Malnutrition Universal Screening Tool score ≥2 independently increased the probability of oral nutritional supplements initiation. Understanding the clinical practice and nursing impact of care management in relation to nutritional intervention can assist in reviewing and improving patient care. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE IMPACT (ADDRESSING): This study informs clinical management and influences nursing practice standards related to assessing, monitoring, and managing malnutrition risk. The study impacts the quality of care for patients at risk of malnutrition. We adhered to the STROBE Checklist for cohort studies. No Patient or Public Contribution.

Beneficial effects of simultaneously targeting calorie intake and calorie efficiency in diet-induced obese mice.

Semaglutide is an anti-diabetes and weight loss drug that decreases food intake, slows gastric emptying, and increases insulin secretion. Patients begin treatment with low-dose semaglutide and increase dosage over time as efficacy plateaus. With increasing dosage, there is also greater incidence of gastrointestinal side effects. One reason for the plateau in semaglutide efficacy despite continued low food intake is due to compensatory actions whereby the body becomes more metabolically efficient to defend against further weight loss. Mitochondrial uncoupler drugs decrease metabolic efficiency, therefore we sought to investigate the combination therapy of semaglutide with the mitochondrial uncoupler BAM15 in diet-induced obese mice. Mice were fed high-fat western diet (WD) and stratified into six treatment groups including WD control, BAM15, low-dose semaglutide without or with BAM15, and high-dose semaglutide without or with BAM15. Combining BAM15 with either semaglutide dose decreased body fat and liver triglycerides, which was not achieved by any monotherapy, while high-dose semaglutide with BAM15 had the greatest effect on glucose homeostasis. This study demonstrates a novel approach to improve weight loss without loss of lean mass and improve glucose control by simultaneously targeting energy intake and energy efficiency. Such a combination may decrease the need for semaglutide dose escalation and hence minimize potential gastrointestinal side effects.

Suppressive Effects of Neuromedin U Receptor 2-Selective Peptide Agonists on Appetite and Prolactin Secretion in Mice.

Neuromedin U receptor 2 (NMUR2), which is expressed in the central nervous system (CNS) including the hypothalamus, has been noted as a therapeutic target against obesity. We previously reported that intranasal administration of CPN-219, a NMUR2-selective hexapeptide agonist, suppresses body weight gain in mice; however, there is no detailed information regarding its CNS effects. Recently, in addition to appetite suppression, stress responses and regulation of prolactin (PRL) secretion have also attracted attention. NMUR2 expressed in the hypothalamic tuberoinfundibular dopaminergic neurons has emerged as an alternative target for treating hyperprolactinemia. Here, CPN-219 decreased food intake up to 24 h after administration at a dose of 200 nmol, resulting in body weight gain suppression, although grooming and anxiety-like behaviors were transiently induced. Interestingly, the restraint stress-induced increase in plasma PRL levels was significantly suppressed at a lower dose of 20 nmol, indicating the potential for drug development as an anti-PRL agent of NMUR2-selective agonists.