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ABSTRACT: This novel study investigated the effects of intracerebroventricular (ICV) injection α- klotho and its interaction with neuropeptide Y (NPY) receptors on food intake in broiler chicken. This study included 4 experiments with 4 groups in each with 11 replicates per group. Birds were feed deprived 3 h prior injection, following injection returned to their cage and food provided. In experiment 1, group 1 received ICV injection of the saline and groups 2 to 4 received ICV injection of the α-klotho (1, 2, and 4 µg), respectively. In experiment 2, chicken received ICV injection of the saline, B5063 (NPY1 receptor antagonist, 1.25 µg), α-klotho (4 µg) and co-injection of the B5063 + α-klotho. In experiments 3 and 4, SF22 (NPY2 receptor antagonist, 1.25 µg), and SML0891 (NPY5 receptor antagonist, 1.25 µg) were injected instead of the B5063. Then consumed food was measured at 30, 60, and 120 min post the injection. Based on results, ICV injection of the α-klotho (2 and 4 µg) significantly decreased food intake (P < 0.05). Co-injection of the B5063 + α-klotho significantly amplified hypophagic effect of the α-klotho (P < 0.05). α-klotho-induced hypophagia was not influenced by SF22 or SML0891. These results suggest that α-klotho-induced hypophagia is mediated via NPY1 receptors in broiler chicken.

Understanding the detailed mechanism of action of glucagon-like peptide 1 receptor (GLP-1R) agonists on distinct topographic and genetically-defined brain circuits is critical for improving the efficacy and mitigating adverse side effects of these compounds. In this mini-review, we propose that the central nucleus of the amygdala (CeA) is a critical mediator of GLP-1R agonist-driven hypophagia. Here, we review the extant literature demonstrating CeA activation via GLP-1R agonists across multiple species and through multiple routes of administration. The precise role of GLP-1Rs within the CeA is unclear but the site specific GLP-1Rs may mediate distinct behavioral and physiological hallmarks of GLP-1R agonists on food intake. Thus, we propose important novel directions and methods to test the role of the CeA in mediating GLP-1R actions., (© The Author(s) 2025. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.)

Rodents develop activity-based anorexia (ABA) when exposed to a restricted feeding schedule and allowed free access to a running wheel. These conditions lead to a life-threatening reduction in body weight. However, rodents exposed to only one of these conditions ultimately adapt to re-establish normal body weight. Although increased running coupled with reduction in voluntary food intake appear paradoxical under ABA conditions, ABA behavior is observed across numerous mammalian species. The ABA paradigm provides an animal model for anorexia nervosa (AN), an eating disorder with severe dysregulation of appetite-behavior. Subjects are singly housed with free access to a running wheel. Each day, the subject is offered food for a limited amount of time. During the course of the experiment, a subject's body weight decreases from high activity and low caloric intake. The duration of the study varies based on how long food is offered daily, the type of food offered, the strain of mouse, if drugs are being tested, and environmental factors. A lack of effective pharmacological treatments for AN patients, their low quality of life, high cost of treatment, and their high mortality rate indicate the urgency to further research AN. We provide a basic outline for performing ABA experiments with mice, offering a method to investigate AN-like behavior in order to develop novel therapies. This protocol is optimized for use in Balb/cJ mice, but can easily be manipulated for other strains, providing great flexibility in working with different questions, especially related to genetic factors of ABA.

Depression is a common comorbid diagnosis in patients with eating disorders (EDs). The development of pathogenetic therapy for depression with EDs is far from being completed.The objective of the psychopharmacotherapeutic study was to evaluate the efficacy and tolerability of melatonergic monotherapy with the antidepressant agomelatine (25–50 mg/day at night) for depressions with two ED variants: hyperphagic (n=32) and hypo- and aphagic (n=31) EDs.Patients and methods. The investigation enrolled patients of both sexes, aged 18 to 65 years. The investigators performed clinical psychopathological and experimental psychological studies, as well as psychometric examination using the 21-item Hamilton Depression Rating Scale (HDRS-21), the Clinical Global Impression (CGI), the Supplemental Hospital Offset Payment Program (SHOPP), the Dutch Eating Behavior Questionnaire (DEBQ), and statistical data processing.Results and discussion. There was a significant pronounced antidepressant effect of 6-week agomelatine therapy for depressions occurring with different ED variants both in the pattern of the depressive symptom complex and in that of concurrent with and preceding the latter. At the same time, the efficacy of the drug did not depend on the clinical presentations of the leading hypothymic syndrome, the variants of EDs, and the duration of actual depression. However, by the end of the study period, a larger effect was achieved in the therapy for depressions with the hyperphagic variant of EDs, as well as in patients with EDs manifesting in the pattern of depressive symptom complex. Agomelatine has a favorable tolerance profile. BMI tends to become normal in patients with different variants of EDs during the therapy. The adverse events are transient and/or unclear; they do not require therapy discontinuation.Conclusion. Agomelatine is an effective and relatively safe drug that can be recommended to treat depressions concurrent with EDs in therapeutic dosages for at least 6 weeks.

Background: Adverse life experiences are a major risk factor for anorexia nervosa (AN). Eating-provoked anxiousness associated with AN is postulated to be due to food-related exaggerated serotonin activity in the brain and imbalances of monoamine neurotransmitters.Objectives: Using a rodent model of stress-induced hypophagia, we investigated if stress exposure augments food-related serotonin turnover and imbalances in measures of brain serotonin and dopamine activity in manners consistent with anxiousness toward food and restricted eating.Methods: Adult male F344 rats were conditioned to associate an audio cue with daily food over 2 weeks, after which half of the rats were exposed to a single episode of tail shocks (stress) or left undisturbed (nonstressed). All rats were killed 48 h later, during a control period, the food-associated cue, or a period of food access. Serotonin, dopamine, and norepinephrine, as well as metabolite concentrations, were assessed across brain regions comprising reward, emotion, and feeding circuits relevant to AN in acutely stressed and nonstressed rats using HPLC. Statistical significance level was 5%.Results: Stress-induced rat hypophagia paralleled an augmented serotonin turnover in response to the food-associated cue in the hypothalamus and hippocampus, as well as food access in the hypothalamus and cortical areas (all P < 0.05). Stress exposure increased the ratio of serotonin to dopamine metabolites across several brain areas, but the magnitude of this imbalance was further augmented during the food-associated cue and food access in the brainstem, hippocampus, and cortical areas (all P < 0.05). Finally, stress lowered norepinephrine concentrations by 18% in the hypothalamus (P < 0.05).Conclusions: The observed stress-induced changes to monoamine profiles in rats could have key implications for physiological states that contribute to restricted eating and may hold relevance for the development of AN precipitated by adverse life experiences. [ABSTRACT FROM AUTHOR]

Eating behaviors of animals living in naturalistic environments offer unique insights into several dysregulated eating patterns observed in humans. Social subordination is a known precipitant of hyperphagia and hypophagia in human beings, and examples of similar responses have been identified in a phylogenetically widespread range of vertebral species. This points to potentially conserved, patterned responses to animals navigating lives within social hierarchies. Self-imposed food restriction in subordinate fish and hyperphagic responses in socially subordinated bird and primate individuals may represent evolved adaptations to the stress of social subordination. As such, hyperphagic and hypophagic responses to social subordination in these species may model the natural history, neurobiology, and behavioral ecology of human dieting and bingeing more accurately than some current animal models.Phylogenetically widespread similarities in eating patterns under the stress of social subordination point to potentially shared biological benefits of these behaviors across species and the role of evolutionary trade-offs, adaptations, and other processes in shaping them. The application of a broadly comparative lens to disordered eating behaviors in other species exposes important similarities and differences between neurophysiology of eating across species. In doing so, it highlights the value of phylogenetic analyses and macroevolution as tools for identifying novel, naturally occurring models for understanding disordered human eating. Moreover, this approach introduces the intriguing possibility that human cultural influences on disordered eating may have far more ancient origins than previously considered.

Eating behaviors of animals living in naturalistic environments offer unique insights into several dysregulated eating patterns observed in humans. Social subordination is a known precipitant of hyperphagia and hypophagia in human beings, and examples of similar responses have been identified in a phylogenetically widespread range of vertebral species. This points to potentially conserved, patterned responses to animals navigating lives within social hierarchies. Self-imposed food restriction in subordinate fish and hyperphagic responses in socially subordinated bird and primate individuals may represent evolved adaptations to the stress of social subordination. As such, hyperphagic and hypophagic responses to social subordination in these species may model the natural history, neurobiology, and behavioral ecology of human dieting and bingeing more accurately than some current animal models. Phylogenetically widespread similarities in eating patterns under the stress of social subordination point to potentially shared biological benefits of these behaviors across species and the role of evolutionary trade-offs, adaptations, and other processes in shaping them. The application of a broadly comparative lens to disordered eating behaviors in other species exposes important similarities and differences between neurophysiology of eating across species. In doing so, it highlights the value of phylogenetic analyses and macroevolution as tools for identifying novel, naturally occurring models for understanding disordered human eating. Moreover, this approach introduces the intriguing possibility that human cultural influences on disordered eating may have far more ancient origins than previously considered. [ABSTRACT FROM AUTHOR]

Some persistent hydrophobic pollutants biomagnify, i.e., achieve higher contaminant levels in a predator than in its prey ( C predator / C prey ) for three zoo-housed polar bears who experience seasonal periods of hyperphagia and hypophagia. All bears had high biomagnification capabilities (BMF lim ) and feces-based biomagnification factor (BMF F ) for three zoo-housed polar bears who experience seasonal periods of hyperphagia and hypophagia. All bears had high biomagnification capabilities (BMF lim was up to 200) owing to very efficient lipid assimilation (up to 99.5%). The bears differed up to a factor of 3 in their BMF lim . BMF lim and BMF F of a bear increased by up to a factor of 4 during the hypophagic period, when the ingestion rate was greatly reduced. Much of that variability can be explained by differences in the lipid assimilation efficiency, even though this efficiency ranged only from 98.1 to 99.5%. A high BMF lim was associated with a high abundance of Bacteroidales and Lachnospirales in the gut microbiome. Biomagnification varies to a surprisingly large extent between individuals and within the same individual over time. Future work should investigate whether this can be attributed to the influence of the gut microbiome on lipid assimilation by studying more individual bears at different key physiological stages.

Summary: Glucagon-like peptide-1 receptor (GLP-1R) agonists used to treat type 2 diabetes mellitus often produce nausea, vomiting, and in some patients, undesired anorexia. Notably, these behavioral effects are caused by direct central GLP-1R activation. Herein, we describe the creation of a GLP-1R agonist conjugate with modified brain penetrance that enhances GLP-1R-mediated glycemic control without inducing vomiting. Covalent attachment of the GLP-1R agonist exendin-4 (Ex4) to dicyanocobinamide (Cbi), a corrin ring containing precursor of vitamin B12, produces a “corrinated” Ex4 construct (Cbi-Ex4). Data collected in the musk shrew (Suncus murinus), an emetic mammal, reveal beneficial effects of Cbi-Ex4 relative to Ex4, as evidenced by improvements in glycemic responses in glucose tolerance tests and a profound reduction of emetic events. Our findings highlight the potential for clinical use of Cbi-Ex4 for millions of patients seeking improved glycemic control without common side effects (e.g., emesis) characteristic of current GLP-1 therapeutics.

In rats, overnight fasting reduces the ability of systemic cholecystokinin-8 (CCK) to suppress food intake and to activate cFos in the caudal nucleus of the solitary tract (cNTS), specifically within glucagon-like peptide-1 (GLP-1) and noradrenergic (NA) neurons of the A2 cell group. Systemic CCK increases vagal sensory signaling to the cNTS, an effect that is amplified by leptin and reduced by ghrelin. Since fasting reduces plasma leptin and increases plasma ghrelin levels, we hypothesized that peripheral leptin administration and/or antagonism of ghrelin receptors in fasted rats would rescue the ability of CCK to activate GLP-1 neurons and a caudal subset of A2 neurons that coexpress prolactin-releasing peptide (PrRP). To test this, cFos expression was examined in ad libitum-fed and overnight food-deprived (DEP) rats after intraperitoneal CCK, after coadministration of leptin and CCK, or after intraperitoneal injection of a ghrelin receptor antagonist (GRA) before CCK. In fed rats, CCK activated cFos in ~60% of GLP-1 and PrRP neurons. Few or no GLP-1 or PrRP neurons expressed cFos in DEP rats treated with CCK alone, CCK combined with leptin, or GRA alone. However, GRA pretreatment increased the ability of CCK to activate GLP-1 and PrRP neurons and also enhanced the hypophagic effect of CCK in DEP rats. Considered together, these new findings suggest that reduced behavioral sensitivity to CCK in fasted rats is at least partially due to ghrelin-mediated suppression of hindbrain GLP-1 and PrRP neural responsiveness to CCK. [ABSTRACT FROM AUTHOR]

Anorexia nervosa (AN) is a severe eating disorder affecting around 1 per 100 persons. However, the knowledge about its underlying pathophysiology is limited. To address the need for a better understanding of AN, an animal model was established early on in the late 1960's: the activity-based anorexia (ABA) model in which rats have access to a running wheel combined with restricted food access leading to self-starving/body weight loss and hyperactivity. Both symptoms, separately or combined, can also be found in patients with AN. The aim of this systematic review was to compile the current knowledge about this animal model as well as to address gaps in knowledge. Using the data bases of PubMed, Embase and Web of science 102 publications were identified meeting the search criteria. Here, we show that the ABA model mimics core features of human AN and has been characterized with regards to brain alterations, hormonal changes as well as adaptations of the immune system. Moreover, pharmacological interventions in ABA animals and new developments, such as a chronic adaptation of the ABA model, will be highlighted. The chronic model might be well suited to display AN characteristics but should be further characterized. Lastly, limitations of the model will be discussed.

Sows with increased blood glucose during late gestation may have decreased feed intake in lactation. Supplying dietary fibre to the sow reportedly modulates blood glucose and improves feed intake. The objective of this study was to evaluate the effects of dietary inclusion of cactus (Opuntia ficus-indica) on the regulation of blood glucose and productive performance in lactating sows. Data from 52 hybrid sows were analysed. The sows were divided into two groups, namely a control group (CG), that is, sows fed conventionally; and an experimental group (EG), that is, sows fed commercial feed plus cacti. Blood glucose in late gestation, and feed intake, milk production and milk quality, development of the piglet, energy balance, post-weaning body weight balance and the interval from weaning to oestrus were recorded. Preprandial blood glucose was 55.9 mg per dL in EG and 71.4 in CG. Sows on EG had greater daily feed intake and lower negative energy balance (5.4 kg/day and -2.8 MJ/day) than those on CG (4.5 kg/day and -9.4 MJ/day). Sows fed EG produced more milk (8.6 L/day) than those on CG (8.1 L/day). The quality of milk produced and the weaning weight of piglets were similar for the two groups. Body weight balance after weaning was greater for sows fed EG, 3.5% versus -1.5% in those fed CG. The weaning to oestrus interval was 0.6 days less for sows fed EG than those fed CG. Feeding cactus to lactating sows regulated blood glucose, which improved most of their productive indicators. [ABSTRACT FROM AUTHOR]

• Interleukin-1-saporin (IL1-SAP) killed neurons known to bear Interleukin-1 receptor. • Arcuate hypothalamus (ARH) neuropeptide Y neurons expressed Interleukin-1 receptor. • ARH IL1-SAP pretreatment attenuated subsequent systemic IL1-induced hypophagia. • ARH IL1-SAP pretreatment did not affect later peripheral LPS-induced hypophagia. A reduction in food intake is commonly observed after bacterial infection, a phenomenon that can be reproduced by peripheral administration of Gram-negative bacterial lipopolysaccharide (LPS) or interleukin-1beta (IL-1β), a pro-inflammatory cytokine released by LPS-activated macrophages. The arcuate nucleus of the hypothalamus (ARH) plays a major role in food intake regulation and expresses IL-1 type 1 receptor (IL-1R1) mRNA. In the present work, we tested the hypothesis that IL-1R1 expressing cells in the ARH mediate IL-1β and/or LPS-induced hypophagia in the rat. To do so, we developed an IL-1β-saporin conjugate, which eliminated IL-R1-expressing neurons in the hippocampus, and micro-injected it into the ARH prior to systemic IL-1β and LPS administration. ARH IL-1β-saporin injection resulted in loss of neuropeptide Y-containing cells and attenuated hypophagia and weight loss after intraperitoneal IL-1β, but not LPS, administration. In conclusion, the present study shows that ARH NPY-containing neurons express functional IL-1R1s that mediate peripheral IL-1β-, but not LPS-, induced hypophagia. Our present and previous findings indicate that the reduction of food intake after IL-1β and LPS are mediated by different neural pathways. [ABSTRACT FROM AUTHOR]

Abstract Despite generally being a reinforcing drug of abuse, amphetamine (amph) also produces effects such as hypophagia and conditioned taste avoidance (CTA), which may indicate that amph acts as an aversive homeostatic stressor. Stress-responsive prolactin-releasing peptide (PrRP)-positive noradrenergic and glucagon-like peptide-1 (GLP-1)-positive neurons in the caudal nucleus of the solitary tract (cNTS) are modulated by metabolic state, and are prime candidates for mediating amph-induced hypophagia and CTA. The present study used dual immunolabeling and fluorescent in situ hybridization (RNAscope) to examine acute amph-induced activation of cFos expression in phenotypically-identified cNTS neurons in ad lib-fed vs. overnight-fasted male Sprague Dawley rats. We also examined the impact of food deprivation on amph-induced CTA. Compared to control saline treatment, amph activated significantly more cNTS neurons, including PrRP-negative noradrenergic (NA) neurons, GABAergic neurons, and glutamatergic neurons, but not PrRP or GLP-1 neurons. Amph also increased neural activation within a subset of central cNTS projection targets, including the lateral parabrachial nucleus and central amygdala, but not the paraventricular hypothalamus. Food deprivation did not alter amph-induced neural activation or impact the ability of amph to support CTA. These findings indicate that PrRP-negative NA and other cNTS neurons are recruited by acute amph treatment regardless of metabolic state, and may participate in amph-induced hypophagia and CTA. Highlights • Amph activates noradrenergic, GABAergic, and glutamatergic cNTS neurons. • Amph does not activate GLP-1, PrRP, or CCK neurons in the cNTS. • Food deprivation does not alter the ability of amph to activate cNTS cFos, or to support CTA. [ABSTRACT FROM AUTHOR]

The effect of cactus (Opuntia ficus-indica) added to the diet of lactating (21 days of lactation) sows on voluntary feed intake, and its impact on the productive and reproductive post-weaning performance was evaluated. Data collected of 72 farrowings from 37 hybrid sows were analyzed during 12-month period. The sows were divided into two groups: (i) control group (CG; n = 18 sows), sows fed only with commercial feed, and (ii) experimental group (EG; n = 19 sows), sows fed with commercial feed plus cactus supplement. The variables evaluated were blood glucose (BG), daily feed intake (DFI) and total feed intake (TFI), loss of body weight (LBW), weaning-estrus interval (WEI), and subsequent litter size (SLS). Data analysis was carried out using fixed effects models. A nested effect was found for farrowing number (FN) into of group and an interaction group × season on the analyzed variables (P < 0.001). EG observed lower levels of BG with 47.0 ± 7.9 mg dL−1 pre-prandial and 56.1 ± 5.9 mg dL−1 post-prandial at the 10th day of lactation (P < 0.05). DFI and TFI were higher in the sows of the EG independently of the FN and season (P < 0.05). No differeces were observed on the nested effect of FN into group on the levels of BG (P < 0.05). Autumn showed the higher TFI: 121.4 kg−1 sow−1 (P < 0.05). Sows from CG 3rd farrowing and from EG 4th farrowing observed higher LBW (13.8 and 6.9%, respectively) (P < 0.05). Summer showed a higher LBW with 12.7% for CG and 8.2% for EG (P < 0.05). EG showed a lower WEI (5.5 days) and greater SLS up to 1.8 piglets more depending upon the season (P < 0.05). The lactating sow’s diet supplemented with cactus can counterbalance the negative effects of lactational hypophagia due to reduction on levels of BG during lactation and an increase on DFI and, therefore, improves performance of LBW, WEI, and SLS. [ABSTRACT FROM AUTHOR]

Background Visceral obesity is associated with diabetogenic and atherogenic abnormalities, including insulin resistance and increased risk for cardiometabolic diseases and mortality. Rodent lipectomy studies have demonstrated a causal link between visceral fat and insulin resistance, yet human omentectomy studies have failed to replicate this metabolic benefit, perhaps owing to the inability to target the mesentery. Objectives We aimed to demonstrate that safe and effective removal of mesenteric fat could be achieved in obese insulin-resistant baboons using tissue liquefaction technology. Setting Southwest National Primate Research Center, San Antonio, Texas. Methods Tissue liquefaction technology has been developed to enable mesenteric visceral lipectomy (MVL) to be safely performed without disturbing the integrity of surrounding nerves and vessels in the mesentary. After an initial MVL optimization study (n = 3), we then performed MVL (n = 4) or sham surgery (n = 2) in a cohort of insulin-resistant baboons, and the metabolic phenotype was assessed via hyperinsulinemic-euglycemic clamps at baseline and 6 weeks later. Results MVL led to a 75% improvement in glucose disposal at 6-weeks follow-up ( P = .01). Moreover, despite removing only an average of 430 g of mesenteric fat (~1% of total body mass), MVL led to a 14.4% reduction in total weight ( P = .001). Thus, these data demonstrate that mesenteric fat can be safely targeted for removal by tissue liquefaction technology in a nonhuman primate, leading to substantial metabolic improvements, including reversal of insulin resistance and weight loss. Conclusions These data provide the first demonstration of successful adipose tissue removal from the mesentery in a mammal. Importantly, we have demonstrated that when MVL is performed in obese, insulin-resistant baboons, insulin resistance is reversed, and significant weight loss occurs. Therefore, trials performing MVL in humans with abdominal obesity and related metabolic sequelae should be explored as a potential clinical tool to ameliorate insulin resistance and treat type 2 diabetes. [ABSTRACT FROM AUTHOR]

Abstract: Background and Aim: Peroxisome proliferator‐activated receptor alpha (PPARα) is a molecular target of various fibrate drugs clinically used to lower serum lipids. However, the tissue‐specific functions of PPARα remain to be elucidated. This study aimed to explore the tissue‐specific functions of PPARα in response to Wy‐14643. Methods: A hepatocyte‐specific Ppara knockout mouse line was used to explore the impact of hepatic PPARα activity on the systemic response to treatment with the potent PPARα agonist Wy‐14643. Results: Wy‐14643 mainly activated hepatic PPARα and regulated the expression of PPARα target genes in liver. Hepatic Ppara disruption abolished the triglyceride lowering effects of Wy‐14643, prevented agonist‐induced hypophagia, and ablated PPARα target gene response in the liver. Conclusions: These findings indicate that Wy‐14643 treatment mainly activates hepatic PPARα, and the hypolipidemic and hypophagic effects of Wy‐14643 are dependent on PPARα activation within hepatocytes. [ABSTRACT FROM AUTHOR]

Summary Transient reduced food intake (hypophagia) following high stress could have beneficial effects on longevity, but paradoxically, hypophagia can persist and become anorexia-like behavior. The neural underpinnings of stress-induced hypophagia and the mechanisms by which the brain prevents the transition from transient to persistent hypophagia remain undetermined. In this study, we report the involvement of a network governing goal-directed behavior (decision). This network consists of the ascending serotonergic inputs from the dorsal raphe nucleus (DR) to the medial prefrontal cortex (mPFC). Specifically, adult restoration of serotonin 4 receptor (5-HT 4 R) expression in the mPFC rescues hypophagia and specific molecular changes related to depression resistance in the DR (5-HT release elevation, 5-HT 1A receptor, and 5-HT transporter reductions) of stressed 5-HT 4 R knockout mice. The adult mPFC-5-HT 4 R knockdown mimics the null phenotypes. When mPFC-5-HT 4 Rs are overexpressed and DR-5-HT1ARs are blocked in the DR, hypophagia following stress persists, suggesting an antidepressant action of early anorexia. [ABSTRACT FROM AUTHOR]

The effect of spineless cactus intake ( Opuntia ficus-indica) on blood glucose (BG) levels in lactating sows and its impact on daily and total feed intake (dFI and TFI, respectively), body weight loss (BWL), and weaning-estrus interval length (WEI) were evaluated. Thirty-four hybrid (Yorkshire × Landrace × Pietrain) sows in lactation phase were used. Sows were divided into two groups: G1 ( n = 17) where they received commercial feed and G2 ( n = 17) provided with commercial feed plus an average of 2.0 ± 0.5 kg spineless cactus, based on a sow's body weight. The variables evaluated were BG, dFI, TFI, BWL, and WEI. Statistical analysis was performed by using a fixed and mixed model methodology, under a repeated measurements experiment. Group effects were found on all analyzed variables ( P < 0.05). The BG was lower in G2 (55.2 and 64.5 mg/dL pre- and post-prandial, respectively), compared to that in G1 (70.9 and 80.1 mg/dL pre- and post-prandial, respectively) ( P < 0.05). G2 showed better performance than G1 for dFI, BWL, and WEI ( P < 0.05) whose averages were 5.5 ± 1.8 kg, 7.4 ± 4.5%, and 5.3 ± 1.2 days, respectively. Averages for these variables in G1 were 4.7 ± 1.5 kg, 16.8 ± 4.6%, and 6.1 ± 1.6 days, respectively. Intake of spineless cactus reduced BG levels in lactating sows, generating greater dFI, lower BWL at the end of lactation, and a lower WEI. [ABSTRACT FROM AUTHOR]

• Orexin deficiency in mice did not affect binge-like eating in either sex. • Orexin deficiency increased body weight and post-binge hypophagia mainly in females. • Orexin deficiency increased post-binge stress levels selectively in females. • Male wild-type mice showed post-binge anxiety, but orexin-deficient mice did not. • These results emphasize the sexual dimorphism of the orexin system. Binge eating disorder is a debilitating disease characterized by recurrent episodes of excessive food consumption and associated with psychiatric comorbidities. Despite a growing body of research investigating the neurobiological underpinnings of eating disorders, specific treatments are lacking. Given its fundamental role in feeding behaviors, we investigated the role of the orexin (hypocretin) neuropeptide system in binge-like eating and associated phenotypes. Specifically, we submitted female and male orexin-deficient mice to a paradigm of intermittent access (once weekly for 24 h) to a Western diet (WD) to induce binge-like eating. Additionally, we measured their anxiety-like behavior and plasma corticosterone levels. All mice showed binge-like eating in response to the intermittent WD access, but females did so to a greater extent than males. While orexin deficiency did not affect binge-like eating in this paradigm, we found that female orexin-deficient mice generally weighed more, and they expressed increased hypophagia and stress levels compared to wild-type mice following binge-like eating episodes. These detrimental effects of orexin deficiency were marginal or absent in males. Moreover, male wild-type mice expressed post-binge anxiety, but orexin-deficient mice did not. In conclusion, these results extend our knowledge of orexin's role in dysregulated eating and associated negative affective states, and contribute to the growing body of evidence indicating a sexual dimorphism of the orexin system. Considering that many human disorders, and especially eating disorders, have a strong sex bias, our findings further emphasize the importance of testing both female and male subjects. [ABSTRACT FROM AUTHOR]

Histaminergic neurons in the hypothalamic tuberomamillary nucleus (TMN) establish connections with virtually all brain areas. Recent evidence suggests that feeding-related motivation is correlated with the activation of a subpopulation of histamine neurons in the ventral TMN that project to hypothalamic and subcortical areas controlling feeding behaviour. Oleoylethanolamide (OEA) is a hypophagic lipid-amide released by the small intestine in response to daily fat intake that indirectly activates hypothalamic oxytocin-neurons in the paraventricular (PVN) and supraoptic (SON) nuclei. We recently showed that OEA requires the integrity of neuronal histamine to fully display its hypophagic effect. Here we aimed to investigate if differences exist in OEA-induced c-Fos expression in several brain regions of fasted, histidine decarboxylase (HDC)-KO mice that do not synthesize histamine, and wild type (WT) littermates. All the brain regions examined receive histaminergic innervation and are involved in different aspects of feeding behaviour. We found that OEA increased c-Fos expression in the SON, arcuate nucleus (ARC) and the amygdala of WT mice, but not HDC-KO mice, whereas neither genotype nor treatment differences were observed in the lateral and dorsomedial hypothalamus. Furthermore, oxytocin-immunostaining was markedly increased in the neurohypophysis of WT and not in HDC-KO mice. Of note, OEA increased c-Fos expression in the nucleus of solitary tract of both genotypes. Our findings suggest that the TMN serves as a relay station to elaborate peripheral signals that control homeostatic and adaptive behavioural responses. [ABSTRACT FROM AUTHOR]

Polar bears (Ursus maritimus) have adapted to an annual cyclic regime of feeding and fasting, which is extreme in seasonal sea ice regions of the Arctic. As a consequence of climate change, sea ice breakup has become earlier and the duration of the openwater period through which polar bears must rely on fat reserves has increased. To date, there is limited empirical data with which to evaluate the potential energetic capacity of polar bears to withstand longer fasts.Wemeasured the incoming and outgoingmass of inactive polar bears (np142) that were temporarily detained by Manitoba Conservation and Water Stewardship during the open-water period near the town of Churchill, Manitoba, Canada, in 2009–2014. Polar bears were given access to water but not food and held for a median length of 17 d. Median mass loss rates were 1.0 kg/d, while median mass-specific loss rates were 0.5%/d, similar to other species with high adiposity and prolonged fasting capacities. Mass loss by unfed captive adult males was identical to that lost by free-ranging individuals, suggesting that terrestrial feeding contributes little to offsetmass loss. The inferred metabolic rate was comparable to a basal mammalian rate, suggesting that while on land, polar bears can maintain a depressed metabolic rate to conserve energy. Finally, we estimated time to starvation for subadults and adult males for the on-land period. Results suggest that at 180 d of fasting, 56%–63% of subadults and 18%–24% of adult males in this study would die of starvation Results corroborate previous assessments on the limits of polar bear capacity to withstand lengthening ice-free seasons and emphasize the greater sensitivity of subadults to changes in sea ice phenology. [ABSTRACT FROM AUTHOR]

We measured serum CORT elevation in wild-type and PACAP-deficient C57BL/6N male mice after acute (1 h) or prolonged (2–3 h) daily restraint stress for 7 d. The PACAP dependence of CORT elevation was compared to that of stress-induced hypophagia. Daily restraint induced unhabituated peak CORT elevation, and hypophagia/weight loss, of similar magnitude for 1, 2, and 3 h of daily restraint, in wild-type mice. Peak CORT elevation, and hypophagia, were both attenuated in PACAP-deficient mice for 2 and 3 h daily restraint. Hypophagia induced by 1-h daily restraint was also greatly reduced in PACAP-deficient mice, however CORT elevation, both peak and during recovery from stress, was unaffected. Thus, hypothalamic PACAPergic neurotransmission appears to affect CRH gene transcription and peptide production, but not CRH release, in response to psychogenic stress. A single exposure to restraint sufficed to trigger hypophagia over the following 24 h. PACAP deficiency attenuated HPA axis response (CORT elevation) to prolonged (3 h) but not acute (1 h) single-exposure restraint stress, while hypophagia induced by either a single 1 h or a single 3 h restraint were both abolished in PACAP-deficient mice. These results suggest that PACAP’s actions to promote suppression of food intake following an episode of psychogenic stress is unrelated to the release of CRH into the portal circulation to activate the pituitary-adrenal axis. Furthermore, demonstration of suppressed food intake after a single 1-h restraint stress provides a convenient assay for investigating the location of the synapses and circuits mediating the effects of PACAP on the behavioral sequelae of psychogenic stress. [ABSTRACT FROM PUBLISHER]

Background: The neuropeptide PACAP (pituitary adenylate cyclase-activating polypeptide) is a master regulator of central and peripheral stress responses, yet it is not clear how PACAP projections throughout the brain execute endocrine and behavioral stress responses., Methods: We used AAV (adeno-associated virus) neuronal tracing, an acute restraint stress (ARS) paradigm, and intersectional genetics, in C57BL/6 mice, to identify PACAP-containing circuits controlling stress-induced behavior and endocrine activation., Results: PACAP deletion from forebrain excitatory neurons, including a projection directly from medial prefrontal cortex to hypothalamus, impairs c-fos activation and corticotropin-releasing hormone (CRH) messenger RNA elevation in the paraventricular nucleus after 2 hours of restraint, without affecting ARS-induced hypophagia, or c-fos elevation in nonhypothalamic brain. Elimination of PACAP within projections from lateral parabrachial nucleus to extended amygdala, on the other hand, attenuates ARS-induced hypophagia, along with extended amygdala fos induction, without affecting ARS-induced CRH messenger RNA elevation in the paraventricular nucleus. PACAP projections to extended amygdala terminate at protein kinase C delta type (PKCδ) neurons in both the central amygdala and the oval bed nucleus of the stria terminalis. Silencing of PKCδ neurons in the central amygdala, but not in the oval bed nucleus of the stria terminalis, attenuates ARS-induced hypophagia. Experiments were carried out in mice of both sexes with n ≥ 3 per group., Conclusions: A frontocortical descending PACAP projection controls paraventricular nucleus CRH messenger RNA production to maintain hypothalamic-pituitary-adrenal axis activation and regulate the endocrine response to stress. An ascending PACAPergic projection from the external lateral parabrachial nucleus to PKCδ neurons in the central amygdala regulates behavioral responses to stress. Defining two separate limbs of the acute stress response provides broader insight into the specific brain circuitry engaged by the psychogenic stress response., (© 2023 Published by Elsevier Inc on behalf of Society of Biological Psychiatry.)

Background: Taking examinations is central to student experience at University and may cause psychological stress. Although stress is recognised to impact on food intake, the effects of undertaking examinations on students' dietary intake have not been well characterised. The purpose of this study was to assess how students' energy and nutrient intake may alter during examination periods.Methods: The study design was a within-subject comparison of students' energy and nutrient intake during an examination period contrasted with that outside an examination period (baseline). A total of 20 male students from the University of Sheffield completed an automated photographic 4-d dietary record alongside four 24-h recalls in each time period. Daily energy and nutrient intake was estimated for each student by time period and change in energy and nutrient intake calculated. Intakes at baseline were compared to UK dietary recommendations. Cluster analysis categorised students according to their change in energy intake between baseline and the examination period. Non-parametric statistical tests identified differences by cluster.Results: Baseline intakes did not meet recommendations for energy, non-milk extrinsic sugars, non-starch polysaccharide and sodium. Three defined clusters of students were identified: Cluster D who decreased daily energy intake by 12.06 MJ (n = 5), Cluster S who had similar energy intakes (n = 13) and Cluster I who substantially increased energy intake by 6.37 MJ (n = 2) between baseline and examination period. There were statistically significant differences (all p < 0.05) in change in intake of protein, carbohydrate, calcium and sodium between clusters. Cluster D recorded greater energy, carbohydrate and protein intakes than Cluster I at baseline.Conclusions: The majority of students were dietary resilient. Students who demonstrated hypophagia in the examination period had a high energy and nutrient intake at baseline, conversely those who showed hyperphagia had a low energy and nutrient intake. These patterns require confirmation in studies including women, but if confirmed, there is need to address some students' poor food choice especially during examinations. [ABSTRACT FROM AUTHOR]

Previous reports indicate that caloric restriction attenuates anxiety and other behavioral responses to acute stress, and blunts the ability of stress to increase anterior pituitary release of adrenocorticotropic hormone. Since hindbrain glucagon-like peptide-1 (GLP-1) neurons and noradrenergic prolactin-releasing peptide (PrRP) neurons participate in behavioral and endocrine stress responses, and are sensitive to the metabolic state, we examined whether overnight food deprivation blunts stress-induced recruitment of these neurons and their downstream hypothalamic and limbic forebrain targets. A single overnight fast reduced anxiety-like behavior assessed in the elevated-plus maze and acoustic startle test, including marked attenuation of light-enhanced startle. Acute stress [i.e., 30 min restraint (RES) or 5 min elevated platform exposure] robustly activated c-Fos in GLP-1 and PrRP neurons in fed rats, but not in fasted rats. Fasting also significantly blunted the ability of acute stress to activate c-Fos expression within the anterior ventrolateral bed nucleus of the stria terminalis (vlBST). Acute RES stress suppressed dark-onset food intake in rats that were fed ad libitum, whereas central infusion of a GLP-1 receptor antagonist blocked RES-induced hypophagia, and reduced the ability of RES to activate PrRP and anterior vlBST neurons in ad libitum-fed rats. Thus, an overnight fast "silences" GLP-1 and PrRP neurons, and reduces both anxiety-like and hypophagic responses to acute stress. The partial mimicking of these fasting-induced effects in ad libitum-fed rats after GLP-1 receptor antagonism suggests a potential mechanism by which short-term negative energy balance attenuates neuroendocrine and behavioral responses to acute stress. [ABSTRACT FROM AUTHOR]

Prior to hibernation, 13-lined ground squirrels ( Ictidomys tridecemlineatus) enter a hypophagic period where food consumption drops by an average of 55% in 3 weeks. This occurs naturally, while the ground squirrels are in constant environmental conditions and have free access to food. Importantly, this transition occurs before exposure to hibernation conditions (5°C and constant darkness), so the ground squirrels are still maintaining a moderate level of activity. In this study, we used the Illumina HiSeq 2000 system to sequence the hypothalamic transcriptomes of ground squirrels before and after the autumn feeding transition to examine the genes underlying this extreme change in feeding behavior. The hypothalamus was chosen because it is known to play a role in the control and regulation of food intake and satiety. Overall, our analysis identified 143 genes that are significantly differentially expressed between the two groups. Specifically, we found five genes associated with feeding behavior and obesity ( VGF, TRH, LEPR, ADIPOR2, IRS2) that are all upregulated during the hypophagic period, after the feeding transition has occurred. We also found that serum leptin significantly increases in the hypophagic group. Several of the genes associated with the natural autumnal feeding decline in 13-lined ground squirrels show parallels to signaling pathways known to be disrupted in human metabolic diseases, like obesity and diabetes. In addition, many other genes were identified that could be important for the control of food consumption in other animals, including humans. [ABSTRACT FROM AUTHOR]

Many cytokines have been proposed to regulate reproduction due to their actions on hypothalamic kisspeptin cells, the main modulators of gonadotropin-releasing hormone (GnRH) neurons. Hormones such as leptin, prolactin and growth hormone are good examples of cytokines that lead to Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway activation, consequently exerting effects in kisspeptin neurons. Different studies have investigated how specific components of the JAK/STAT signaling pathway affect the functions of kisspeptin cells, but the role of the suppressor of cytokine signaling 3 (SOCS3) in mediating cytokine actions in kisspeptin cells remains unknown. Cre-Loxp technology was used in the present study to ablate Socs3 expression in kisspeptin cells (Kiss1/Socs3 -KO). Then, male and female control and Kiss1/Socs3 -KO mice were evaluated for sexual maturation, energy homeostasis features, and fertility. It was found that hypothalamic Kiss1 mRNA expression is significantly downregulated in Kiss1/Socs3 -KO mice. Despite reduced hypothalamic Kiss1 mRNA content, these mice did not present any sexual maturation or fertility impairments. Additionally, body weight gain, leptin sensitivity and glucose homeostasis were similar to control mice. Interestingly, Kiss1/Socs3 -KO mice were partially protected against lipopolysaccharide (LPS)-induced body weight loss. Our results suggest that Socs3 ablation in kisspeptin cells partially prevents the sickness behavior induced by LPS, suggesting that kisspeptin cells can modulate energy metabolism in mice in certain situations. [ABSTRACT FROM AUTHOR]

• Early-life stress exposure does not influence conditioned taste aversion learning in adult male rats. • Adolescent fluoxetine exposure does not influence conditioned taste aversion learning in adult male or female rats. • Adolescent fluoxetine exposure mediates a long-term decrease in body weight-gain in male, but not female, Sprague-Dawley rats. In rodents, early-life exposure to environmental stress or antidepressant medication treatment has been shown to induce similar long-term consequences on memory- and depression-related behavior in adulthood. To expand on this line of work, we evaluated how juvenile exposure to chronic variable stress (CVS) or the selective serotonin reuptake inhibitor fluoxetine (FLX) influences conditioned taste aversion (CTA) learning in adulthood. To do this, in Experiment 1, we examined how adolescent CVS alone (postnatal day [PND] 35–48), or with prenatal stress (PNS) history (PNS + CVS), influenced the acquisition and extinction of CTA in adult male Sprague Dawley rats. Specifically, at PND70+ (adulthood), rats were presented with 0.15 % saccharin followed by an intraperitoneal (i.p.) injection of lithium chloride (LiCl) to induce visceral malaise. A total of four saccharin (conditioned stimulus) and LiCl (unconditioned stimulus) pairings occurred across the CTA acquisition phase. Next, saccharin was presented without aversive consequences, and intake was measured across consecutive days of the extinction phase. No differences in body weight gain across the experimental days, rate of CTA acquisition, or extinction of CTA, were observed among the experimental groups (control, n = 7; CVS, n = 12; PNS + CVS, n = 9). In Experiment 2, we evaluated if early-life FLX exposure alters CTA learning in adulthood. Specifically, adolescent stress naïve male and female rats received FLX (0 or 20 mg/kg/i.p) once daily for 15 consecutive days (PND35-49). During antidepressant exposure, FLX decreased body weight gain in both male (n = 7) and female rats (n = 7), when compared to respective controls (male control, n = 8; female control, n = 8). However, juvenile FLX exposure decreased body weight-gain in adult male, but not female, rats. Lastly, adolescent FLX history had no effect on CTA acquisition or extinction in adulthood (PND70), in neither male nor female rats. Together, the data indicate that juvenile FLX exposure results in a long-term decrease of body weight-gain in a male-specific manner. Yet, independent of sex, neither early-life stress nor FLX exposure alters CTA learning in adulthood. [ABSTRACT FROM AUTHOR]

Background: Patients with gastrointestinal or lung cancer often suffer from a loss of appetite (anorexia), resulting in reduced food intake (hypophagia) and body weight loss. This study evaluated the prevalence of anorexia, hypophagia, pre-cachexia and cachexia in patients with cancer at time of diagnosis., Patients and Methods: Patients with newly diagnosed gastrointestinal or lung cancers were included. Body mass index (BMI) and weight loss over the prior 6 months were recorded. Patients were assessed for (pre-)cachexia and for anorexia using the Functional Assessment of Anorexia/Cachexia Therapy (FAACT) and a specific anorexia questionnaire (AQ). Energy and protein intake were calculated through food diaries. Patients were considered hypophagic if intake was ≤70% of guideline-recommended levels., Results: Overall, 102 patients [53 male; median age: 67 (range, 21-88) years] were enrolled. Mean BMI (± standard deviation) was 23.1 ± 3.4 kg/m 2 ; average percentage of weight loss was 10.1 ± 7.8%. At diagnosis, 68% (69/102) of patients had cachexia, and 11% (11/102) pre-cachexia. Prevalence of anorexia was 57% (58/102) and 75% (76/102) according to FAACT and AQ, respectively. Forty-eight percent (49/102) of patients had hypophagia. Patients with anorexia had lower daily energy ( p = 0.002) and protein intake ( p = 0.0257), and greater percentage of weight loss ( p = 0.0005). In patients with hypophagia, negative correlations were observed between percentage of weight loss and total daily calorie (r = -0.40; p = 0.01) and protein intake (r = -0.340; p = 0.018)., Conclusion: Anorexia, inadequate nutritional intake and cachexia are highly prevalent in patients with gastrointestinal or lung cancer at diagnosis. Negative protein and energy balance may play an important role in the pathogenesis of cachexia. Early multimodal strategies to improve food intake are urgently needed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Molfino, Emerenziani, Tonini, Santini, Gigante, Guarino, Nuglio, Imbimbo, La Cesa, Cicala and Muscaritoli.)

Propionic acid is more hypophagic for cows with elevated hepatic acetyl coenzyme A (CoA) concentration in the postpartum period. The objective of this experiment was to evaluate the interaction of hepatic acetyl CoA concentration, which is elevated by intravenous lipid infusion, and intraruminal propionic acid infusion on feed intake and feeding behavior responses of lactating cows. Eight multiparous, ruminally cannulated, Holstein dairy cows past peak lactation were used in a replicated 4 x 4 Latin square experiment with a 2 x 2 factorial arrangement of treatments. Treatments were propionic acid (PI) infused intraruminally at 0.5 mol/h for 18 h starting 6 h before feeding and behavior monitoring or sham control (CO), and intravenous jugular infusion of lipid (LI, Intralipid 20%; Baxter US, Deerfield, IL) or saline (SI, 0.9% NaCl; Baxter US) infused at 250 mL/h for 12 h before feeding and behavior monitoring, and then 500 mL/h for 12 h after feeding. Changes in plasma concentrations of metabolites and hormones and hepatic acetyl CoA from before infusion until the end of infusion were evaluated. We observed a tendency for an interaction between PI and LI for the change in plasma nonesterified fatty acid (NEFA) concentration from the preliminary day to the end of the infusion period. Infusion of propionic acid decreased dry matter intake (DMI) 15% compared with CO, but lipid infusion did not affect DMI over the 12 h following feeding. Infusion of propionic acid tended to decrease hepatic acetyl CoA concentration from the preliminary day to the end of the infusion compared with CO, consistent with PI decreasing DMI by stimulating oxidation of acetyl CoA. Contrary to our expectations, LI did not increase concentration of NEFA or β-hydroxybutyrate in plasma, concentration of acetyl CoA in the liver, or milk fat yield, suggesting that the infused lipid was stored or oxidized by extrahepatic tissues. As a result, we detected no interaction between PI and LI for DMI. Although the effect of PI on DMI was consistent with our previous results, this lipid infusion model using cows past peak lactation was not useful to simulate the lipolytic state of cows in the postpartum period in this experiment. [ABSTRACT FROM AUTHOR]