Search

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.)

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.

• 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]

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.)

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.)