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OBJECTIVE: Obesity is linked to perturbations in energy balance mechanisms, including ghrelin and leptin actions at the hypothalamic circuitry of neuropeptide Y (NPY) and melanocortin. However, information about the regulation of this system in the periphery is still scarce. Our objective was to study the regulation of the NPY/melanocortin system in the adipose tissue (AT) and evaluate its therapeutic potential for obesity and type 2 diabetes. METHODS: The expression of the NPY/melanocortin receptors' levels was assessed in the visceral AT of individuals with obesity and altered metabolism. Protein levels of these receptors were evaluated in cultured adipocytes incubated with ghrelin (30 and 100 ng/mL) and leptin (1 and 10 nM) and in the AT of an animal model with a mutation in the leptin receptor (ZSF1 rat), to understand their regulation by leptin and ghrelin. The vertical sleeve gastrectomy animal model was used to evaluate the putative therapeutic potential of the NPY/melanocortin system. RESULTS: In this study, we unravelled that leptin (1 nM and 10 nM) selectively reduced the levels of NPY5R and MC3R but no other NPYR/MCRs in cultured adipocytes. In turn, acylated ghrelin (100ng/mL) significantly increased NPY1R, but the inhibition of its receptor also abrogates MC3R levels. However, in the Lepr-deficient ZSF1 rat, both NPY5R and MC3R levels were reduced, along with other NPYRs and MCRs, suggesting that leptin resistance negatively affects NPY and melanocortin signalling. In human adipose tissue, we found a downregulation of genes encoding the NPY and melanocortin receptors in the visceral AT of individuals with obesity and insulin resistance, being correlated with genes regulating metabolic activity. Additionally, diabetic obese rats submitted to vertical sleeve gastrectomy showed increased levels of NPY, melanocortin, ghrelin, and leptin receptors in the AT, including MC3R, suggesting it may constitute a therapeutic target in obesity. CONCLUSIONS: Our results suggest that the AT NPY/melanocortin system, particularly the MC3R, may be involved in the neuroendocrine regulation of adipocyte metabolism. Altogether, our work shows MC3R is under the control of the ghrelin/leptin duo, is reduced in patients with obesity and prediabetes, and may constitute a therapeutic target in obesity.

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Evidence suggests that fish are more tolerant than mammals to imbalanced dietary amino acid profiles. However, the behavioral and physiological responses of fish to individual deficiencies in dietary indispensable amino acids (IDAA) remain unclear. This study examined how stomachless fish respond to diets deficient in limiting IDAA (lysine, methionine, and threonine), using Zebrafish (Danio rerio) as a model. The response to deficient diets was assessed based on; 1) growth performance and feeding efficiency; 2) feed intake; 3) expression of appetite-regulating hormones and nutrient-sensing receptors; and 4) muscle postprandial free amino acid (FAA) levels. There were 6 treatments, each with 3 replicate tanks. A semi-purified diet was formulated for each group. The CG diet was based on casein and gelatin, while the FAA50 diet had 50 % of dietary protein supplied with crystalline amino acids. Both were formulated to contain matching, balanced amino acid profiles. The remaining diets were formulated the same as the FAA50 diet, with minor adjustments to create deficiencies in selected IDAA. The (-) Lys, (-) Met, and (-) Thr diets had lysine, methionine, and threonine withheld from the FAA mix, respectively, and the Def diet was deficient in all three. The juvenile Zebrafish were fed to satiation 3 times daily from 21 to 50 days-post-hatch. Results showed that 50 % replacement of dietary protein with crystalline amino acids significantly reduced growth of juvenile Zebrafish. There were no significant differences in growth between the FAA50 group and groups that received deficient diets. The deficiency of singular IDAA did not induce significant changes in feed intake; however, the combined deficiency in the Def diet caused a significant increase in feed intake. This increased feed intake led to decreased feeding efficiency. A significant decrease in feeding efficiency was also observed in the (-) Lys group. There was an observed upregulation of neuropeptide Y (NPY), an orexigenic hormone, in the Def group. Overall, results from this study suggest stomachless fish increase feed intake when challenged with IDAA-deficient diets, and the regulation of NPY might play a role in this response.

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AIMS: To investigate tear neuropeptide Y (NPY) and substance P concentrations in individuals with type 1 diabetes, comparing those with and without both diabetic retinopathy (DR) and peripheral neuropathy. METHODS: This cross-sectional study involved 41 participants with type 1 diabetes and none to moderate DR, and 22 healthy controls. Assessments included clinical ocular surface parameters, quantification of corneal nerve attributes (based on in vivo confocal microscopy imaging), DR grading, and evaluation for small and large fibre neuropathy. Concentrations of NPY and substance P in tear samples were measured using enzyme-linked immunosorbent assay. RESULTS: Mean (± standard deviation) tear NPY concentrations in participants with type 1 diabetes and length-dependent small fibre neuropathy (SFN) was lower than in controls (10.84 ± 4.10 ng/mL vs 14.72 ± 3.12 ng/mL; p=0.004), but not significantly different from type 1 diabetes participants without SFN (13.39 ± 4.66 ng/mL; p=0.11). Tear NPY levels were lower in individuals with type 1 diabetes and mild/moderate non-proliferative DR (10.44 ± 3.46 ng/mL) compared to none/minimal DR (13.79 ± 4.76 ng/mL; p=0.0005) and controls. In separate linear regression models, both the presence of SFN (ß = -0.75, p=0.02) and the presence of mild/moderate DR (ß = -0.84, p=0.009) were significantly associated with tear NPY levels relative to controls, after adjusting for participant age, sex, and dry eye disease. There were no inter-group differences for tear substance P concentrations. CONCLUSIONS: Tear NPY has potential utility as an indicator of peripheral microvascular complications associated with type 1 diabetes.

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High ambient temperatures (HT) can increase diencephalic neuropeptide Y (NPY) expression, and central injection of NPY attenuates heat stress responses while inducing an antioxidative state in the chick spleen. However, there is a lack of knowledge about NPY receptor expression, and its regulation by HT, in the chick spleen. In the current study, male chicks were used to measure the expression of NPY receptors in the spleen and other immune organs under acute (30 vs. 40 ± 1°C for 3 h) or chronic (30 vs. 40 ± 1°C for 3 h/day for 3 days) exposure to HT and in response to central injection of NPY (47 pmol, 188 pmol, or 1 nmol). We found that NPY-Y4 receptor mRNA was expressed in the spleen, but not in other immune organs studied. Immunofluorescence staining revealed that NPY-Y4 receptors were localized in the splenic pulp. Furthermore, NPY-Y4 receptor mRNA increased in the chick spleen under both acute and chronic exposure to HT. Central NPY at two dose levels (47 and 188 pmol) and a higher dose (1 nmol) did not increase splenic NPY-Y4 receptor mRNA expression or splenic epinephrine under HT (35 ± 1°C), and significantly increased 3-methoxy-4-hydroxyphenylglycol (MHPG) concentrations under HT (40 ± 1°C). In conclusion, increased expression of NPY-Y4 receptor mRNA in the spleen under HT suggest that Y4 receptor may play physiological roles in response to HT in male chicks.

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Maternal separation can have long-lasting effects on an individual's susceptibility to stress later in life. Maternal separation during the postnatal period is a commonly used paradigm in rodents to investigate the effects of early life stress on neurobehavioural changes and stress responsiveness. However, maternal separation during stress hyporesponsive and responsive periods of postnatal development may differ in its effects on stress resilience. Therefore, we hypothesised that late maternal separation (LMS) from postnatal day 10 to 21 in mice may have different effect on resilience than early maternal separation during the first week of postnatal life. Our results suggested that male LMS mice are more resilient to chronic variable stress (CVS)-induced anxiety and depressive-like behaviour as confirmed by the open field, light-dark field, elevated plus maze, sucrose preference and tail suspension tests. In contrast, female LMS mice were equally resilient as non-LMS female mice. We found increased expression of NPY, NPY1R, NPY2R, NPFFR1, and NPFFR2 in the hypothalamus of male LMS mice whereas the opposite effect was observed in the hippocampus. LMS in male and female mice did not affect circulating corticosterone levels in response to psychological or physiological stressors. Thus, LMS renders male mice resilient to CVS-induced neurobehavioural disorders in adulthood.

Sexual dimorphism exists in the effects of late maternal separation (LMS)LMS provides resilience to stress-induced anxiety and depression in male miceLMS upregulates NPY and NPVF system in the hypothalamus of male miceNo effect of LMS on stress-induced corticosterone levels.

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The Neuropeptide Y/RFamide-like receptors belong to the Rhodopsin-like G protein-coupled receptors G protein-coupled receptors (GPCRs) and are involved in functions such as locomotion, feeding and reproduction. With 41 described receptors they form the best-studied group of neuropeptide GPCRs in Caenorhabditis elegans. In order to understand the expansion of the Neuropeptide Y/RFamide-like receptor family in nematodes, we started from the sequences of selected receptor paralogs in C. elegans as query and surveyed the corresponding orthologous sequences in another 159 representative nematode target genomes. To this end we employed a automated pipeline based on ExonMatchSolver, a tool that solves the paralog-to-contig assignment problem. Utilizing subclass-specific HMMs we were able to detect a total of 1557 Neuropeptide Y/RFamide-like receptor sequences (1100 NPRs, 375 FRPRs and 82 C09F12.3) in the 159 target nematode genomes investigated here. These sequences demonstrate a good conservation of the Neuropeptide Y/RFamide-like receptors across the Nematoda and highlight the diversification of the family in nematode evolution. No other genus shares all Neuropeptide Y/RFamide-like receptors with the genus Caenorhabditis. At the same time, we observe large numbers of clade specific duplications and losses of family members across the phylum Nematoda.

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Neuropeptide Y (NPY), an endogenous peptide composed of 36 amino acids, has been investigated as a potential therapeutic agent for neurodegenerative diseases due to its neuroprotective attributes. This study investigated the neuroprotective effects of NPY in a mouse model of glaucoma characterized by elevated intraocular pressure (IOP) and progressive retinal ganglion cell degeneration. Elevated IOP in mice was induced through intracameral microbead injections, accompanied by intravitreal administration of NPY peptide. The results demonstrated that NPY treatment preserved both the structural and functional integrity of the inner retina and mitigated axonal damage and degenerative changes in the optic nerve under high IOP conditions. Further, NPY treatment effectively reduced inflammatory glial cell activation, as evidenced by decreased expression of glial fibrillary acidic protein and Iba-1. Notably, endogenous NPY expression and its receptors (NPY-Y1R and NPY-Y4R) levels were negatively affected in the retina under elevated IOP conditions. NPY treatment restored these changes to a significant extent. Molecular analysis revealed that NPY mediates its protective effects through the mitogen-activated protein kinase (MAPK) and PI3K/Akt signaling pathways. These findings highlight the therapeutic potential of NPY in glaucoma treatment, underscoring its capacity to preserve retinal health, modulate receptor expression under stress, reduce neuroinflammation, and impart protection against axonal impairment.

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Neuropeptide Y (NPY) is a 36-amino acid peptide that is widely expressed throughout the limbic system. Recent evidence has highlighted NPY as a marker of resilience to posttraumatic psychopathology, which may be due to its association with neural regions involved with emotion regulation. This study examined whether plasma NPY levels moderated the relationship between emotion regulation and psychopathology in a sample of adult survivors of childhood interpersonal trauma, a population known to be at high risk for psychopathology. Adults exposed to an interpersonal criterion A trauma during childhood (N = 54) were recruited from an urban population at a midwestern medical center and completed a baseline study visit as part of a larger clinical trial. Participants gave a blood sample in order to assess circulating levels of NPY and answered questions related to emotion regulation and mood-related pathology. Results of a moderated multiple regression showed that the overall model was significant R2 = 0.26, F (5, 48) = 3.46, p < .01. Difficulties in emotion regulation was significantly predictive of psychopathology (unstandardized B = 0.032, p < .01), and this relationship was significantly moderated by levels of NPY (unstandardized B = -0.001, p < .05) such that the relationship between emotion regulation and psychopathology was weaker for those with higher levels of NPY. Results suggest that higher levels of NPY may lessen the association between emotion regulation and posttraumatic psychopathology in survivors of childhood interpersonal trauma. Further investigation of the contribution of NPY to psychopathology in this population is warranted. NCT: 02279290.

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Growing evidence suggests that neuropeptide signaling shapes auditory computations. We previously showed that neuropeptide Y (NPY) is expressed in the inferior colliculus (IC) by a population of GABAergic stellate neurons and that NPY regulates the strength of local excitatory circuits in the IC. NPY neurons were initially characterized using the NPY-hrGFP mouse, in which humanized renilla green fluorescent protein (hrGFP) expression indicates NPY expression at the time of assay, i.e., an expression-tracking approach. However, studies in other brain regions have shown that NPY expression can vary based on several factors, suggesting that the NPY-hrGFP mouse might miss NPY neurons not expressing NPY on the experiment date. Here, we hypothesized that neurons with the ability to express NPY represent a larger population of IC GABAergic neurons than previously reported. To test this hypothesis, we used a lineage-tracing approach to irreversibly tag neurons that expressed NPY at any point prior to the experiment date. We then compared the physiological and anatomical features of neurons labeled with this lineage-tracing approach to our prior data set, revealing a larger population of NPY neurons than previously found. In addition, we used optogenetics to test the local connectivity of NPY neurons and found that NPY neurons provide inhibitory synaptic input to other neurons in the ipsilateral IC. Together, our data expand the definition of NPY neurons in the IC, suggest that NPY expression might be dynamically regulated in the IC, and provide functional evidence that NPY neurons form local inhibitory circuits in the IC.NEW & NOTEWORTHY Across brain regions, neuropeptide Y (NPY) expression is dynamic and influenced by extrinsic and intrinsic factors. We previously showed that NPY is expressed by a class of inhibitory neurons in the auditory midbrain. Here, we find that this neuron class also includes neurons that previously expressed NPY, suggesting that NPY expression is dynamically regulated in the auditory midbrain. We also provide functional evidence that NPY neurons contribute to local inhibitory circuits in the auditory midbrain.

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Neuropeptide Y receptor Y8 (NPY8R) is a fish-specific receptor with two subtypes, NPY8AR and NPY8BR. Changes in expression levels during physiological processes or in vivo regulation after ventricular injection suggest that NPY8BR plays an important role in feeding regulation; this has been found in only a few fish, at present. In order to better understand the physiological function of npy8br, especially in digestion, we used clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) technology to generate npy8br-/- Japanese medaka (Oryzias latipes). We found that the deletion of npy8br in medaka larvae affected their feeding and digestion ability, ultimately affecting their growth. Specifically, npy8br deficiency in medaka larvae resulted in decreased feed intake and decreased expression levels of orexigenic genes (npy and agrp). npy8br-/- medaka larvae fed for 10 d (10th day of feeding) still had incompletely digested brine shrimp (Artemia nauplii) in the digestive tract 8 h after feeding, the messenger RNA (mRNA) expression levels of digestion-related genes (amy, lpl, ctra, and ctrb) were significantly decreased, and the activity of amylase, trypsin, and lipase also significantly decreased. The deletion of npy8br in medaka larvae inhibited the growth and significantly decreased the expression of growth-related genes (gh and igf1). Hematoxylin and eosin (H&E) sections of intestinal tissue showed that npy8br-/- medaka larvae had damaged intestine, thinned intestinal wall, and shortened intestinal villi. So far, this is the first npy8br gene knockout model established in fish and the first demonstration that npy8br plays an important role in digestion.

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

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Osteoarthritis is a highly prevalent progressive joint disease that still requires an optimal therapeutic approach. Intermittent fasting is an attractive dieting strategy for improving health. Here this study shows that intermittent fasting potently relieves medial meniscus (DMM)- or natural aging-induced osteoarthritic phenotypes. Osteocytes, the most abundant bone cells, secrete excess neuropeptide Y (NPY) during osteoarthritis, and this alteration can be altered by intermittent fasting. Both NPY and the NPY-abundant culture medium of osteocytes (OCY-CM) from osteoarthritic mice possess pro-inflammatory, pro-osteoclastic, and pro-neurite outgrowth effects, while OCY-CM from the intermittent fasting-treated osteoarthritic mice fails to induce significant stimulatory effects on inflammation, osteoclast formation, and neurite outgrowth. Depletion of osteocyte NPY significantly attenuates DMM-induced osteoarthritis and abolishes the benefits of intermittent fasting on osteoarthritis. This study suggests that osteocyte NPY is a key contributing factor in the pathogenesis of osteoarthritis and intermittent fasting represents a promising nonpharmacological antiosteoarthritis method by targeting osteocyte NPY.

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In this analysis, we aimed to investigate the effect of COVID-19 disease on eating behavior. A total of 55 right-handed adults, <50 years of age, without overweight or obesity, from two cross-sectional studies were included. The first one enrolled subjects between September 2018 and December 2019 (non-COVID-19 group). The second one included subjects enrolled between March 2022 and May 2023; for this analysis, 28 with a history of COVID-19 (COVID-19 group) were retained. Hunger, TFEQ-18, plasma ghrelin, neuropeptide Y (NPY) and resting-state fMRI were assessed during fasting. Intraregional neuronal synchronicity and connectivity were assessed by voxel-based regional homogeneity (ReHo) and degree of centrality (DC). Significantly higher ghrelin and NPY levels were observed in the COVID-19 group than in the non-COVID-19 group (ghrelin 197.5 pg/mL vs. 67.1 pg/mL, p < 0.001; NPY 128.0 pg/mL vs. 84.5 pg/mL, p = 0.005). The NPY levels positively correlated with the DC and ReHo in the left lingual (r = 0.67785 and r = 0.73604, respectively). Similar scores were noted for cognitive restraint, uncontrolled eating and emotional eating in both groups according to the TFEQ-18 questionnaire results (p > 0.05 for all). Our data showed increased levels of appetite-related hormones, correlated with activity in brain regions involved in appetite regulation, persisting long after COVID-19 infection.

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Observed and recorded in various forms since ancient times, 'syncope' is often popularly called 'fainting', such that the two terms are used synonymously. Syncope/fainting can be caused by a variety of conditions, including but not limited to head injuries, vertigo, and oxygen deficiency. Here, we draw on a large body of literature on syncope, including the role of a recently discovered set of specialized mammalian neurons. Although the etiology of syncope still remains a mystery, we have attempted to provide a comprehensive account of what is known and what still needs to be performed. Much of our understanding of syncope is owing to studies in the laboratory mouse, whereas evidence from human patients remains scarce. Interestingly, the cardioinhibitory Bezold-Jarisch reflex, recognized in the early 1900s, has an intriguing similarity to-and forms the basis of-syncope. In this review, we have integrated this minimal model into the modern view of the brain-neuron-heart signaling loop of syncope, to which several signaling events contribute. Molecular signaling is our major focus here, presented in terms of a normal heart, and thus, syncope due to abnormal or weak heart activity is not discussed in detail. In addition, we have offered possible directions for clinical intervention based on this model. Overall, this article is expected to generate interest in chronic vertigo and syncope/fainting, an enigmatic condition that affects most humans at some point in life; it is also hoped that this may lead to a mechanism-based clinical intervention in the future.

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BACKGROUND: Apoprotein A-I (ApoA-I) and Apoprotein B (ApoB) have emerged as novel cardiovascular risk biomarkers influenced by feeding behavior. Hypothalamic appetite peptides regulate feeding behavior and impact lipoprotein levels, which effects vary in different weight states. This study explores the intricate relationship between body mass index (BMI), hypothalamic appetite peptides, and apolipoproteins with emphasis on the moderating role of body weight in the association between neuropeptide Y (NPY), ghrelin, orexin A (OXA), oxytocin in cerebrospinal fluid (CSF) and peripheral ApoA-I and ApoB. METHODS: In this cross-sectional study, we included participants with a mean age of 31.77 ± 10.25 years, categorized into a normal weight (NW) (n = 73) and an overweight/obese (OW/OB) (n = 117) group based on BMI. NPY, ghrelin, OXA, and oxytocin levels in CSF were measured. RESULTS: In the NW group, peripheral ApoA-I levels were higher, while ApoB levels were lower than in the OW/OB group (all p < 0.05). CSF NPY exhibited a positive correlation with peripheral ApoA-I in the NW group (r = 0.39, p = 0.001). Notably, participants with higher CSF NPY levels had higher peripheral ApoA-I levels in the NW group and lower peripheral ApoA-I levels in the OW/OB group, showing the significant moderating effect of BMI on this association (R2 = 0.144, ß=-0.54, p < 0.001). The correlation between ghrelin, OXA and oxytocin in CSF and peripheral ApoB in both groups exhibited opposing trends (Ghrelin: r = -0.03 and r = 0.04; OXA: r = 0.23 and r=-0.01; Oxytocin: r=-0.09 and r = 0.04). CONCLUSION: This study provides hitherto undocumented evidence that BMI moderates the relationship between CSF NPY and peripheral ApoA-I levels. It also reveals the protective role of NPY in the NW population, contrasting with its risk factor role in the OW/OB population, which was associated with the at-risk for cardiovascular disease.

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Bone has traditionally been viewed in the context of its structural contribution to the human body. Foremost providing necessary support for mobility, its roles in supporting calcium homeostasis and blood cell production are often afterthoughts. Recent research has further shed light on the ever-multifaceted role of bone and its importance not only for structure, but also as a complex endocrine organ producing hormones responsible for the autoregulation of bone metabolism. Osteocalcin is one of the most important substances produced in bone tissue. Osteocalcin in circulation increases insulin secretion and sensitivity, lowers blood glucose, and decreases visceral adipose tissue. In males, it has also been shown to enhance testosterone production by the testes. Neuropeptide Y is produced by various cell types including osteocytes and osteoblasts, and there is evidence suggesting that peripheral NPY is important for regulation of bone formation. Hormonal disorders are often associated with abnormal levels of bone turnover markers. These include commonly used bone formation markers (bone alkaline phosphatase, osteocalcin, and procollagen I N-propeptide) and commonly used resorption markers (serum C-telopeptides of type I collagen, urinary N-telopeptides of type I collagen, and tartrate-resistant acid phosphatase type 5b). Bone, however, is not exclusively comprised of osseous tissue. Bone marrow adipose tissue, an endocrine organ often compared to visceral adipose tissue, is found between trabecula in the bone cortex. It secretes a diverse range of hormones, lipid species, cytokines, and other factors to exert diverse local and systemic effects.

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Neuropeptide Y (NPY) and related peptides have been proposed as promising biomarkers for the diagnosis of prostate cancer by previous immunoassays and immunohistochemical studies. In this study, we evaluated the additional value of NPY and related peptides compared with prostate-specific antigen (PSA). We performed a comprehensive analysis of NPY, its precursors, and metabolite concentrations in both plasma and tissue samples from 181 patients using a highly specific liquid chromatography tandem mass spectrometry method. Compared with PSA, NPY and related peptides (NPYs) were less accurate at diagnosing significant prostate cancer. Combinations of NPYs in a stepwise approach did not improve a model that would be beneficial for patients. NPY may be beneficial for patients presenting with a PSA concentration in the gray area between 4 and 9 ng/ml, but the strength of this conclusion is limited. Thus, the use of NPYs as standalone or in combination with other variables, such as PSA, prostate volume, or age, to improve the diagnosis is not supported by our study. Patient summary: This study evaluated neuropeptide Y (NPY) of the family of endogenous peptides as a new biomarker to diagnose prostate cancer. We found that NPY in a patient's blood was not more helpful at diagnosing prostate cancer than the standard prostate-specific antigen blood test. Further research is needed to explore the potential of NPY and related peptides in specific subgroups of patients.

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Neuropeptide Y (NPY) plays a crucial role in controlling energy homeostasis and feeding behaviour. The role of NPY neurons located in the arcuate nucleus of the hypothalamus (Arc) in responding to homeostatic signals has been the focus of much investigation, but most studies have used AgRP promoter-driven models, which do not fully encompass Arc NPY neurons. To directly investigate NPY-expressing versus AgRP-expressing Arc neurons function, we utilised chemogenetic techniques in NPY-Cre and AgRP-Cre animals to activate Arc NPY or AgRP neurons in the presence of food and food-related stimuli. Our findings suggest that chemogenetic activation of the broader population of Arc NPY neurons, including AgRP-positive and AgRP-negative NPY neurons, has equivalent effects on feeding behaviour as activation of Arc AgRP neurons. Our results demonstrate that these Arc NPY neurons respond specifically to caloric signals and do not respond to non-caloric signals, in line with what has been observed in AgRP neurons. Activating Arc NPY neurons significantly increases food consumption and influences macronutrient selection to prefer fat intake.

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The hormone Neuropeptide Y (NPY) plays critical roles in feeding, satiety, obesity, and weight control. However, its complex peptide structure has hindered the development of fast and biocompatible detection methods. Previous studies utilizing electrochemical techniques with carbon fiber microelectrodes (CFMEs) have targeted the oxidation of amino acid residues like tyrosine to measure peptides. Here, we employ the modified sawhorse waveform (MSW) to enable voltammetric identification of NPY through tyrosine oxidation. Use of MSW improves NPY detection sensitivity and selectivity by reducing interference from catecholamines like dopamine, serotonin, and others compared to the traditional triangle waveform. The technique utilizes a holding potential of -0.2 V and a switching potential of 1.2 V that effectively etches and renews the CFME surface to simultaneously detect NPY and other monoamines with a sensitivity of 5.8 ± 0.94 nA/µM (n = 5). Furthermore, we observed adsorption-controlled, subsecond NPY measurements with CFMEs and MSW. The effective identification of exogenously applied NPY in biological fluids demonstrates the feasibility of this methodology for in vivo and ex vivo studies. These results highlight the potential of MSW voltammetry to enable fast, biocompatible NPY quantification to further elucidate its physiological roles.

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