Regulation Of Feeding Research Articles

Chronic olanzapine treatment leads to increased opioid receptor expression and changes in feeding regulating neurons in the female rat hypothalamus

Opioid receptor antagonists have shown increasing promise as an adjunct therapy to psychotropic medication. The goal is to reduce the weight gain and metabolic adverse effects that are associated with certain second-generation antipsychotics, such as olanzapine and clozapine. In this study, female rats were treated for 4 weeks with a long-acting injectable formulation of olanzapine to assess effects on hypothalamic feeding regulation. Using quantitative spatial in situ hybridization and receptor autoradiography, expression levels of the mu, kappa and delta opioid receptors were defined in the five hypothalamic areas: paraventricular nucleus (PVN), arcuate nucleus (ARC), ventromedial nucleus (VMN), dorsomedial nucleus (DMN) and lateral hypothalamus (LH). In addition, hypothalamic neuron number and size were estimated using the unbiased optical fractionator and spatial rotator methods. Hyperphagia was observed after only 24hours of olanzapine treatment, with continued weight gain throughout the duration of the study. In contrast, the observed food intake reversed to control levels after 2 weeks of olanzapine treatment. Chronic olanzapine treatment increased expression of kappa opioid receptor mRNA and receptor availability in the PVN, as well as increased mu opioid receptor availability in the PVN, ARC and VMN. These changes were accompanied by fewer anorexigenic proopiomelanocortin-expressing neurons of the ARC and corticotropin-releasing hormone expressing neurons of the PVN. This study links olanzapine-driven metabolic effects to increased opioid receptor expression in the hypothalamus, thus providing a rationale for the positive effects of using opioid receptor antagonists to relieve olanzapine adverse effects.

Holistic inside and outside: The impact of food taste on ARCAGRP neuron activity in feeding regulation

The activities of appetite-regulated neurons-ARCAGRP neurons-are modulated by multi-level feedback signals during feeding. In this issue of Neuron, Aitken etal.1 expand our understanding of the feedback control within feeding circuits, revealing that food taste signals can causally and precisely regulate meal patterns through ARCAGRP neurons.

Extrinsic and intrinsic regulation of blood feeding in mosquitoes.

Mosquitoes obtain large amounts of blood from hosts in a short period of time. To efficiently obtain high-quality blood without being noticed by the host, mosquitoes sense external factors such as the taste of the host blood and the surrounding environment, and integrate these signals with their own internal information to determine whether to initiate blood feeding and how long to continue feeding. With the development of gene editing and behavior monitoring techniques, the factors that control blood feeding are being identified. Elucidating the factors that contribute to blood feeding is expected to provide new ideas for artificially controlling blood feeding, which has often been overlooked behind host attraction mechanisms. Furthermore, understanding salivary components, mechanisms controlling satiety in feeding, and differences between sugar feeding and blood feeding would help us understand how some mosquitoes have adopted and developed blood feeding over the course of evolution.

Pharyngeal Pumping Assay for Quantifying Feeding Behavior in Caenorhabditis elegans.

C. elegans is a well-established nematode model organism, with 83% of its genes conserved in humans with translation potential. C. elegans is translucent, with clearly defined cellular organization, and robustly identifiable under a microscope, being an excellent model for studying feeding behavior. Its neuromuscular pharyngeal pump undergoes a pumping motion that can be quantified to study feeding behavior at specific treatment conditions and in genetically modified worms. Understanding the evolutionarily conserved feeding behaviors and regulatory signals is vital, as unhealthy eating habits increase the risk of associated diseases. The current protocol was developed to identify and study evolutionary conserved signals regulating feeding behavior. The protocol described here is very robust in calculating the pumping rate (pumping per minute) as it directly counts the pharyngeal pumping for 30 s. This protocol uses basic laboratory instrumentation, such as a stereomicroscope with an attached camera and a computer with a video program that can be used to count manually. The advantages of studying C. elegans feeding include understanding the genetic basis of feeding regulation, dysregulation of feeding behavior in a disease model, the influence of toxic or environmental substances in feeding behavior, and modulation of feeding behavior by pharmacological agents. Key features • Quantifies pharyngeal pumping, which can be used to study up/downstream signaling in feeding regulation. • Uses a phenotype (pharyngeal pumping) that is easy to score. • Requires only a stereomicroscope with a camera to record the pharyngeal pumping, which can be counted manually.

Globular adiponectin, acting via AdipoR1, regulates food intake of Siberian sturgeon (Acipenser baerii) in a mTOR dependent manner

Adiponectin (AdipoQ) is a hormone that regulates food intake and energy homeostasis in mammals. The globular adiponectin (gAd) has been reported involved in the regulation of appetite, but the regulatory role and mechanism in fish remains unelucidated. Using Siberian sturgeon as a model of Chondrostei, the recombinant gAd protein of Siberian sturgeon (SsgAd) was produced by Escherichia coli expression system and verified using western blotting. Intraperitoneal injection of recombinant SsgAd protein at 100 ng/g BW suppressed food intake 1 h after administration. Peripheral injection of SsgAd protein caused the upregulation of anorexigenic pyy expression in the valvula intestine, but did not affect cck expression in the valvula intestine and orexigenic ghrelin expression in the stomach. The SsgAd administration significantly increased the hypothalamic expressions of pomc and decreased npy, agrp, and cart expression. In addition, SsgAd recombinant protein promoted adipor1, ampkα2, akt, and mtor mRNA expressions within the hypothalamus, whereas inhibited ampkβ1, ampkβ2 and ampkγ2 mRNA expression, suggesting AMPK and mTOR signaling pathways might be related to SsgAd protein-mediated anorexia activity. Furthermore, the injection of an mTOR antagonist (rapamycin) reversed the reduced food intake and npy, agrp, and cart expression due to the peripheral injection of SsgAd, as well as the increased pomc expression induced by SsgAd, which were not observed after AMPK antagonist (dorsomorphin) treatment. In summary, the current study, for the first time, suggest that the anorexigenic function of SsgAd might bind with AdipoR1 and activate the mTOR signal pathway to affect the expression of hypothalamic appetite factors in Siberian sturgeon. This study provides new insight into the molecular mechanism of AdipoQ in feeding regulation in fish, and a basis for further exploration on physiological function of AdipoQ.

Cloning and expression profiling of peptide YY in the brain of common carp, Cyprinus carpio

Peptide YY (PYY) is an anorectic brain-gut pancreatic peptide that helps in feeding regulation by reducing appetite and is well characterized in mammals. The role of PYY in relation to brain is least studied in mammals as well as in lower vertebrates including fish, however high expression was evident in male reproductive tissue. In this regard, this study attempts to evaluate the significance of PYY in the brain of common carp, Cyprinus carpio. As a first step, the cDNA of PYY from brain of adult male carp was cloned. Following which expression analysis was performed using juvenile and adult fish. The differential distribution pattern in various regions of brain and ontogeny expression analysis indicated that PYY may involve in physiological processes related to brain-pituitary axis. In addition, a significant decrease in neuropeptide Y expression was observed upon PYY- endoribonuclease-prepared small interfering RNA transfection in brain cells, in vitro indicating plausible PYY-NPY interaction in brain-pituitary axis of common carp.

Role of Cholecystokinin (cck) in Feeding Regulation of Largemouth Bass (Micropterus salmoides): Peptide Activation and Antagonist Inhibition.

This study investigated the role of cholecystokinin (cck) in the feeding regulation of largemouth bass (Micropterus salmoides) via peptide activation and antagonist inhibition. The results show that the cck gene was expressed in various tissues, with the highest expression level occurring in the brain. Feeding, continuous feeding, and refeeding after fasting could significantly improve the mRNA levels of cck in the brain. Moreover, the activation of cck via injecting an exogenous CCK peptide could inhibit feed intake by regulating the mRNA levels of anorexigenic and feed-promoting factors in the brain and intestine. Furthermore, the CCK peptide reduced feed intake; however, the presence of an antagonist (Ly225910-CCK1R and devazepide-CCK2R) could reverse this effect through regulating the mRNA levels of anorexigenic and feed-promoting factors in the brain and intestine. Treatment with devazepide + CCK (CCK2R) reversed feed intake more effectively than Ly225910 + CCK (CCK1R) treatment. In summary, cck could regulate the feed intake of largemouth bass through regulating feeding-related genes in the brain and intestine. In addition, cck required binding with the receptor to inhibit feed intake more effectively in largemouth bass, and the binding effect of CCK1R was better than that of CCK2R.

LEAP2 is associated with impulsivity and reward sensitivity depending on the nutritional status and decreases with protein intake in humans.

Liver-expressed antimicrobial peptide 2 (LEAP2) dynamics in human plasma and its association with feeding behaviour remain poorly understood. Therefore, this study aims: (a) to investigate fasting LEAP2 in participants with normal weight or with overweight or mild obesity (OW/OB); (b) to study the association between fasting LEAP2 and anthropometric and metabolic traits, feeding behaviour, LEAP2 genetic variants and blood cell DNA methylation status; and (c) to ascertain postprandial changes in LEAP2 after high protein intake and the association with feeding behaviour and food intake. Anthropometric and behavioural measures, genotyping, methylation profiling, plasma glucose and LEAP2 concentrations were assessed in 327 females and males. A subgroup of 123 participants received an ad libitum high-protein meal, and postprandial LEAP2 concentration and behavioural measures were assessed. LEAP2 concentration was higher in participants with OW/OB (p < 0.001) and in females (p < 0.001), and was associated with LEAP2 single nucleotide polymorphisms rs765760 (p = 0.012) and rs803223 (p = 0.019), but not with LEAP2 methylation status. LEAP2 concentration was directly related to glycaemia (p = 0.001) and fullness (p = 0.003) in participants with normal weight, whereas it was associated with body mass index (p = 0.018), waist circumference (p = 0.014) and motor impulsivity in participants with OW/OB (p = 0.005). A negative association with reward responsiveness was observed in participants with OW/OB (p = 0.023). LEAP2 concentration was inversely associated with food intake (p = 0.034) and decreased after a high-protein meal (p < 0.001), particularly in women (p = 0.002). Increased LEAP2 in participants with OW/OB is associated with behavioural characteristics of obesity. Our results show sexual dimorphism in LEAP2 concentration before and after food intake and highlight the role of LEAP2 in feeding regulation.

Central regulation of feeding and body weight by ciliary GPR75.

Variants of the G protein-coupled receptor 75 (GPR75) are associated with a lower BMI in large-scale human exome-sequencing studies. However, how GPR75 regulates body weight remains poorly understood. Using random germline mutagenesis in mice, we identified a missense allele (Thinner) of Gpr75 that resulted in a lean phenotype and verified the decreased body weight and fat weight in Gpr75-knockout (Gpr75-/-) mice. Gpr75-/- mice displayed reduced food intake under high-fat diet (HFD) feeding, and pair-feeding normalized their body weight. The endogenous GPR75 protein was exclusively expressed in the brains of 3xFlag-tagged Gpr75-knockin (3xFlag-Gpr75) mice, with consistent expression across different brain regions. GPR75 interacted with Gαq to activate various signaling pathways after HFD feeding. Additionally, GPR75 was localized in the primary cilia of hypothalamic cells, whereas the Thinner mutation (L144P) and human GPR75 variants in individuals with a lower BMI failed to localize in the cilia. Loss of GPR75 selectively inhibited weight gain in HFD-fed mice but failed to suppress the development of obesity in leptin ob-mutant (Lepob-mutant) mice and adenylate cyclase 3-mutant (Adcy3-mutant) mice on a chow diet. Our data reveal that GPR75 is a ciliary protein expressed in the brain and plays an important role in regulating food intake.

The dual action of basal forebrain in feeding regulation.

The dual action of basal forebrain in feeding regulation.

A dorsal hippocampus-prodynorphinergic dorsolateral septum-to-lateral hypothalamus circuit mediates contextual gating of feeding.

Adaptive regulation of feeding depends on linkage of internal states and food outcomes with contextual cues. Human brain imaging has identified dysregulation of a hippocampal-lateral hypothalamic area (LHA) network in binge eating, but mechanistic instantiation of underlying cell-types and circuitry is lacking. Here, we identify an evolutionary conserved and discrete Prodynorphin (Pdyn)-expressing subpopulation of Somatostatin (Sst)-expressing inhibitory neurons in the dorsolateral septum (DLS) that receives primarily dorsal, but not ventral, hippocampal inputs. DLS(Pdyn) neurons inhibit LHA GABAergic neurons and confer context- and internal state-dependent calibration of feeding. Viral deletion of Pdyn in the DLS mimicked effects seen with optogenetic silencing of DLS Pdyn INs, suggesting a potential role for DYNORPHIN-KAPPA OPIOID RECEPTOR signaling in contextual regulation of food-seeking. Together, our findings illustrate how the dorsal hippocampus has evolved to recruit an ancient LHA feeding circuit module through Pdyn DLS inhibitory neurons to link contextual information with regulation of food consumption.

The Self-Control of Eating.

Many individuals struggle to regulate their own consumption of food. Beginning with general theories of self-control, we review psychological factors that have been shown to influence the regulation of eating, including those related to particular personality variables, such as external eating, restrained eating, and reward sensitivity, as well as situational constraints, including normative influences, emotions, and calorie deprivation. Strategies for the self-control of eating, including reappraisal, effortful inhibition, and various automatic strategies are also reviewed, along with a discussion of the strengths and limitations of historical and contemporary psychological studies investigating food consumption. Whereas extensive examinations of food preferences and body weight have appeared in the psychological literature, we call for more robust research that prioritizes actual eating as the primary dependent measure.

Profiling and health risk assessment of trace metal contents in bovine tissues: A case study in Gondar City, Ethiopia

This study aimed to determine six trace metal (Cu, Mn, Zn, Cd, Cr, and Pb) concentrations in three bovine tissues (kidney, liver and muscle) from Gondar City abattoir, Ethiopia, and assess associated health risks. Samples were digested with HNO3/HClO4, and metal concentrations were analyzed by Inductively Coupled Plasma Optical Emission Spectroscopy. Zn exhibited the highest concentration in muscle (52.1 mg/kg), whereas Cd was below the LOD (0.6 µg/kg) in all muscle samples. The levels of Cd, Cr, and Mn in liver and kidney tissues, as well as Zn in muscle, exceeded FAO/WHO safety thresholds. Principal component analysis revealed distinct metal accumulation patterns among the tissues where liver is the target organ for accumulation of Pb, Mn and Cu, while kidney appears to be the organ of preference for Cd and Cr accumulation. Zn had the highest chronic daily intake for both children and adults, followed by Cu. Hazard index values for both age groups were below one, indicating no non-carcinogenic risks. However, the incremental lifetime cancer risks and cumulative carcinogenic risks of Cr exceeded the tolerable limit for adults and children, indicating a high cancer likelihood from this trace metal. In contrast, the incremental lifetime cancer risks of Pb for both adults and children were within acceptable limits. In conclusion, cumulative carcinogenic risk values indicate that consuming muscle tissue poses health risks for both adults and children, highlighting the need for stricter cattle feed regulations in the study area to safeguard public health.

The Hypothesis and Research on the Regulation of Mouse Feeding Behavior by Astrocytes in the Lateral Hypothalamic Area

Numerous studies have shown that the central nervous system plays a crucial role in regulating feeding behavior [1]. Within the central nervous system, many nuclei and neural circuitry are involved in regulating feeding behavior, such as the ventral tegmental area (VTA), lateral hypothalamus (LH), tuberomammillary nucleus (TN), and amygdala (CeA). Among these, the lateral hypothalamus is a critical target for the regulation of homeostatic feeding. Previous studies on LH regulation of feeding behavior have mostly focused on neurons and neural circuits, with relatively fewer studies on astrocytes.

Fibrinopeptide A-induced blood-feeding arrest in the yellow fever mosquito Aedes aegypti

Female mosquitoes engage in blood feeding from their hosts to facilitate egg maturation but cease feeding once a sufficient blood meal has been acquired. Abdominal distention has been proposed as a contributing factor; however, it has also been suggested that there are chemical controls. In this study, we focus on negative chemical regulators of blood feeding, particularly those present in the host blood. Serum derived from animal blood inhibits the feeding of ATP, a phagostimulant of blood feeding in Aedes aegypti. Fibrinopeptide A (FPA), a 16-amino acid peptide cleaved from fibrinogen during blood coagulation, serves as an inhibitory factor in the serum. Our findings suggest that blood-feeding arrest in female mosquitoes is triggered by the detection of FPA in the host blood, which increases as blood coagulation proceeds in the mosquito's midgut, highlighting the role of host-derived substances as negative regulators of mosquito behavior.

The short-chain fatty acid acetate modulates orexin/hypocretin neurons: A novel mechanism in gut-brain axis regulation of energy homeostasis and feeding

The short-chain fatty acids (SCFAs) acetate, propionate and butyrate, the major products of intestinal microbial fermentation of dietary fibres, are involved in fine-tuning brain functions via the gut-brain axis. However, the effects of SCFAs in the hypothalamic neuronal network regulating several autonomic-brain functions are still unknown. Using NMR spectroscopy, we detected a reduction in brain acetate concentrations in the hypothalamus of obese leptin knockout ob/ob mice compared to lean wild-type littermates. Therefore, we investigated the effect of acetate on orexin/hypocretin neurons (hereafter referred as OX or OX-A neurons), a subset of hypothalamic neurons regulating energy homeostasis, which we have characterized in previous studies to be over-activated by the lack of leptin and enhancement of endocannabinoid tone in the hypothalamus of ob/ob mice.We found that acetate reduces food-intake in concomitance with a reduction of orexin neuronal activity in ob/ob mice. This was demonstrated by evaluating food-intake behaviour and orexin-A/c-FOS immunoreactivity coupled with patch-clamp recordings in Hcrt-eGFP neurons, quantification of prepro-orexin mRNA, and immunolabeling of GPR-43, the main acetate receptor. Our data provide new insights into the mechanisms of the effects of chronic dietary supplementation with acetate, or complex carbohydrates, on energy intake and body weight, which may be partly mediated by inhibition of orexinergic neuron activity.

Tyramine-Mediated Hyperactivity Modulates the Dietary Habits in Helicoverpa armigera.

Helicoverpa armigera exhibits extensive variability in feeding habits and food selection. Neuronal regulation of H. armigera feeding behavior is primarily influenced by biogenic amines such as Tyramine (TA) and Octopamine (OA). The molecular responses of H. armigera to dietary challenges in the presence of TA or OA have yet to be studied. This investigation dissects the impact of OA and TA on H. armigera feeding choices and behaviors under non-host nutritional stress. It has been observed that feeding behavior remains unaltered during the exogenous administration of OA and TA through an artificial diet (AD). Ingestion of higher OA or TA concentrations leads to increased mortality. OA and TA treatment in combination with host and non-host diets results in the induction of feeding and higher locomotion toward food, particularly in the case of TA treatment. Increased expression of markers, prominin-like, and tachykinin-related peptide receptor-like transcripts further assessed increased locomotion activity. Insects subjected to a non-host diet with TA treatment exhibited increased feeding and overexpression of the feeding indicator, the Neuropeptide F receptor, and the feeding regulator, Sulfakinin, compared with other conditions. Expression of sensation and biogenic amine synthesis genesis elevated in insects fed a non-host diet in combination with OA or TA. Metabolomics analysis revealed a decreased concentration of the feeding behavior elicitor, dopamine, in insects fed a non-host diet containing TA. This work highlights the complex interplay between biogenic amine functions during dietary stress and suggests the role of tyramine in feeding promotion under stressed conditions.

Distinct patterns of feed intake and their association with growth performance in broilers

Improving feed utilization is a vital strategy to meet the growing global demand for meat and promote sustainable food production. Over the past few decades, significant improvements in the feed intake (FI) and feed utilization efficiency of broilers have been achieved through advanced breeding procedures, although dynamic changes in FI and their effects on the feed conversion ratio (FCR) have remained unclear. In this study, we measured individual weekly FI and body weight of 274 male broilers to characterize the dynamic FI patterns and investigate their relationship with growth performance. The broilers were from 2 purebred lines and their crossbreed and measurements were collected from 4 to 6 wk of age. Overall, a continuous increase in the weekly FI occurred from 4 to 6 wk of age, whereas the body weight gain (BWG) reached an inflection point in wk 5. The dynamic change in weekly FI was observed to follow 3 distinct FI patterns: pattern 1, a continuous weekly increase in FI; pattern 2, an increase followed by a plateau; pattern 3, an increase followed by a decrease. The prevalence of these patterns was similar in the purebred and crossbred populations: pattern 2 was most frequent, followed by a moderate proportion of pattern 1, and the lowest proportion of pattern 3. Broilers following pattern 1 displayed significantly better growth performance and feed utilization efficiency than those following pattern 3, emphasizing the importance of maintaining good appetite in the last stage of broiler production. In summary, this study has characterized the dynamic patterns of FI and their association with growth performance. Our results offer a new foundation for improving feed utilization efficiency and investigating feeding regulation in broilers.

Molecular and functional mapping of the neuroendocrine hypothalamus: a new era begins.

Recent advances in neuroscience tools for single-cell molecular profiling of brain neurons have revealed an enormous spectrum of neuronal subpopulations within the neuroendocrine hypothalamus, highlighting the remarkable molecular and cellular heterogeneity of this brain area. Neuronal diversity in the hypothalamus reflects the high functional plasticity of this brain area, where multiple neuronal populations flexibly integrate a variety of physiological outputs, including energy balance, stress and fertility, through crosstalk mechanisms with peripheral hormones. Intrinsic functional heterogeneity is also observed within classically 'defined' subpopulations of neuroendocrine neurons, including subtypes with distinct neurochemical signatures, spatial organisation and responsiveness to hormonal cues. The aim of this review is to critically evaluate past and current research on the functional diversity of hypothalamic neuroendocrine neurons and their plasticity. It focuses on how this neuronal plasticity in this brain area relates to metabolic control, feeding regulation and interactions with stress and fertility-related neural circuits. Our analysis provides an original framework for improving our understanding of the hypothalamic regulation of hormone function and the development of neuroendocrine diseases.

Neuropeptide Y receptor Y8b (npy8br) regulates feeding and digestion in Japanese medaka (Oryzias latipes) larvae: evidence from gene knockout.

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.