Regulation Of Feeding Research Articles

GABAB receptor signaling in the caudate putamen is involved in binge-like consumption during a high fat diet in mice

Previous studies suggest that signaling by the gamma-aminobutyric acid (GABA) type B receptor (GABABR) is involved in the regulation of binge eating, a disorder which might contribute to the development of obesity. Here, we show that intermittent access to a high fat diet (HFD) induced binge-like eating behavior with activation of dopamine receptor d1 (drd1)-expressing neurons in the caudate putamen (CPu) and nucleus accumbens (NAc) in wild-type (WT) mice. The activation of drd1-expressing neurons during binge-like eating was substantially increased in the CPu, but not in the NAc, in corticostriatal neuron-specific GABABR-deficient knockout (KO) mice compared to WT mice. Treatment with the GABABR agonist, baclofen, suppressed binge-like eating behavior in WT mice, but not in KO mice, as reported previously. Baclofen also suppressed the activation of drd1-expressing neurons in the CPu, but not in the NAc, during binge-like eating in WT mice. Thus, our data suggest that GABABR signaling in CPu neurons expressing drd1 suppresses binge-like consumption during a HFD in mice.

Identification, tissue distribution, and anorexigenic effect of amylin in Siberian sturgeon (Acipenser baeri)

Amylin is a 37-amino acid polypeptide that has been found to be involved in feeding regulation in some mammals, birds, and goldfish. We cloned amylin of Siberian sturgeon and detected its distribution pattern in 15 tissues. The expression levels in the periprandial period (pre-and post-feeding), the changes in the food intake, and the expression levels of related appetite factors after the intraperitoneal injection of amylin were detected. The expression of amylin was found to be the highest in the hypothalamus. Compared with 1 h pre-feeding, the expression levels of amylin in the hypothalamus and duodenum were increased significantly 1 h post-feeding. Compared with the control group (saline), intraperitoneal injection of 50 ng/g, 100 ng/g, and 200 ng/g of amylin significantly inhibited food intake at 1 h post injection, but not at 3 h and 6 h. The injection of 50 ng/g, 100 ng/g, and 200 ng/g amylin significantly inhibited the cumulative feed. After 1 h of 50 ng/g amylin injection, the levels of MC4R and somatostatin in the hypothalamus increased significantly, while the levels of amylin and NPY decreased significantly. The levels of CCK in the valvular intestine were increased significantly. Insulin in the duodenum was also increased significantly, but there was no significant change in ghrelin in the duodenum. These results show that amylin inhibits feeding in Siberian sturgeon by down-regulating the appetite-stimulating factor NPY and up-regulating the appetite-suppressing factors somatostatin, MC4R, CCK, and insulin. This study provides a theoretical basis for studying the feeding function and action mechanisms of amylin in Siberian sturgeon.

AgRP neurons: Regulators of feeding, energy expenditure, and behavior.

Neurons in the hypothalamic arcuate nucleus (ARC) that express agouti-related peptide (AgRP) govern a critical aspect of survival: the drive to eat. Equally important to survival is the timing at which food is consumed-seeking or eating food to alleviate hunger in the face of a more pressing threat, like the risk of predation, is clearly maladaptive. To ensure optimal prioritization of behaviors within a given environment, therefore, AgRP neurons must integrate signals of internal need states with contextual environmental cues. In this state-of-the-art review, we highlight recent advances that extend our understanding of AgRP neurons, including the neural circuits they engage to regulate feeding, energy expenditure, and behavior. We also discuss key findings that illustrate how both classical feedback and anticipatory feedforward signals regulate this neuronal population and how the integration of these signals may be disrupted in states of energy excess. Finally, we examine both technical and conceptual challenges facing the field moving forward.

Do oxytocin neurones affect feeding?

There has been a long history of research on the effects of oxytocin on feeding behaviour. The classic-held view is that the neurohormone is anorexigenic at least in rodents, although the data for humans are not so clear cut. Likewise, a physiological role for oxytocin is disputed. Thus, although pharmacological, anatomical and physiological data suggest oxytocin may have a function in satiety signalling, this view is not supported by the latest research using the genetic recording and manipulation of oxytocin neurones. Here, we avoid a discussion of the pharmacological effects of oxytocin and examine evidence, from both sides of the argument, concerning whether the endogenous oxytocin system has a role in the regulation of normal feeding.

Seasonal expression and distribution of kisspeptin1 (kiss1) in the ovary and testis of freshwater catfish, Clarias batrachus: A putative role in steroidogenesis

The central role of kisspeptin (kiss) in mammalian reproduction is well established; however, its intra-gonadal role is poorly addressed. Moreover, studies investigating intra-gonadal role of kiss in fish reproduction are scanty, contradictory and inconclusive. The expression of kiss1 mRNA has been detected in the fish brain, and functionally attributed to the regulation of reproduction, feeding and behavior. The kiss1 mRNA has also been demonstrated in tissues other than the brain in some studies, but its cellular distribution and role at the tissue level have not been adequately addressed in fish. Therefore, an attempt was made in the present study to localize kiss1 in gonadal cells of the freshwater catfish, Clarias batrachus. This study reports the presence of kiss1 in the theca cells and granulosa cells of the ovarian oocytes and interstitial cells in the testis of the catfish. The role of kiss1 in the ovary and testis of the catfish was also investigated using kiss1 receptor (kiss1r) antagonist (p234). The p234 treatment decreased the production of 17β-estradiol in ovary and testosterone in the testis by lowering the activities of 3β-hydroxysteroid dehydrogenase and 17β-hydroxysteroid dehydrogenase under both, in vivo as well as in vitro conditions. The p234 treatment also arrested the progression of oogenesis, as evident from the low number of advancing/advanced oocytes in the treated ovary in comparison to the control ovary. It also reduced the area and perimeter of the seminiferous tubules in the treated catfish testis. Thus, our findings suggest that kiss is involved in the regulation of gonadal steroidogenesis, independent of known endocrine/ autocrine/ paracine regulators, and thereby it accelerates gametogenic processes in the freshwater catfish.

Intracerebroventricular administration of α-melanocyte-stimulating hormone (α-MSH) enhances thigmotaxis and induces anxiety-like behavior in the goldfish Carassius auratus

α-Melanocyte-stimulating hormone (α-MSH) is a body pigmentation-regulating hormone secreted from the intermediate lobe of the pituitary in vertebrates. It is also produced in the brain, and acts as an anorexigenic neuropeptide involved in feeding regulation. In rodents, intracerebroventricular (ICV) administration of α-MSH has been shown to affect not only feeding behavior, but also psychomotor activity. However, there is still no information regarding the psychophysiological effects of α-MSH on behavior in fish. Therefore, we examined the effect of synthetic α-MSH on psychomotor activity in goldfish. Since this species prefers the edge to the central area of a tank, we used this as a preference test for assessing psychomotor activity. When α-MSH was administered ICV at 1 and 10 pmol g−1 body weight (BW), the time spent in the edge area of a tank was prolonged at 10 pmol g−1 BW. However, α-MSH at these doses did not affect locomotor activity. The action of α-MSH mimicked those of FG-7142 (a central-type benzodiazepine receptor (CBR) inverse agonist with an anxiogenic effect) at 10 pmol g−1 BW and melanotan II (a melanocortin 4 receptor (MC4R) agonist) at 50 pmol g−1 BW, whereas ICV administration of tofisopam (a CBR agonist with an anxiolytic effect) at 10 pmol g−1 BW prolonged the time spent in the central area. The anxiogenic-like effect of α-MSH was abolished by treatment with the MC4R antagonist HS024 at 50 pmol g−1 BW. These data indicate that α-MSH affects psychomotor activity in goldfish, and exerts an anxiogenic-like effect via the MC4R-signaling pathway.

Hypothalamic control of interoceptive hunger

While energy balance is critical to survival, many factors influence food intake beyond caloric need or "hunger." Despite this, some neurons that drive feeding in mice are routinely referred to as "hunger neurons," whereas others are not. To understand how specific hypothalamic circuits control interoceptive hunger, we trained mice to discriminate fasted from sated periods. We then manipulated three hypothalamic neuronal populations with well-known effects on feeding while mice performed this task. While activation of ARCAGRP neurons in sated mice caused mice to report being food-restricted, LHVGAT neuron activation or LHVGLUT2 neuron inhibition did not. In contrast, LHVGAT neuron inhibition or LHVGLUT2 neuron activation in fasted mice attenuated natural hunger, whereas ARCAGRP neuron inhibition did not. Each neuronal population evoked distinct effects on food consumption and reward. After satiety- or sickness-induced devaluation, ARCAGRP neurons drove calorie-specific feeding, while LHVGAT neurons drove calorie-indiscriminate food intake. Our data support a role for ARCAGRP neurons in homeostatic feeding and implicate them in driving a hunger-like internal state that directs behavior toward caloric food sources. Moreover, manipulations of LH circuits did not evoke hunger-like effects in sated mice, suggesting that they may govern feeding more related to reward, compulsion, or generalized consumption than to energy balance, but also that these LH circuits can be powerful negative appetite modulators in fasted mice. This study highlights the complexity of hypothalamic feeding regulation and can be used as a framework to characterize how other neuronal circuits affect hunger and identify potential therapeutic targets for eating disorders.

Mouse Spexin: (II) Functional Role as a Satiety Factor inhibiting Food Intake by Regulatory Actions Within the Hypothalamus.

Spexin (SPX) is a pleiotropic peptide with highly conserved protein sequence from fish to mammals and its biological actions are mediated by GalR2/GalR3 receptors expressed in target tissues. Recently, SPX has been confirmed to be a novel satiety factor in fish species but whether the peptide has a similar function in mammals is still unclear. Using the mouse as a model, the functional role of SPX in feeding control and the mechanisms involved were investigated. After food intake, serum SPX in mice could be up-regulated with elevations of transcript expression and tissue content of SPX in the glandular stomach but not in other tissues examined. As revealed by immunohistochemical staining, food intake also intensified SPX signals in the major cell types forming the gastric glands (including the foveolar cells, parietal cells, and chief cells) within the gastric mucosa of glandular stomach. Furthermore, IP injection of SPX was effective in reducing food intake with parallel attenuation in transcript expression of NPY, AgRP, NPY type 5 receptor (NPY5R), and ghrelin receptor (GHSR) in the hypothalamus, and these inhibitory effects could be blocked by GalR3 but not GalR2 antagonism. In agreement with the central actions of SPX, similar inhibition on feeding and hypothalamic expression of NPY, AgRP, NPY5R, and GHSR could also be noted with ICV injection of SPX. In the same study, in contrast to the drop in NPY5R and GHSR, SPX treatment could induce parallel rises of transcript expression of leptin receptor (LepR) and melanocortin 4 receptor (MC4R) in the hypothalamus. These findings, as a whole, suggest that the role of SPX as a satiety factor is well conserved in the mouse. Apparently, food intake can induce SPX production in glandular stomach and contribute to the postprandial rise of SPX in circulation. Through GalR3 activation, this SPX signal can act within the hypothalamus to trigger feedback inhibition on feeding by differential modulation of feeding regulators (NPY and AgRP) and their receptors (NPY5R, GHSR, LepR, and MC4R) involved in the feeding circuitry within the CNS.

The endocannabinoid system is modulated in reward and homeostatic brain regions following diet-induced obesity in rats: a cluster analysis approach.

ObjectivesIncreased availability of high-calorie palatable food in most countries has resulted in overconsumption of these foods, suggesting that excessive eating is driven by pleasure, rather than metabolic need. The behavior contributes to the rise in eating disorders, obesity, and associated pathologies like diabetes, cardiac disease, and cancers. The mesocorticolimbic dopamine and homeostatic circuits are interconnected and play a central role in palatable food intake. The endocannabinoid system is expressed in these circuits and represents a potent regulator of feeding, but the impact of an obesogenic diet on its expression is not fully known.MethodsFood intake and body weight were recorded in male Wistar rats over a 6-week free-choice regimen of high fat and sugar; transcriptional regulations of the endocannabinoid system were examined post-mortem in brain reward regions (prefrontal cortex, nucleus accumbens, ventral tegmental area, and arcuate nucleus). K-means cluster analysis was used to classify animals based on individual sensitivity to obesity and palatable food intake. Endocannabinoid levels were quantified in the prefrontal cortex and nucleus accumbens. Gene expression in dopamine and homeostatic systems, including ghrelin and leptin receptors, and classical homeostatic peptides, were also investigated.ResultsThe free-choice high-fat -and sugar diet induced hyperphagia and obesity in rats. Cluster analysis revealed that the propensity to develop obesity and excessive palatable food intake was differently associated with dopamine and endocannabinoid system gene expression in reward and homeostatic brain regions. CB2 receptor mRNA was increased in the nucleus accumbens of high sugar consumers, whereas CB1 receptor mRNA was decreased in obesity prone rats.ConclusionsTranscriptional data are consistent with observations of altered dopamine function in rodents that have access to an obesogenic diet and point to cannabinoid receptors as GPCR targets involved in neuroplasticity mechanisms associated with maladaptive intake of palatable food.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00394-021-02613-0.

Innervating the gut

Metabolism Sensory neurons that detect signals in the gut and relay them to the brain are an important feature of regulating food intake and metabolic responses to food. When such gut-brain signaling is impaired, overeating, weight gain, and metabolic dysfunction can occur. Borgmann et al. investigated feeding and glucose regulation by different sensory neurons that innervate the gut of mice. Their findings enabled reconstruction of peripheral and central sensory neuron projections and revealed differential innervation of the mucosal and muscular layers of the intestine and different regions of the gastrointestinal tract, likely reflecting distinct responses to specific signals in the gut. These subsets of neurons may provide targets for controlling metabolic diseases in the future. Cell Metab. 10.1016/j.cmet.2021.05.002 (2021).

Deciphering an AgRP-serotoninergic neural circuit in distinct control of energy metabolism from feeding

Contrasting to the established role of the hypothalamic agouti-related protein (AgRP) neurons in feeding regulation, the neural circuit and signaling mechanisms by which they control energy expenditure remains unclear. Here, we report that energy expenditure is regulated by a subgroup of AgRP neurons that send non-collateral projections to neurons within the dorsal lateral part of dorsal raphe nucleus (dlDRN) expressing the melanocortin 4 receptor (MC4R), which in turn innervate nearby serotonergic (5-HT) neurons. Genetic manipulations reveal a bi-directional control of energy expenditure by this circuit without affecting food intake. Fiber photometry and electrophysiological results indicate that the thermo-sensing MC4RdlDRN neurons integrate pre-synaptic AgRP signaling, thereby modulating the post-synaptic serotonergic pathway. Specifically, the MC4RdlDRN signaling elicits profound, bi-directional, regulation of body weight mainly through sympathetic outflow that reprograms mitochondrial bioenergetics within brown and beige fat while feeding remains intact. Together, we suggest that this AgRP neural circuit plays a unique role in persistent control of energy expenditure and body weight, hinting next-generation therapeutic approaches for obesity and metabolic disorders.

The Roles of Neuropeptide Y (Npy) and Peptide YY (Pyy) in Teleost Food Intake: A Mini Review.

Neuropeptide Y family (NPY) is a potent orexigenic peptide and pancreatic polypeptide family comprising neuropeptide Y (Npy), peptide YYa (Pyya), and peptide YYb (Pyyb), which was previously known as peptide Y (PY), and tetrapod pancreatic polypeptide (PP), but has not been exhaustively documented in fish. Nonetheless, Npy and Pyy to date have been the key focus of countless research studies categorizing their copious characteristics in the body, which, among other things, include the mechanism of feeding behavior, cortical neural activity, heart activity, and the regulation of emotions in teleost. In this review, we focused on the role of neuropeptide Y gene (Npy) and peptide YY gene (Pyy) in teleost food intake. Feeding is essential in fish to ensure growth and perpetuation, being indispensable in the aquaculture settings where growth is prioritized. Therefore, a better understanding of the roles of these genes in food intake in teleost could help determine their feeding regime, regulation, growth, and development, which will possibly be fundamental in fish culture.

CCHamide2-receptor regulates feeding behavior in the pea aphid, Acyrthosiphon pisum

Neuropeptide CCHamide-2 is a recently discovered peptide presents in many arthropods and it is the ligand of the CCHamide-2 receptor (CCHa2-R), which is playing a regulatory role in diverse physiological processes, such as feeding, insulin production, lipid metabolism, growth and reproduction, however, the function of this gene in aphids is still unknown. Here, we characterized and determined the presumed role of CCHa2-R signaling in the wingless pea aphid, Acyrthosiphon pisum. Quantitative real-time reverse transcription-PCR (qRT-PCR) revealed the expression levels of CCHa2-R transcripts in different development stages and different tissues, which indicates that the CCHa2-R expression was high in the first instar as compared to the upcoming nymphal instars and adult and was predominantly high in the brain. The CCHa2-R transcript levels were significantly up-regulated in starved aphids as compared to fed aphids. Moreover, RNAi knockdown by the injection of dsRNA−CCHa2-R significantly reduced the expression and also reduced their food intake in adult aphids, as revealed by electrical penetration graphs (EPGs) results. CCHa2-R-silencing was also shown to reduce reproduction but not survival in A. pisum. These observations suggest a role for the CCHa2-R pathway in the response of wingless parthenogenetic aphids to their nutritional status, and this role involves the regulation of the expression of CCHa2-R. Overall, the results of these experiments indicate that CCHa2-R plays a dominant role in the regulation of feeding in A. pisum.

Central administration of insulin and refeeding lead to Akt and ERK phosphorylation in the chicken medulla

The purpose of this study was to investigate whether medullary cellular signaling pathways contribute to feeding regulation in chickens. Fasting inhibited the phosphorylated protein and its rates of ERK but not Akt in the chicken medulla, while refeeding promoted Akt and ERK. Intraperitoneal administration of sulfate cholecystokinin 8 did not affect medullary Akt and ERK phosphorylation in chickens. Intracerebroventricular administration of insulin significantly induced the phosphorylation of Akt and ERK in the chicken medulla. These findings suggest that the medullary Akt and ERK pathways are involved in the appetite-suppressive pathway of insulin in chickens.

Molecular cloning and characterization of the novel adropin from tilapia (Oreochromis niloticus): Involvement in the control of food intake

Adropin has been shown to be involved in the regulation of food intake in mice. However, the mechanism of adropin in feeding regulation is still largely unknown. Using the tilapia, Oreochromis niloticus, we identified and characterized a novel form of adropin (designated adropin-b) encoding a 68-amino acid precursor. Although adropin-b shared low amino acid identities with its tilapia paralog (designated adropin-a), synteny analysis proved that tilapia adropin is orthologous to its human counterpart. The transcripts of adropin-b were ubiquitously expressed in various tissues with the highest levels in the olfactory bulb. A decrease in adropin-b mRNA levels was observed 1 h following a meal in the olfactory bulb, hypothalamus, and optic tectum, whereas fasting for 7 days induced an increase in adropin-b mRNA levels in the olfactory bulb, hypothalamus, and optic tectum of tilapia brain. However, no changes in adropin-a mRNA levels were observed in the postprandial and fasting state. Intraperitoneal injection of tilapia adropin-b was shown to increase food consumption, but adropin-a did not affect feeding. Co-treatment of the fish with adropin-b and neuropeptide Y (NPY) had no additive effects on appetite. The appetite stimulatory effects of adropin-b appeared to be mediated by upregulating the orexigenic Npy, Orexin, and Proapelin gene expression, paralleled by inhibition of the mRNA levels of anorexigenic proopiomelanocortin (Pomc) and cocaine-amphetamine-regulated transcript (Cart) in vivo and in vitro. These observations suggested that adropin-b participated in appetite control and gene regulation of central orexigenic and anorexigenic factors in a fish model.

Time-restricted feeding is associated with mental health in elderly Italian adults

ABSTRACT In recent years, mental disorders have represented a relevant public health problem due to their deleterious effect on quality of life and the difficulty of timely diagnosis. The growing trends have been shown to be highly influenced by modern society, unhealthy lifestyle and harmful dietary habits. Not only the specific foods or dietary patterns have been hypothesized to play a role on mental health; also, temporal regulation of feeding and fasting has emerged as an innovative strategy to prevent and treat mental health disease. The aim of this cross-sectional study was to investigate the association between time-restricted feeding (TRF) and mental health outcomes including perceived stress, depressive symptoms, and sleep quality assessed in a cohort of southern Italian adults. Demographic and dietary characteristics of 1,572 adults living in southern Italy were analyzed. Food frequency questionnaires were used to calculate dietary intakes; participants were also asked what time, on average, they consumed their meals to calculate the eating window of time and identify those eating within 8 hours or less. Logistic regression analyses were performed to test the association between mental health outcomes. After adjusting for potential confounding factors, including adherence to the Mediterranean diet and having breakfast/dinner, no associations were found between TRF and mental health outcomes; however, when performing the analyses by age groups, individuals older than 70 years having a feeding time window of 8 hours were less likely to have signs of mental health distress [odds ratio (OR) = 0.14, 95% confidence interval (CI): 0.03–0.65] compared to those having no feeding time restriction independently of diet quality; notably, adjusting for having breakfast nullified the association (OR = 0.13, 95% CI: 0.02–1.18), while adjusting for having dinner did not change it (OR = 0.14, 95% CI: 0.03–0.67). No further associations were found for specific mental health outcomes explored separately. In conclusion, restricting the daily time feeding window is associated with lower signs of mental health distress in individuals older than 70 years. Albeit preliminary, these findings on elderly individuals require further investigation using prospective design and an amended approach to control for fasting.

Growth hormone-releasing hormone antagonistic analog MIA-690 stimulates food intake in mice

In addition to its metabolic and endocrine effects, growth hormone-releasing hormone (GHRH) was found to modulate feeding behavior in mammals. However, the role of recently synthetized GHRH antagonist MIA-690 and MR-409, a GHRH agonist, on feeding regulation remains to be evaluated. We investigated the effects of chronic subcutaneous administration of MIA-690 and MR-409 on feeding behavior and energy metabolism, in mice. Compared to vehicle, MIA-690 increased food intake and body weight, while MR-409 had no effect. Both analogs did not modify locomotor activity, as well as subcutaneous, visceral and brown adipose tissue (BAT) mass. A significant increase of hypothalamic agouti-related peptide (AgRP) gene expression and norepinephrine (NE) levels, along with a reduction of serotonin (5-HT) levels were found after MIA-690 treatment. MIA-690 was also found able to decrease gene expression of leptin in visceral adipose tissue. By contrast, MR-409 had no effect on the investigated markers. Concluding, chronic peripheral administration of MIA-690 could play an orexigenic role, paralleled by an increase in body weight. The stimulation of feeding could be mediated, albeit partially, by elevation of AgRP gene expression and NE levels and decreased 5-HT levels in the hypothalamus, along with reduced leptin gene expression, in the visceral adipose tissue.

Gut-brain communication by distinct sensory neurons differently controls feeding and glucose metabolism

SummarySensory neurons relay gut-derived signals to the brain, yet the molecular and functional organization of distinct populations remains unclear. Here, we employed intersectional genetic manipulations to probe the feeding and glucoregulatory function of distinct sensory neurons. We reconstruct the gut innervation patterns of numerous molecularly defined vagal and spinal afferents and identify their downstream brain targets. Bidirectional chemogenetic manipulations, coupled with behavioral and circuit mapping analysis, demonstrated that gut-innervating, glucagon-like peptide 1 receptor (GLP1R)-expressing vagal afferents relay anorexigenic signals to parabrachial nucleus neurons that control meal termination. Moreover, GLP1R vagal afferent activation improves glucose tolerance, and their inhibition elevates blood glucose levels independent of food intake. In contrast, gut-innervating, GPR65-expressing vagal afferent stimulation increases hepatic glucose production and activates parabrachial neurons that control normoglycemia, but they are dispensable for feeding regulation. Thus, distinct gut-innervating sensory neurons differentially control feeding and glucoregulatory neurocircuits and may provide specific targets for metabolic control.

Effects of thyroxine and propylthiouracil on feeding behavior and the expression of hypothalamic appetite-regulating peptides and thyroid function in goldfish (Carassius auratus)

There is poor evidence for an association between thyroidal state, feeding and appetite regulation in fish. We assessed how an altered thyroid state influences feeding behavior, food intake and expression of hypothalamic appetite-regulating peptides (Klotho-α and Klotho-β; orexin, OX; cholecystokinin, CCK; agouti-related peptide, AgRP; cannabinoid receptor 1, CB1) in goldfish. We also measured the expressions of hypothalamic, pituitary and liver transcripts that regulate the thyroid [thyrotropin-releasing hormone (TRH), thyrotropin-releasing hormone receptor (TRH-R) type 1, thyroid stimulating hormone beta (TSHβ), deiodinases (DIO2, DIO3), UDP-glucuronosyltransferase (UGT1A1), thyroid receptor alpha and beta (TRα, TRβ)], and circulating levels of total thyroxine (tT4) and total triiodothyronine (tT3). Goldfish were implanted with propylthiouracil (PTU) or T4 osmotic pumps for 12 days. T4- treatment increased feeding behavior but not food intake, increased central TSHβ and DIO2, and hepatic DIO2 transcript expression and increased central DIO3 mRNA. Under hyperthyroid conditions, hypothalamic Klotho and CCK expressions were downregulated, suggesting an increased metabolic state and a hypothalamic response to regulate energy balance. AgRP, OX and CB1 were not affected by T4 treatment. PTU had no effect on any of the parameters examined, suggesting it is not a sensitive thyroid inhibitor in fish. Overall, we show that unlike in mammals, hyperthyroid conditions in goldfish do not lead to an increased desire or need to consume food, furthering evidence for a weak link between the thyroid and appetite.

Roles for the gut microbiota in regulating neuronal feeding circuits.

The gut microbiota has the capacity to affect host appetite via intestinal satiety pathways, as well as complex feeding behaviors. In this Review, we highlight recent evidence that the gut microbiota can modulate food preference across model organisms. We discuss effects of the gut microbiota on the vagus nerve and brain regions including the hypothalamus, mesolimbic system, and prefrontal cortex, which play key roles in regulating feeding behavior. Crosstalk between commensal bacteria and the central and peripheral nervous systems is associated with alterations in signaling of neurotransmitters and neuropeptides such as dopamine, brain-derived neurotrophic factor (BDNF), and glucagon-like peptide-1 (GLP-1). We further consider areas for future research on mechanisms by which gut microbes may influence feeding behavior involving these neural pathways. Understanding roles for the gut microbiota in feeding regulation will be important for informing therapeutic strategies to treat metabolic and eating disorders.