Suppression Of Food Consumption Research Articles

Does exposure to zinc, methomyl and perfluorooctanoic acid alter feeding behaviour on MUG® in the freshwater amphipod Gammarus fossarum?

Feeding rate alteration is one of the first observed responses when animals are exposed to toxic stress and recognized as relevant tool for studying chemical compounds toxicity. However, food substrate that are currently used for ecotoxicity tests are not always easily available compared to referenced products. Using the European freshwater amphipod Gammarus fossarum, we here proposed for ecotoxicity tests a standardized food substrate fabricated with referenced ingredients: the MUG® (Meal Unit for Gammarid). To investigate the suitability of using MUG® to study behavioural response of amphipods to toxic stress, we explored in laboratory-controlled conditions whether three chemical compounds belonging to different families of contaminants (zinc (Zn): metal; methomyl (MT): insecticide; perfluorooctanoic acid (PFOA): Per-/poly-fluoroalkyl substance (PFAS)) could affect gammarids feeding rates on MUG®. First, we explored the effects of 7-day exposure to different concentrations of each contaminant alone. While PFOA did not affect feeding rate, zinc induced feeding behaviour on MUG® at lower concentration but inhibited food consumption at higher ones, whereas methomyl decreased feeding rate with increased concentration. Then, we explored effects when gammarids were exposed during 7 days to mixtures of molecules in pairs. No effect of mixtures was observed on MUG® consumption compared to control group. Observed effects of binary mixtures were also compared to predicted values based on additive effects of contaminants. Both Zn/MT and Zn/PFOA mixtures inhibited feeding behaviour compared to predictions, resulting in feeding rate values similar to control ones. Overall, our study supports that MUG® represent a promising standardized food substrate for evaluating substances effects on amphipods behaviour during laboratory ecotoxicological bioassays.

Distinct basal forebrain-originated neural circuits promote homoeostatic feeding and suppress hedonic feeding in male mice.

Feeding behaviour is influenced by two primary factors: homoeostatic needs driven by hunger and hedonic desires for pleasure even in the absence of hunger. While efficient homoeostatic feeding is vital for survival, excessive hedonic feeding can lead to adverse consequences such as obesity and metabolic dysregulations. However, the neurobiological mechanisms that orchestrate homoeostatic versus hedonic food consumption remain largely unknown. Here we show that GABAergic proenkephalin (Penk) neurons in the diagonal band of Broca (DBB) of male mice respond to food presentation. We further demonstrate that a subset of DBBPenk neurons that project to the paraventricular nucleus of the hypothalamus are preferentially activated upon food presentation during fasting periods and transmit a positive valence to facilitate feeding. On the other hand, a separate subset of DBBPenk neurons that project to the lateral hypothalamus are preferentially activated when detecting a high-fat high-sugar (HFHS) diet and transmit a negative valence to inhibit food consumption. Notably, when given free choice of chow and HFHS diets, mice with the whole DBBPenk population ablated exhibit reduced consumption of chow but increased intake of the HFHS diet, resulting in accelerated development of obesity and metabolic disturbances. Together, we identify a molecularly defined neural population in male mice that is crucial for the maintenance of energy balance by facilitating homoeostatic feeding while suppressing hedonic overeating.

Intracerebroventricular prokineticin 2 infusion may play a role on the hypothalamus-pituitary-thyroid axis and energy metabolism

The hypothesis of this study is to determine the effects of intracerebroventricular (icv) prokineticin 2 infusion on food consumption and body weight and to elucidate whether it has effects on energy expenditure via the hypothalamus-pituitary-thyroid (HPT) axis in adipose tissue. A total of 40 rats were used in the study and 4 groups were established: Control, Sham, Prokineticin 1.5 and Prokineticin 4.5 (n=10). Except for the Control group, rats were treated intracerebroventricularly via osmotic minipumps, the Sham group was infused with aCSF (vehicle), and the Prokineticin 1.5 and Prokineticin 4.5 groups were infused with 1.5 nMol and 4.5 nMol prokineticin 2, respectively. Food and water consumption and body weight were monitored during 7-day infusion in all groups. At the end of the infusion, the rats were decapitated and serum TSH, fT4 and fT3 levels were determined by ELISA. In addition, PGC-1α and UCP1 gene expression levels in white adipose tissue (WAT) and brown adipose tissue (BAT), TRH from rat hypothalamic tissue were determined by real-time PCR. Icv prokineticin 2 (4.5 nMol) infusion had no effect on water consumption but reduced daily food consumption and body weight (p<0.05). Icv prokineticin 2 (4.5 nMol) infusion significantly increased serum TSH, fT4 and fT3 levels when compared to Control and Sham groups (p<0.05). Also, icv prokineticin 2 (4.5 nMol) infusion increased the expression of TRH in the hypothalamus tissue and expression of PGC-1α UCP1 in the WAT and BAT (p<0.05). Icv prokineticin 2 (4.5 nMol) infusion may suppress food consumption via its receptors in the hypothalamus and reduce body weight by stimulating energy expenditure and thermogenesis in adipose tissue through the HPT axis.

Effect of short neuropeptide F signaling on larval feeding in Mythimna separata.

Mythimna separata is a notorious phytophagous pest which poses serious threats to cereal crops owing to the gluttony of the larvae. Because short neuropeptide F (sNPF) and its receptor sNPFR are involved in a diversity of physiological functions, especially in functions related to feeding in insects, it is a molecular target for pest control. Herein, an sNPF and 2 sNPFRs were identified and cloned from M. separata. Bioinformatics analysis revealed that the sNPF and its receptors had a highly conserved RLRFamide C-terminus and 7 transmembrane domains, respectively. The sNPF and its receptor genes were distributed across larval periods and tissues, but 2 receptors had distinct expression patterns. The starvation-induced assay elucidated that sNPF and sNPFR expression levels were downregulated under food deprivation and recovered with subsequent re-feeding. RNA interference knockdown of sNPF, sNPFR1, and sNPFR2 by injection of double-stranded RNA into larvae not only suppressed food consumption and increased body size and weight, but also led to decrease of glycogen and total lipid contents, and increase of trehalose compared with double-stranded green fluorescent protein injection. Furthermore, molecular docking was performed on the interaction mode between sNPFR protein and its ligand sNPF based on the 3-dimensional models constructed by AlphaFold; the results indicated that both receptors were presumably activated by the mature peptide sNPF-2. These results revealed that sNPF signaling played a considerably vital role in the feeding regulation of M. separata and represents a potential control target for this pest.

Abamectin induces mortality, inhibits food consumption, and causes histological changes in the midgut of the velvetbean caterpillar Anticarsia gemmatalis (Lepidoptera: Noctuidae)

Abamectin induces mortality, inhibits food consumption, and causes histological changes in the midgut of the velvetbean caterpillar Anticarsia gemmatalis (Lepidoptera: Noctuidae)

Albumin-binding DARPins as scaffold improve the hypoglycemic and anti-obesity effects of exendin-4 in vivo

Type 2 diabetes mellitus (T2DM) and obesity have been considered epidemics and threats to public health worldwide. Exendin-4 (Ex), a GLP-1R agonist, has potential for treating T2DM and obesity. However, Ex has a half-life of only 2.4 h in humans and needs to be administered twice daily, which hampers its clinical application. In this study, we synthesized four new GLP-1R agonists by genetically fusing Ex to the N-terminus of HSA-binding ankyrin repeat proteins (DARPins) via linkers of different lengths, denoted as Ex-DARPin-GSx fusion proteins (x = 0, 1, 2, and 3). The Ex-DARPin fusion proteins were substantially stable, resulting in incomplete denaturation even at 80°C. The in vitro bioactivity results demonstrated that Ex-DARPin fusion proteins could bind to HSA and activate GLP-1R. The Ex-DARPin fusion proteins had a comparable half-life (29-32 h), which is much longer than that of native Ex (0.5 h in rats). Subcutaneous injection of 25 nmol/kg Ex-DARPin fusion protein normalized blood glucose (BG) levels for at least 72 h in mice. The Ex-DARPin fusion proteins, injected at 25 nmol/kg every three days, significantly lowered BG, inhibited food consumption, and reduced body weight (BW) for 30 days in STZ-induced diabetic mice. Histological analysis of pancreatic tissues using H&E staining revealed that Ex-DARPin fusion proteins significantly improved the survival of pancreatic islets in diabetic mice. The differences in in vivo bioactivity of fusion proteins with different linker lengths were not significant. According to the findings in this study, long-acting Ex-DARPin fusion proteins designed by us hold promise for further development as antidiabetic and antiobesity therapeutic agents. Our findings also indicate that DARPins are a universal platform for generating long-acting therapeutic proteins via genetic fusion, thus broadening the application scope of DARPins.

Pathway-specific GABAergic inhibition contributes to the gain of resilience against anorexia-like behavior of adolescent female mice.

Anorexia nervosa is one of the most debilitating mental illnesses that emerges during adolescence, especially among females. Anorexia nervosa is characterized by severe voluntary food restriction and compulsive exercising, which combine to cause extreme body weight loss. We use activity-based anorexia (ABA), an animal model, to investigate the neurobiological bases of vulnerability to anorexia nervosa. This is a Mini-Review, focused on new ideas that have emerged based on recent findings from the Aoki Lab. Our findings point to the cellular and molecular underpinnings of three ABA phenomena: (1) age-dependence of ABA vulnerability; (2) individual differences in the persistence of ABA vulnerability during adolescence; (3) GABAergic synaptic plasticity in the hippocampus and the prefrontal cortex that contributes to the suppression of the maladaptive anorexia-like behaviors. We also include new data on the contribution to ABA vulnerability by cell type-specific knockdown of a GABA receptor subunit, α4, in dorsal hippocampus. Although the GABA system recurs as a key player in the gain of ABA resilience, the data predict why targeting the GABA system, singularly, may have only limited efficacy in treating anorexia nervosa. This is because boosting the GABAergic system may suppress the maladaptive behavior of over-exercising but could also suppress food consumption. We hypothesize that a sub-anesthetic dose of ketamine may be the magic bullet, since a single injection of this drug to mid-adolescent female mice undergoing ABA induction enhances food consumption and reduces wheel running, thereby reducing body weight loss through plasticity at excitatory synaptic inputs to both excitatory and inhibitory neurons. The same treatment is not as efficacious during late adolescence but multiple dosing of ketamine can suppress ABA vulnerability partially. This caveat underscores the importance of conducting behavioral, synaptic and molecular analyses across multiple time points spanning the developmental stage of adolescence and into adulthood. Since this is a Mini-Review, we recommend additional literature for readers seeking more comprehensive reviews on these subjects.

Somatodendritic Release of Cholecystokinin Potentiates GABAergic Synapses Onto Ventral Tegmental Area Dopamine Cells

Neuropeptides are contained in nearly every neuron in the central nervous system and can be released not only from nerve terminals but also from somatodendritic sites. Cholecystokinin (CCK), among the most abundant neuropeptides in the brain, is expressed in the majority of midbrain dopamine neurons. Despite this high expression, CCK function within the ventral tegmental area (VTA) is not well understood. We confirmed CCK expression in VTA dopamine neurons through immunohistochemistry and in situ hybridization and detected optogenetically induced CCK release using an enzyme-linked immunosorbent assay. To investigate whether CCK modulates VTA circuit activity, we used whole-cell patch clamp recordings in mouse brain slices. We infused CCK locally invivo and tested food intake and locomotion in fasted mice. We also used invivo fiber photometry to measure Ca2+ transients in dopamine neurons during feeding. Here we report that VTA dopamine neurons release CCK from somatodendritic regions, where it triggers long-term potentiation of GABAergic (gamma-aminobutyric acidergic) synapses. The somatodendritic release occurs during trains of optogenetic stimuli or prolonged but modest depolarization and is dependent on synaptotagmin-7 and T-type Ca2+ channels. Depolarization-induced long-term potentiation is blocked by a CCK2 receptor antagonist and mimicked by exogenous CCK. Local infusion of CCK invivo inhibits food consumption and decreases distance traveled in an open field test. Furthermore, intra-VTA-infused CCK reduced dopamine cell Ca2+ signals during food consumption after an overnight fast and was correlated with reduced food intake. Our experiments introduce somatodendritic neuropeptide release as a previously unknown feedback regulator of VTA dopamine cell excitability and dopamine-related behaviors.

Olfactory Senses Modulate Food Consumption and Physiology in Drosophila melanogaster.

Both sensory and metabolic processes guide food intake. Olfactory inputs help coordinate food appreciation and selection, but their role in food consumption and post-feeding physiology remains poorly understood. In this study, using Drosophila melanogaster as a model system, we investigated the effects of olfactory sensory neurons (OSNs) on food consumption, metabolism, and stress responses. We found that dysfunction of OSNs affects diverse processes, including decreased food consumption, increased triacylglycerol level, enhanced stress resistance to starvation or desiccation, and decreased cold resistance. Decreased neuropeptide F receptor (NPFR) level or increased insulin activity in OSNs inhibited food consumption, while impaired NPF signaling or insulin signaling in OSNs increased resistance to starvation and desiccation. These studies provide insights into the function of the olfactory system in control of feeding behaviors and physiology.

DNA methylation-modifiers reduced food intake in juvenile chickens (Gallus gallus) and Japanese quail (Coturnix japonica)

S-Adenosylmethionine (SAM) is the major endogenous methyl donor for methyltransferase reactions, while 5-Azacytidine (AZA) is a synthetic drug inhibiting DNA methyltransferase activity. Both molecules can thus influence DNA methylation patterns in an organism and thereby affect gene expression and ultimately behavior in the long-term. Whether or not effects on behavior are exerted on a shorter time scale is unclear. The goal of this study was to explore the direct effects of SAM and AZA on appetite regulation, using broiler chicken and Japanese quail as the animal models. Fed or 180min-fasted broilers (at day 4 post-hatch) or 360min-fasted quail (at day 7 post-hatch) were intracerebroventricularly injected with SAM or AZA and food intake was measured for 360min. For broilers, there was no effect of AZA, at any dose, on food intake in either fed or fasted chicks at any time point. In contrast, 1 and 10µg doses of SAM reduced food intake in fed chicks at 60min post-injection. In fasted chicks, although there were no differences for the first 30min post-injection, SAM suppressed food intake during the second 30-min period. For quail, however, AZA (25µg dose) decreased food intake at 60 and 150-360min post-injection in fasted birds. A reduction in food intake was also observed at 120- and 360-min post-injection in fed quail in response to 5 and 25µg doses of AZA, respectively. SAM had no effect when quail were fasted, whereas 1µg dose of SAM suppressed food consumption in fed quail during the third 30-min period. Thus, when administered directly into the central nervous system, SAM may act as a transient appetite suppressant in both broilers and quail, whereas the direct inhibitory effect of AZA on food consumption depends on species and nutritional states.

Phytochemical Screening and Bioactivity of Ludwigia spp. in the Control of Plutella xylostella (Lepidoptera: Plutellidae).

Simple SummaryLudwigia species have several pharmacological applications, but their insecticidal proprieties have not been tested. This research thus aimed to study the effects of aqueous extracts on the biological characteristics of Plutella xylostella. We noted that the L. tomentosa, L. longifolia and L. sericea extracts were active. These species showed the best results regarding their ability to control P. xylostella populations, due to the presence of substances that inhibit food consumption and interfere in the morphological and physiological transformations of the offspring and adult oviposition.We tested the bioactivity of aqueous extracts of Ludwigia spp. (Myrtales: Onagraceae) on the biological cycle of Plutella xylostella. We assessed the duration of and viability during the larval, pupal and adult phases, as well as the influence of the extracts on the fecundity and hatching of P. xylostella eggs. Subsequently, we phytochemically screened the extracts. The extracts of L. tomentosa and L. longifolia reduced the pupal weight instead of prolonging the larval stage of P. xylostella. The L. tomentosa effect caused higher larval mortality and reduced the fecundity and hatching of P. xylostella eggs, and L. sericea reduced the egg survival. The phenolic compounds—flavonoids, condensed tannins and alkaloids—were more abundant in L. nervosa, L. tomentosa, L. sericea and L. longifolia. The L. tomentosa, L. longifolia and L. sericea extracts were bioactive, and these species showed the best results regarding their ability to control P. xylostella populations, because these plants produce substances able to inhibit food consumption and interfere with the morphological and physiological transformations of the offspring and the oviposition of adults.

Elafin inhibits obesity, hyperglycemia, and liver steatosis in high-fat diet-treated male mice

Elafin is an antimicrobial and anti-inflammatory protein. We hypothesize that elafin expression correlates with diabetes. Among non-diabetic and prediabetic groups, men have significantly higher serum elafin levels than women. Men with type 2 diabetes mellitus (T2DM) have significantly lower serum elafin levels than men without T2DM. Serum elafin levels are inversely correlated with fasting blood glucose and hemoglobin A1c levels in men with T2DM, but not women with T2DM. Lentiviral elafin overexpression inhibited obesity, hyperglycemia, and liver steatosis in high-fat diet (HFD)-treated male mice. Elafin-overexpressing HFD-treated male mice had increased serum leptin levels, and serum exosomal miR181b-5p and miR219-5p expression. Transplantation of splenocytes and serum exosomes from elafin-overexpressing HFD-treated donor mice reduced food consumption and fat mass, and increased adipose tissue leptin mRNA expression in HFD-treated recipient mice. Elafin improved leptin sensitivity via reduced interferon-gamma expression and induced adipose leptin expression via increased miR181b-5p and miR219-5p expression. Subcutaneous and oral administration of modified elafin inhibited obesity, hyperglycemia, and liver steatosis in the HFD-treated mice. Circulating elafin levels are associated with hyperglycemia in men with T2DM. Elafin, via immune-derived miRNAs and cytokine, activates leptin sensitivity and expression that subsequently inhibit food consumption, obesity, hyperglycemia, and liver steatosis in HFD-treated male mice.

The timing of fasting leads to different levels of food consumption and PYY3-36 in nocturnal mice.

The daily circadian cycle is known to modulate both feeding behavior and metabolism. As such, the timing of food consumption can play a role in regulating overall health. The purpose of this study is to determine whether fasting at different times of the day alters subsequent food consumption and levels of PYY3-36, a hormone secreted after a meal which inhibits appetite. Separate groups of mice were fasted at different times of the day: (1) start of the day, (2) middle of the day, (3) start of the night, and (4) middle of the night, and either injected with vehicle or PYY3-36 to assess their subsequent food consumption patterns, PYY3-36 levels, and glucose and insulin levels. We also investigated whether light exposure during the night would alter food consumption and PYY3-36 levels after fasting. Mice fasted during the start of the daytime exhibited increased food consumption post-fast compared to mice fasted during the night. Injections of PYY3-36 during the night were more effective in reducing food consumption compared to PYY3-36 administration during the day. Constant light exposure suppressed food consumption after fasting and increased fasting PYY3-36 levels. These results indicate that mice exhibit distinct food consumption patterns after being presented with a fast at different times of the day. Light exposure also modulates both food consumption after a fast and levels of PYY3-36.

Effect of intranasal administration of neuropeptide Y and single prolonged stress on food consumption and body weight in male rats

Emerging evidence indicates that intranasal delivery of neuropeptide Y (NPY) to the brain has therapeutic potential for management of stress-triggered neuropsychiatric disorders. Here we aimed to determine how intranasal administration of NPY, either before or immediately after, traumatic stress in single prolonged stress (SPS) rodent model of Post-traumatic stress disorder (PTSD) impacts food consumption and body weight. SPS stressors suppressed food consumption for at least two days in the vehicle-treated animals. When given prior to SPS stressors, intranasal NPY prevented the SPS-elicited reduction in food intake only for several hours afterwards. When given after the SPS stressors, under conditions shown to prevent behavioral and biochemical impairments, intranasal NPY had no effect on food intake. Although all groups showed circadian variation, the SPS-exposed rats ate less than unstressed animals during the dark (active) phase. Seven days after exposure to SPS stressors, there were no differences in food intake, although body weight was still lower than unstressed controls in all the experimental groups. Thus, traumatic stress has pronounced effect on food consumption during the rodent's active phase, and a prolonged effect on body weight. Single intranasal infusion of NPY, which was previously shown to prevent development of several PTSD associated behavioral and neuroendocrine impairments, did not elicit prolonged changes in stress triggered food consumption nor regulation of body weight.

Caffeine Modulates Food Intake Depending on the Context That Gives Access to Food: Comparison With Dopamine Depletion

Caffeine is a methylxanthine consumed in different contexts to potentiate alertness and reduce fatigue. However, caffeine can induce anxiety at high doses. Caffeine is also a minor psychostimulant that seems to act as an appetite suppressant, but there are also reports indicating that it could stimulate appetite. Dopamine also is involved in food motivation and in behavioral activation. In the present series of experiments, we evaluated the effects of acute administration of caffeine on food consumption under different access conditions. CD1 male adult mice had access to highly palatable food (50% sucrose) in a restricted but habitual context, under continuous or intermittent access as well as under anxiogenic, or effortful conditions. Caffeine (2.5–20.0 mg/kg) increased intake at the highest dose under familiar continuous and intermittent access. However, this high dose reduced food intake in the dark-light paradigm. In contrast, a dopamine-depleting agent, tetrabenazine (TBZ; 1.0–8.0 mg/kg) did not affect food intake in any of those experimental conditions. In the T-maze-barrier task that evaluates seeking and taking of food under effortful conditions, caffeine (10.0 mg/kg) decreased latency to reach the food, but did not affect selection of the high-food density arm that required more effort, or the total amount of food consumed. In contrast, TBZ (4.0 mg/kg) reduced selection of the high food density arm with the barrier, thus affecting amount of food consumed. Interestingly, a small dose of caffeine (5.0 mg/kg) was able to reverse the anergia-inducing effects produced by TBZ in the T-maze. These results suggest that caffeine can potentiate or suppress food consumption depending on the context. Moreover, caffeine did not change appetite, and did not impair orientation toward food under effortful conditions, but it rather helped to achieve the goal by improving speed and by reversing performance to normal levels when fatigue was induced by dopamine depletion.

Investigations into Tissue Distribution and Inhibition of Food Consumption with Efpeglenatide

Efpeglenatide (efpeg), a long-acting glucagon-like peptide-1 receptor agonist in development for type 2 diabetes, induces weight loss through satiety and reduced food intake. Studies in Sprague Dawley rats investigated how peripheral and central mechanisms contribute to the anorectic effects of efpeg. Tissue distribution of efpeg was assessed by whole-body autoradioluminography with 14C-efpeg. The contribution of vagal nerve signaling to food intake control was assessed in vagotomized rats treated with exenatide (0.15 or 0.45 nmol/kg twice daily) or efpeg (0.71 or 2.1 nmol/kg every 2 days). Pharmacokinetic parameters and mean radioactivity of 14C-efpeg in selected organs/tissues are shown in Figure. Peak concentration (Cmax) of 14C-efpeg was highest in the kidney cortex; Cmax at all other sites was similar to/lower than in blood, relatively high in the intestine and pituitary, with below-quantifiable levels in the cerebellum/cerebrum. Inhibition of food intake was not attenuated in vagotomized vs. sham-operated rats at higher doses of efpeg (3-day cumulative intake: 47.4 vs. 49.4 g) or exenatide (54.9 vs. 60.7 g), suggesting a non-vagal mechanism for these anorectic effects. These findings suggest that central mechanisms are involved in the anorectic effects of efpeg in this animal model; potential cell-signaling effects of efpeg in the intestine and pituitary need to be investigated further. Disclosure Y. Park: Employee; Self; Hanmi Pharmaceutical. Stock/Shareholder; Self; Hanmi Pharmaceutical. I. Choi: Employee; Self; Hanmi Pharmaceutical. Stock/Shareholder; Self; Hanmi Pharmaceutical. M.E. Trautmann: Consultant; Self; ProSciento. Stock/Shareholder; Self; Eli Lilly and Company. Consultant; Self; Hanmi Pharmaceutical, CeQur Corporation, Intarcia Therapeutics, Inc., Servier. M. Hompesch: Other Relationship; Self; Hanmi Pharmaceutical. C.H. Sorli: Employee; Self; Sanofi.

Peripherally injected ghrelin and leptin reduce food hoarding and mass gain in the coal tit (Periparus ater).

In birds little is known about the hormonal signals that communicate nutritional state to the brain and regulate appetitive behaviours. In mammals, the peptide hormones ghrelin and leptin elevate and inhibit consumption and food hoarding, respectively. But in birds, administration of both ghrelin and leptin inhibit food consumption. The role of these hormones in the regulation of food hoarding in avian species has not been examined. To investigate this, we injected wild caught coal tits (Periparus ater) with leptin, high-dose ghrelin, low-dose ghrelin and a saline control in the laboratory. We then measured food hoarding and mass gain, as a proxy of food consumption, every 20 min for 2 h post-injection. Both high-dose ghrelin and leptin injections significantly reduced hoarding and mass gain compared with controls. Our results provide the first evidence that hoarding behaviour can be reduced by both leptin and ghrelin in a wild bird. These findings add to evidence that the hormonal control of food consumption and hoarding in avian species differs from that in mammals. Food hoarding and consumptive behaviours consistently show the same response to peripheral signals of nutritional state, suggesting that the hormonal regulation of food hoarding has evolved from the consumption regulatory system.

Pranlukast; An Alternative Potential Leptin Stimulator: Structure-Based Virtual Screening Study

Background: Leptin is secreted by adipocytes, transported into the brain and binds to its receptor in the hypothalamus, and activates JAK-STAT3, leading to increase in “anorexigenic peptides” which normally inhibit food consumption and reduce weight.Objectives: In the current study, a hybrid approach of molecular docking and virtual screening was performed, for the identification of active alternative compounds to manage obesity disorders.Methods: Screening was performed using structure-based drug design against approved FDA drugs; molecular modeling was done using AutoDockVina; only top 10 conformers’ ligands with highest and best scores were selected. In order to increase the likelihood of successful docking, in silico Virtual Screening (VS) of selected compounds were filtered according to their molecular weight and partition coefficient; a molecular weight of less than 500 and a partitioning coefficient (log P) of less than 5 filtering is applied.Result: Here, we report the screening of four compounds that have showed maximum binding affinity against Leptin receptor, obtained through the ZINC database. A VS approach coupled with docking energies illustrated that Pranlukast could be potential stimulator compounds for targeting Leptin receptor.Conclusion: We proposed that Pranlukast may be more potent Leptin receptor stimulator analogue based on the binding energy values. Further work can be extended to study the receptor ligand interactions experimentally and evaluation of their biological activity would help in designing novel therapeutic lead for the management of obesity disorders.

Modulation of food consumption and sleep–wake cycle in mice by the neutral CB1 antagonist ABD459

The brain endocannabinoid system is a potential target for the treatment of psychiatric and metabolic conditions. Here, a novel CB1 receptor antagonist (ABD459) was synthesized and assayed for pharmacological efficacy in vitro and for modulation of food consumption, vigilance staging and cortical electroencephalography in the mouse. ABD459 completely displaced the CB1 agonist CP99540 at a Ki of 8.6 nmol/l, and did not affect basal, but antagonized CP55940-induced GTPγS binding with a KB of 7.7 nmol/l. Acute ABD459 (3-20 mg/kg) reliably inhibited food consumption in nonfasted mice, without affecting motor activity. Active food seeking was reduced for 5-6 h postdrug, with no rebound after washout. Epidural recording of electroencephalogram confirmed that ABD459 (3 mg/kg) robustly reduced rapid eye movement (REM) sleep, with no alterations of wakefulness or non-REM sleep. Effects were strongest during 3 h postdrug, followed by a progressive washout period. The CB1 antagonist AM251 (3 mg/kg) and agonist WIN-55,212-2 (WIN-2: 3 mg/kg) also reduced REM, but variously affected other vigilance stages. WIN-2 caused a global suppression of normalized spectral power. AM251 and ABD459 lowered delta power and increased power in the theta band in the hippocampus, but not the prefrontal cortex. The neutral antagonist ABD459 thus showed a specific role of endocannabinoid release in attention and arousal, possibly through modulation of cholinergic activity.

Agmatine attenuates hyperactivity and weight loss associated with activity-based anorexia in female rats

Anorexia nervosa is a debilitating eating disorder characterized by hypophagia, body weight loss, amenorrhea and intense fear of weight gain. In present study, the effect of subchronic agmatine treatment on development of activity based anorexia (ABA) in female rats has been investigated. Animals were injected with saline or agmatine (10-40 mg/kg, ip) just before the onset of dark phase and shifted to experimental cage with wheel for ABA test for 10days. A pre-weighed quantity of food pellets (10g) was placed daily for a restricted period of only 2h (1700-1900h) and food intake was monitored (g) manually by weighing the leftover food. Rats restricted to ABA paradigm, showed greater wheel running, suppressed food consumption, disrupted estrous cycle and weight loss. On the other hand, subchronic agmatine (10-40mg/kg, ip, for 10days) treatment decreased wheel running activity, pronounced increased in food intake and restored body weights as compared to saline treated animals. Further, agmatine treatment decreased corticosterone levels in ABA rats, thereby stabilizing HPA axis in ABA rats. Subchronic agmatine treatment also prevented the disruptions of estrous cycle. Considering the common resistance of anorexia nervosa to current pharmacotherapy, the preliminary data on reduction of physical activity by agmatine, may have potential therapeutic importance. Thus, the role of agmatine in feeding behavior is likely to provide insight into the circumstances that facilitate treatment in eating disorders like anorexia nervosa.