Appetite Regulation Research Articles

Efficiency of post-meal memory inhibition predicts subsequent food intake

Memory processes may contribute to appetite regulation. When people look at palatable foods, their desire to consume them depends upon memory retrieval (i.e., recalling if it will taste good). If memory inhibition occurs during satiety, then pleasant eating-related memories will not be retrieved, making eating less likely. In contrast, if memory inhibition is less efficient, pleasant food-related memories will be retrieved, the food will appear desirable, and the chance of consumption increases. Here we tested whether a putative measure of memory inhibition could predict post-meal snack food intake. Study participants looked at palatable snacks and judged their desire to eat them (i.e., a memory-dependent process), and then ate a small sample of each food, and rated them for liking (i.e., an orosensory-dependent process) – all using category rating scales. Following a filling meal, this test was repeated, alongside others. Finally, participants were given the opportunity for ad libitum snack food consumption, in addition to collecting measures such as impulsivity. Poorer memory inhibition (i.e., smaller changes in wanting relative to liking from pre-to post-meal) was associated with greater consumption of snacks on the ad libitum test (Sr2% = 4.4, p = 0.006) after controlling for other variables likely to influence eating (e.g., impulsivity). This effect was maintained even when the memory inhibition measure was based on foods different to those being consumed on the ad libitum snacking test. In conclusion, memory inhibition may contribute to food intake regulation, and when this is less efficient, more palatable food is likely to be eaten in the post-meal period.

The Role of Public Health in Preventing Obesity

Obesity has become a global public health crisis, affecting individuals across various demographics and leading to significant health and economic burdens. This paper investigates the role of public health interventions in preventing obesity, focusing on epidemiological trends, genetic and environmental factors, and community-based approaches. The review analyzes the intersection of genetics, appetite regulation, and the environment in obesity’s etiology while emphasizing the need for multidisciplinary, evidence-based, and community-driven interventions. Public health policies, including legislative measures, public awareness campaigns, and school-based programs, are crucial in combating obesity and promoting healthier lifestyles. Effective obesity prevention requires holistic, inclusive, and culturally sensitive strategies that engage communities, prioritize early intervention, and foster sustainable lifestyle changes. Keywords: Obesity prevention, public health, epidemiology, gene-environment interaction.

Rediscovering a Forgotten Link: TSPO and RIM-BP1 in Appetite Regulation.

The translocator protein of 18 kDa (TSPO) and RIM binding protein 1 (RIM-BP1) are both heavily expressed in neurons at the olfactory bulb. These proteins have overlapping functional profiles and are both implicated in the development of obesity. Over 20 years ago, a yeast 2-hybrid experiment discovered that RIM-BP1 interacts with a peptide constructed from a fraction of the TSPO sequence. Considering these data, the authors predict that the interaction between RIM-BP1 and TSPO could alter the olfactory system's mediation of appetite. Despite the therapeutic potential of this interaction, it has never been confirmed if the full TSPO protein and RIM-BP1 interact. The interaction is instead often cited as physiologically irrelevant. This commentary revisits the forgotten interaction between TSPO and RIM-BP1, reviewing all relevant literature discussing their relationship. Contrary to common discourse that the RIM-BP1 and TSPO are potential binding partners, while the interaction may regulate many neurological functions, existing evidence suggests that the interaction would have a specific role in odor-guided appetite. Further research into the nutritional neuroscientific consequences of TSPO/RIM-BP1 interactions should therefore be conducted.

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.

Hunger, Satiety, and Their Vulnerabilities.

The psychological states of hunger and satiety play an important role in regulating human food intake. Several lines of evidence suggest that these states rely upon declarative learning and memory processes, which are based primarily in the medial temporal lobes (MTL). The MTL, and particularly the hippocampus, is unusual in that it is especially vulnerable to insult. Consequently, we examine here the impact on hunger and satiety of conditions that: (1) are central to ingestive behaviour and where there is evidence of MTL pathology (i.e., habitual consumption of a Western-style diet, obesity, and anorexia nervosa); and (2) where there is overwhelming evidence of MTL pathology, but where ingestive behaviour is not thought central (i.e., temporal lobe epilepsy and post-traumatic stress disorder). While for some of these conditions the evidence base is currently limited, the general conclusion is that MTL impairment is linked, sometimes strongly, to dysfunctional hunger and satiety. This focus on the MTL, and declarative learning and memory processes, has implications for the development of alternative treatment approaches for the regulation of appetite.

Molecular mechanism of prolactin-releasing peptide recognition and signaling via its G protein-coupled receptor

Prolactin-releasing peptide (PrRP) is an RF-amide neuropeptide that binds and activates its cognate G protein-coupled receptor, prolactin-releasing peptide receptor (PrRPR), also known as GPR10. PrRP and PrRPR are highly conserved across mammals and involved in regulating a range of physiological processes, including stress response, appetite regulation, pain modulation, cardiovascular function, and potentially reproductive functions. Here we present cryo-electron microscopy structures of PrRP-bound PrRPR coupled to Gq or Gi heterotrimer, unveiling distinct molecular determinants underlying the specific recognition of the ligand’s C-terminal RF-amide motif. We identify a conserved polar pocket that accommodates the C-terminal amide shared by RF-amide peptides. Structural comparison with neuropeptide Y receptors reveals both similarities and differences in engaging the essential RF/RY-amide motifs. Our findings demonstrate the general mechanism governing RF-amide motif recognition by PrRPR and RF-amide peptide receptors, and provide a foundation for elucidating activation mechanisms and developing selective drugs targeting this important peptide–receptor system.

Effects of Polyunsaturated Fatty Acid/Saturated Fatty Acid Ratio and Different Amounts of Monounsaturated Fatty Acids on Adipogenesis in 3T3-L1 Cells.

(1) Background: Adipose tissue serves as a central repository for energy storage and is an endocrine organ capable of secreting various adipokines, including leptin and adiponectin. These adipokines exert profound influences on diverse physiological processes such as insulin sensitivity, appetite regulation, lipid metabolism, energy homeostasis, and body weight. Given the integral role of adipose tissue in metabolic regulation, it is imperative to investigate the effects of varying proportions and types of dietary fats on adipocyte function. In addition, our previous study showed that P/S = 5 and MUFA = 60% appeared to be beneficial in preventing white adipose tissue accumulation by decreasing plasma insulin levels and increasing hepatic lipolytic enzyme activities involved in β-oxidation. Therefore, the objective of this study was to explore the effects of a polyunsaturated fatty acid (PUFA) to saturated fatty acid (SFA) ratio of 5 and varying levels of monounsaturated fatty acids (MUFA = 30% or 60%) on lipogenesis. (2) Methods: We cultured 3T3-L1 mouse embryo fibroblasts in Dulbecco's modified Eagle's medium (DMEM) containing 10% bovine calf serum until confluent. Varying ratios of palmitic acid (PA), oleic acid (OA), and linoleic acid (LA) were first bound with bovine serum albumin (BSA) before being applied to 3T3-L1 adipocytes in low doses and in high doses. (3) Results: Low doses of P/S ratio = 5, MUFA = 60% (M60) fatty acids decreased the accumulation of triglycerides in mature adipocytes by decreasing the mRNA expression of adipogenic factors, such as peroxisome proliferator-activated receptors (PPARs), lipoprotein lipase (LPL), and glucose transporter-4 (GLUT-4), while increasing lipolytic enzyme (hormone-sensitive lipase, HSL) expression when compared to high doses of P/S ratio = 5, MUFA = 60% (M60), low and high doses of P/S ratio = 5, MUFA = 30% (M30). Furthermore, the treatment of M60 in low doses also decreased the secretion of leptin and increased the secretion of adiponectin in adipocytes. (4) Conclusions: The composition of P/S = 5, MUFA = 60% fatty acid in low doses appeared to result in anti-adipogenic effects on 3T3-L1 adipocytes due to the down-regulation of adipogenic effects and the transcription factor.

GDF15 Targeting for Treatment of Hyperemesis Gravidarum.

Nausea and vomiting during pregnancy (NVP), particularly its severe form, Hyperemesis gravidarum (HG), affects up to 70% of pregnancies and significantly impacts the quality of life for those with the condition as well as generates a great economic burden, with annual costs exceeding $1.7 billion in the United States. Despite the available treatments targeting neurotransmitters like serotonin and dopamine, many patients experience inadequate relief and suffer from severe side effects, including headaches and dizziness. Recent research has underscored the role of GDF15, a protein mainly produced by the placenta and linked to NVP symptoms. This protein, part of the TGF-β superfamily, has been implicated in appetite and weight regulation and is altered in those with HG due to specific genetic mutations. Addressing the challenges of delivering effective treatments, current innovations focus on targeting GDF15 to reduce symptoms while ensuring fetal safety. Promising therapeutic strategies include non-IgG immunotherapies, small peptide and molecule antagonists, and novel administration methods such as transdermal patches. These approaches aim to optimize dosage and reduce adverse effects. The effective development and testing of these treatments necessitate advanced animal models that closely resemble human pregnancy physiology, highlighting the need for further research and funding. This ongoing research holds significant potential to improve the clinical outcomes for HG patients and decrease the economic impact on healthcare systems, urging a dedicated response from the scientific and medical communities to advance these promising treatments.

Genetic assessment of litter size, body weight, carcass traits and gene expression profiles in exotic and indigenous rabbit breeds: a study on New Zealand White, Californian, and Gabali rabbits in Egypt

Rabbits are essential for commercial meat production due to their efficient growth and productivity, breeds like New Zealand White (NZW), Californian (CAL), and Gabali (GAB) rabbits offer unique genetic traits in litter, growth, and carcass traits. This study aimed to evaluate heritability (h2), genetic and phenotypic correlations (rg and rp) for litter size, body weight and carcass traits across California (CAL), New Zealand white (NZW) and Gabali (GA) rabbits. Along with exploring gene expression profiles of TBC1D1, NPY, AGRP, POMC, Leptin, GH, GHR, IGF-1, CAA, GPR, ACC, CPT1, FAS, and CART in the brain, liver, and meat tissues of different rabbit breeds. The breed genotype had a significant impact on litter size (LS), litter weight (LW), body weight at 12 weeks (BW12), and daily weight gain (DWG) traits. NZW rabbits displayed superior performance in terms of litter size and litter weight, while CAL rabbits recorded the highest values for BW12 and DWG. Heritability estimates (h2) were generally low for litter size (ranging from 0.05 to 0.12) and medium for body weight (ranging from 0.16 to 0.31). Both genetic (rg) and phenotypic (rp) correlations for litter size were positive and moderate (ranging from 0.08 to 0.48), while correlations for body weight ranged from 0.21 to 0.58. Additionally, CAL rabbits exhibited higher carcass traits compared to NZW and GA rabbits. In terms of breed-specific gene expression patterns, New Zealand White (NZW) rabbits displayed the highest expression levels of key genes related to energy metabolism (TBC1D1), appetite regulation (NPY, AGRP, POMC), nutrient transport (CAA), and G protein-coupled receptors (GPR) in both brain and liver tissues. Californian (CAL) rabbits exhibited superior gene expression of the ACC gene in brain tissue and GH, GHR, and IGF-1 genes in brain and meat tissues. Gabali (GAB) rabbits demonstrated the highest expression levels of TBC1D1, NPY, AGRP, GPR, and ACC genes in meat tissues. These breed-specific gene expression differences, combined with genetic evaluation efforts, have the potential to enhance reproductive and productive performance in rabbits, offering valuable insights for rabbit breeding programs and genetic selection.

Microbiome and metabolome analyses indicate variations in the gut microbiota that disrupt regulation of appetite.

The mechanism connecting gut microbiota to appetite regulation is not yet fully understood. This study identifies specific microbial community and metabolites that may influence appetite regulation. In the initial phase of the study, mice were administered a broad-spectrum antibiotic cocktail (ABX) for 10 days. The treatment significantly reduced gut microbes and disrupted the metabolism of arginine and tryptophan. Consequently, ABX-treated mice demonstrated a notable reduction in feed consumption. The hypothalamic expression levels of CART and POMC, two key anorexigenic factors, were significantly increased, while orexigenic factors, such as NPY and AGRP, were decreased. Notably, the levels of appetite-suppressing hormone cholecystokinin in the blood were significantly elevated. In the second phase, control mice were maintained, while the ABX-treated mice received saline, probiotics, and short-chain fatty acids (SCFAs) for an additional 10 days to restore their gut microbiota. The microbiota reconstructed by probiotic and SCFA treatments were quite similar, while microbiota of the naturally recovering mice demonstrated greater resemblance to that of the control mice. Notably, the abundance of Akkermansia and Bacteroides genera significantly increased in the reconstructed microbiota. Moreover, microbiota reconstruction corrected the disrupted arginine and tryptophan metabolism and the abnormal peripheral hormone levels caused by ABX treatment. Among the groups, SCFA-treated mice had the highest feed intake and NPY expression. Our findings indicate that gut microbes, especially Akkermansia, regulate arginine and tryptophan metabolism, thereby influencing appetite through the microbe-gut-brain axis.

Dietary monosodium glutamate affects the growth and feed utilization of Eriocheir sinensis by regulating the appetite related genes expression

This study assessed the impacts of monosodium glutamate (MSG) on the growth performance, feed utilization, feed intake, and appetite regulation of Chinese mitten crab, Eriocheir sinensis. A total of 240 juvenile crabs (9.16 ± 0.21 g) were assigned to six experimental diets supplemented with MSG at 0 %, 0.20 %, 0.39 %, 0.59 %, 0.78 % and 0.98 %. The results demonstrated that 0.59 % MSG supplementation significantly enhanced the weight gain rate (WGR), specific growth rate (SGR), and feed utilization of juvenile E. sinensis by increasing feed intake (FI) (p < 0.05). Moreover, dietary moderate MSG improved the mid-intestine morphology, such as height of microvillus (HMV), width of microvillus (WMV), and thickness of muscularis (TM). The qRT-PCR analysis demonstrated that the mRNA expression levels of the appetite-stimulating neural signals agouti related protein (agrp) and ghrelin were increased significantly by dietary moderate MSG (p < 0.05). Conversely, the mRNA levels of protein kinase B (akt), target of rapamycin (tor) and 4E-binding protein (4e-bp), as well as appetite-suppressing neural signals pro-opiomelanocortin (pomc), corticotropin-releasing factor (crf) and peptide yy (pyy) were significantly down-regulated (p < 0.05). The two-slope broken-line regression analysis of SGR in relation to dietary MSG levels suggested that the optimum dietary MSG level for juvenile E. sinensis was 5.6 g/kg. Collectively, MSG may potentially stimulate or suppress the appetite regulation neural signals/hormones, thereby modulating the feeding behavior of E. sinensis.

Sex-Specific changes in stress circuitry of the nucleus tractus solitarius following food deprivation in two rat strains

Food deprivation is used in many experimental models and is becoming increasingly prevalent in human diets. The impact of food deprivation on specific brain regions, including the nucleus of the tractus solitarius (NTS), a region that is involved in hunger and satiety sensing, remains to be determined. The NTS is a heterogeneous nucleus that includes corticotropin releasing factor receptor 1 (CRF1) neurons. CRF1 is implicated in both stress and appetite regulation, but the effects of food deprivation on CRF1 NTS neurons are unclear. We used immunofluorescence to examine the effects of 24-hour food deprivation on NTS activity in male and female Sprague-Dawley (SD) rats and CRF1-cre rats using cFos, an immediate early gene and neuronal marker of activation. NTS activity was increased in food deprived male but not female SD rats. In food deprived CRF1-cre rats, males had an increased proportion of active CRF1 + neurons with no change in females. In CRF1-cre rats, increased global NTS activity was observed in food deprived and refed males. Activation of CRF1 + neurons was also increased after deprivation but was reduced by refeeding. In females, food deprivation decreased global NTS activity that was then increased by refeeding, while CRF1 activity was unchanged.Collectively, these data suggest the NTS is differentially activated after food deprivation in a sex-specific manner, whereby males are more sensitive than females. These results provide insight into the role of brainstem stress circuitry in changes associated with conditions including intermittent fasting and eating disorders like anorexia.

Enteroendocrine cells regulate intestinal homeostasis and epithelial function

Enteroendocrine cells (EECs) are well-known for their systemic hormonal effects, especially in the regulation of appetite and glycemia. Much less is known about how the products made by EECs regulate their local environment within the intestine. Here, we focus on paracrine interactions between EECs and other intestinal cells as they regulate three essential aspects of intestinal homeostasis and physiology: 1) intestinal stem cell function and proliferation; 2) nutrient absorption; and 3) mucosal barrier function. We also discuss the ability of EECs to express multiple hormones, describe in vitro and in vivo models to study EECs, and consider how EECs are altered in GI disease.

Characterizing Growth-Retarded Japanese Eels (Anguilla japonica): Insights into Metabolic and Appetite Regulation.

During field surveys and culture procedures, large growth disparities in Anguilla japonica have been observed. However, the potential causes are unknown. This study explored differences in digestive ability, metabolic levels, and transcriptomic profiles of appetite-related genes between growth-retarded eel (GRE) and normal-growing eel (NGE) under the same rearing conditions. The results showed that growth hormone (gh) mRNA expression in GREs was considerably lower than NGEs. The levels of total protein (TP), total cholesterol (T-CHO), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), blood ammonia (BA), blood urea nitrogen (BUN), and alkaline phosphatase (ALP) in GREs were significantly lower than in NGEs. Conversely, levels of glucose (GLU), alanine aminotransferase (ALT), and aspartate transaminase (AST) were higher in GREs. The activities of SOD, CAT, and T-AOC levels were also significantly lower in GREs, as were the activities of glucose-related enzymes including hexokinase (HK), pyruvate kinase (PK), phosphoenolpyruvate carboxykinase (PEPCK), and glucose-6-phosphatase (G6PASE). Additionally, orexigenic genes (npy and ghrelin) were dramatically downregulated, whereas anorexigenic genes (crh and pyy) were significantly upregulated in GREs. These findings suggested that variances in growth hormone, metabolic activities, and appetite level could be associated with the different growth rates of A. japonica. The present research not only revealed the characteristics of the growth, metabolism, and appetite of GREs but also offered new perspectives into the substantial growth discrepancies in A. japonica, providing novel ideas for enhancing fish growth.

Exercise-induced appetite suppression: An update on potential mechanisms.

The first systematic reviews of the effects of exercise on appetite-regulation and energy intake demonstrated changes in appetite-regulating hormones consistent with appetite suppression and decreases in subsequent relative energy intake over a decade ago. More recently, an intensity-dependent effect and several potential mechanisms were proposed, and this review aims to highlight advances in this field. While exercise-induced appetite suppression clearly involves acylated ghrelin, glucagon-like peptide-1 may also be involved, though recent evidence suggests peptide tyrosine tyrosine may not be relevant. Changes in subjective appetite perceptions and energy intake continue to be equivocal, though these results are likely due to small sample sizes and methodological inconsistencies. Of the proposed mechanisms responsible for exercise-induced appetite suppression, lactate has garnered the most support through invitro and invivo rodent studies as well as a growing amount of work in humans. Other potential modulators of exercise-induced appetite suppression may include sex hormones, growth-differentiation factor 15, Lac-Phe, brain-derived neurotrophic factor, and asprosin. Research should focus on the mechanisms responsible for the changes and consider these other modulators (i.e., myokines/exerkines) of appetite to improve our understanding of the role of exercise on appetite regulation.

Comprehensive Role of GDF15 in Inhibiting Adipogenesis and Hyperlipidemia, Enhancing Cardiovascular Health and Alleviating Inflammation in Metabolic Disorders.

Growth Differentiation Factor 15 (GDF15) has emerged as a pivotal signaling molecule implicated in diverse physiological processes, spanning metabolic regulation, inflammation, and cardiovascular health. This study provides a comprehensive exploration of GDF15's multifaceted role, primarily focusing on its association with obesity-related complications and therapeutic potential. GDF15's involvement in energy homeostasis, specifically its regulation of body weight and appetite through hindbrain neuron activation and the GFRAL-RET signaling pathway, underscores its significance as an appetite-regulating hormone. GDF15's intricate modulation within adipose tissue dynamics in response to dietary changes and obesity, coupled with its influence on insulin sensitivity, highlights its critical role in metabolic health. The manuscript delves into the intricate crosstalk between GDF15 and pathways related to insulin sensitivity, macrophage polarization, and adipose tissue function, elucidating its potential as a therapeutic target for metabolic disorders associated with obesity. GDF15's association with chronic low-grade inflammation and its impact on cardiovascular health, particularly during hyperlipidemia and ischemic events, are explored. The intricate relationship between GDF15 and cardiovascular diseases, including its effects on endothelial function, cardiac hypertrophy, and heart failure, emphasizes its multifaceted nature in maintaining overall cardiovascular well-being. Challenges regarding the therapeutic application of GDF15, such as long-term safety concerns and ongoing clinical investigations, are discussed. Lastly, future research directions exploring GDF15's potential in addressing obesity-related complications and cardiovascular risks are proposed, highlighting its promising role as a therapeutic target in reshaping treatment strategies for obesity and associated health conditions.

5-Methoxy-2-aminoindane Reverses Diet-Induced Obesity and Improves Metabolic Parameters in Mice: A Potential New Class of Antiobesity Therapeutics.

The escalating prevalence of obesity and its related disorders represents a daunting global health challenge. Unfortunately, current pharmacological interventions for obesity remain limited and are often associated with debilitating side effects. Against this backdrop, the psychoactive aminoindane derivative 5-methoxy-2-aminoindane (MEAI) has gained considerable attention for its ability to induce a pleasurable, alcohol-like sensation while curbing alcohol consumption. Given the potential impact of MEAI on food addiction and energy homeostasis, we examined its metabolic efficacy on appetite regulation, obesity, and related comorbidities under acute and chronic settings, utilizing a mouse model of diet-induced obesity (DIO). Our results demonstrated that MEAI treatment significantly reduced DIO-induced overweight and adiposity by preserving lean mass and decreasing fat mass. Additionally, MEAI treatment exhibited positive effects on glycemic control by attenuating DIO-induced hyperglycemia, glucose intolerance, and hyperinsulinemia. Furthermore, MEAI reduced DIO-induced hepatic steatosis by decreasing hepatic lipid accumulation and lowering liver triglyceride and cholesterol levels, primarily by inhibiting de novo lipid synthesis. Metabolic phenotyping revealed that MEAI increased energy expenditure and fat utilization while maintaining food consumption similar to that of the vehicle-treated group. Lastly, MEAI normalized voluntary locomotion actions without any overstimulatory effects. These findings provide compelling evidence for the antiobesity effects of MEAI treatment and call for further preclinical testing. In conclusion, our study highlights the potential of MEAI as a novel therapeutic approach for treating obesity and its associated metabolic disorders, offering hope for the development of new treatment options for this global health challenge.

Highly Selective Drug-Derived Fluorescent Probes for the Cannabinoid Receptor Type 1 (CB1R).

The cannabinoid receptor type 1 (CB1R) is pivotal within the endocannabinoid system regulating various signaling cascades with effects in appetite regulation, pain perception, memory formation, and thermoregulation. Still, understanding of CB1R's cellular signaling, distribution, and expression dynamics is very fragmentary. Real-time visualization of CB1R is crucial for addressing these questions. Selective drug-like CB1R ligands with a defined pharmacological profile were investigated for the construction of CB1R fluorescent probes using a reverse design-approach. A modular design concept with a diethyl glycine-based building block as the centerpiece allowed for the straightforward synthesis of novel probe candidates. Validated by computational docking studies, radioligand binding, and cAMP assay, this systematic approach allowed for the identification of novel pyrrole-based CB1R fluorescent probes. Application in fluorescence-based target-engagement studies and live cell imaging exemplify the great versatility of the tailored CB1R probes for investigating CB1R localization, trafficking, pharmacology, and its pathological implications.

Brain Perception of Different Oils on Appetite Regulation: An Anorectic Gene Expression Pattern in the Hypothalamus Dependent on the Vagus Nerve.

(1) Background: We examined the effect of the acute administration of olive oil (EVOO), linseed oil (GLO), soybean oil (SO), and palm oil (PO) on gastric motility and appetite in rats. (2) Methods: We assessed food intake, gastric retention (GR), and gene expression in all groups. (3) Results: Both EVOO and GLO were found to enhance the rate of stomach retention, leading to a decrease in hunger. On the other hand, the reduction in food intake caused by SO was accompanied by delayed effects on stomach retention. PO caused an alteration in the mRNA expression of NPY, POMC, and CART. Although PO increased stomach retention after 180 min, it did not affect food intake. It was subsequently verified that the absence of an autonomic reaction did not nullify the influence of EVOO in reducing food consumption. Moreover, in the absence of parasympathetic responses, animals that received PO exhibited a significant decrease in food consumption, probably mediated by lower NPY expression. (4) Conclusions: This study discovered that different oils induce various effects on parameters related to food consumption. Specifically, EVOO reduces food consumption primarily through its impact on the gastrointestinal tract, making it a recommended adjunct for weight loss. Conversely, the intake of PO limits food consumption in the absence of an autonomic reaction, but it is not advised due to its contribution to the development of cardiometabolic disorders.

Post-COVID-19 Changes in Appetite-An Exploratory Study.

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