Appetite Control Research Articles

Molecular mechanisms of appetite control via 5-HT1B receptors

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Influence of fat-free mass and resting metabolic rate on increased food reinforcement after exercise training

PurposeModels of appetite control have been largely based on negative feedback from gut and adipose signaling to central appetite centers. However, contemporary models posit that fat-free mass (FFM) or the energy demand of FFM [i.e., resting metabolic rate (RMR)] may play a primary role in the motivational drive for food intake (i.e., food reinforcement). The relative reinforcing value of food (RRVfood) is associated with energy intake (EI) and increases with an acute energy deficit. Chronic exercise-induced energy deficits lead to alterations in fat mass (FM), FFM, and RMR and provide an opportunity to test whether change in (∆) FM, ∆FFM, ∆usual EI, or ∆RMR are associated with ∆RRVfood.MethodsParticipants (n = 29, BMI = 25–35 kg/m2) engaged in aerobic exercise expending 300 or 600 kcal, 5 days/weeks for 12 weeks. The reinforcing value of food (PMaxfood) was measured via a computer-based operant responding task and RRVfood was calculated as the reinforcing value of food relative to non-eating sedentary behaviors. RMR was determined by indirect calorimetry and body composition by DXA.ResultsPost-training FFM correlated with usual post-training EI (rs = 0.41, p < 0.05), PMaxfood (rs=0.52, p < 0.01), and RMR (rs = 0.85, p < 0.0001). ∆RMR negatively correlated with ∆PMaxfood (rs = − 0.38, p < 0.05) and with ∆RRVfood (rs = − 0.37, p < 0.05). ∆PMaxfood and ∆RRVfood were not associated with ∆FFM (p = 0.71, p = 0.57, respectively).ConclusionsReductions in RMR with weight loss may increase food reinforcement as means of restoring FFM and RMR to pre-weight loss amounts. Limiting reductions in RMR during weight loss may benefit weight maintenance by restricting increases in food reinforcement after weight loss.

Natural plant fibers obtained from agricultural residue used as an ingredient in food matrixes or packaging materials: A review.

Every year, agrifood activities generate a large amount of plant byproducts, which have a low economical value. However, the valorization of these byproducts can contribute to increasing the intake of dietary fibers and reducing the environmental pollution. This review presents an overview of a wide variety of agricultural wastes applied in the formulation of different food products and sustainable packaging. In general, the incorporation of fibers into bakery, meat, and dairy products was successful, especially at a level of 10% or less. Fibers from a variety of crops improved the consistency, texture, and stability of sauce formulations without affecting sensory quality. In addition, fiber fortification (0.01-6.4%) presented considerable advantages in terms of rheology, texture, melting behavior, and fat replacement of ice cream, but in some cases had a negative impact on color and mouthfeel. In the case of beverages, promising effects on texture, viscosity, stability, and appetite control were obtained by the addition of soluble dietary fibers from grains and fruits with small particle size. Biocomposites used in packaging benefited from reinforcing effects of various plant fiber sources, but the extent of modification depended on the matrix type, fiber pretreatment, and concentration. The information synthesized in this contribution can be used as a tool to screen and select the most promising fiber source, fiber concentration, and pretreatment for specific food applications and sustainable packaging.

Effects of sonication on fatty acid chain length and emulsion stability in curry gravy: A potential approach for satiation perception enhancement

The present study aimed to evaluate the varied sonication amplitudes (60–100%) on the physicochemical properties of medium-chain triglyceride (MCT)-based and long-chain triglyceride (LCT)-based in curry gravy. This work also aimed to determine the effects of the sonicated curry gravy at optimum amplitude and in-vitro lipid digestibility as the potential indication of satiation perception. Curry gravy was chosen as food model in this study as it is one of the most preferred meals in South-East Asia countries. The application of sonication treatment significantly reduced (p < 0.05) the droplet size of MCT-based curry gravy from 119 μm to the smallest 29 μm (sonicated at 80%) and LCT-based curry gravy from 132.5 μm to the smallest 29 μm (sonicated at 70%). Sonication treatment increased the lightness of MCT-based and LCT-based curry gravy from 33.67 to 52.10 and 33.50 to 50.50, respectively. The increase of sonication amplitudes increased the consistent flow index of MCT-based (from 0.05 to range 0.24–0.60) and LCT-based curry (from 0.05 to range 0.20–0.27). All sonicated samples exhibited shear-thinning behaviour. The rate of fatty acid released during in vitro lipid digestibility increased by at least 30% for both MCT-based and LCT-based curry gravy after sonication at 80% amplitude. Results obtained indicate effectiveness of sonication in potentially prolonging satiation perception by producing small fat globule droplets size, more even and stable emulsion with greater viscosity independent of the fatty acid chain length (MCT or LCT). It provides useful information in developing food emulsion system with enhanced satiating power predominantly in appetite control.

Acute and short-term effects of Lactobacillus paracasei subsp. paracasei 431 and inulin intake on appetite control and dietary intake: A two-phases randomized, double blind, placebo-controlled study

This study aims to examine the acute and short-term effects of prebiotics, probiotics, and their combination on appetite, energy intake and satiety related hormones in two phases. The first phase was a randomized, double blind, placebo controlled crossover study. Prebiotic (16 g inulin), probiotic (Lactobacillus paracasei subsp. paracasei 431 (L. casei 431) (>106 cfu/ml), synbiotic (their combination) and control (16 g maltodextrin) dairy drinks were consumed by 16 healthy men with a standard breakfast on four separate test days, and the following satiety responses and ad libitum food intake at lunch and over 24 h were assessed. In the second phase, the effects of 21 days of synbiotic (n = 10) or control (n = 11) drink consumption on appetite sensation, energy intake, serum glucose, insulin, peptide YY, ghrelin, obestatin and adiponectin concentration were assessed in a randomized double-blind placebo-controlled design. In the first phase, energy intake values during ad libitum lunch were the lowest in the prebiotic drink, followed by probiotic, synbiotic and control drinks, respectively (p = 0.017); also the rest of the day and 24-h dietary energy intake was lower by prebiotic and probiotic drinks compared to the control drink (p < 0.05 for each). For short-term effects, no significant difference in anthropometric measurements, hunger-satiety scores and serum glucose, insulin, PYY, ghrelin, obestatin and adiponectin concentrations were recorded. Despite the potential of prebiotics and probiotics to reduce energy intake, further studies are required for a better understanding of their role in satiety related mechanisms.

Pellets Inoculated with Bacillus amyloliquefaciens H57 Modulates Diet Preference and Rumen Factors Associated with Appetite Regulation in Steers

Simple SummaryThe probiotic Bacillus amyloliquefaciens strain H57 (H57) may reinforce preferential feeding behaviour by changing ruminal fermentation parameters. Four rumen-fistulated steers were offered feedlot pellets, with (H57) or without (Control, C) the H57 probiotic. Half of the pellets were added to the rumen, at time zero, and half were offered for oral consumption over the next six hours, to make four feeding treatments. Each steer was offered each treatment over time. Each offering was over six days, with rumen fluid sampled over the last three days for a six-hour period per day. A five-minute preference test was performed at the end of each rumen sampling period by simultaneously offering the steers 4 kg of H57 and C pellets. The steers preferred the H57 over the C pellets but the route of offering (rumen versus oral) had no effect on preference. Ruminal pH and molar proportions of iso-butyrate and iso-valerate were higher and ammonia concentrations tended to be greater for H57 compared to C. However, since the route of offering had no effect on preference, the hypothesis, that ruminal fermentation changes take precedence over oral (taste) sensations in driving preference, was not supported.This study examined whether the probiotic Bacillus amyloliquefaciens strain H57 (H57) affects ruminal fermentation parameters that exercise post-ingestive feedback appetite control mechanisms. A 4 × 4 Latin square design was used to separate pre- and post-ingestive effects of H57 in four rumen-fistulated steers. The steers were offered a set amount of feedlot pellets, inoculated with H57 or without H57 (control, C). Half of the total amount of pellets fed were introduced intra-ruminally (r), and then the remaining pellets were orally consumed (o) to make four feeding treatments: H57r/H57o, H57r/Co, Cr/H57o and Cr/Co. Rumen fluid was sampled at 2, 4 and 6 h after feeding. Preference behaviour was tested immediately after the 6 h rumen fluid sampling by simultaneously offering the steers 4 kg of each of H57 and C pellets in adjacent troughs for 5 min. Steers preferred the pellets with added H57 over the C pellets (56:44; p < 0.001) and their preferences were not affected by the treatment protocol imposed to separate post- from pre-ingestive effects (p > 0.05). Steers fed H57 pellets had higher ruminal pH, molar proportions of iso-butyrate and iso-valerate (p < 0.05) and tended to have greater ruminal ammonia concentrations compared to those fed C pellets (p < 0.1). However, post-ingestive signals did not affect diet preference more than pre-ingestive signals.

Metabolic profiles, energy expenditures, and body compositions of the weight regain versus sustained weight loss patients who underwent Roux-en-Y gastric bypass.

Weight regain (WR) has been an emerging problem after Roux-en Y gastric bypass (RYGB) and little is known about the mechanisms of WR after RYGB. To evaluate the mechanisms of WR after RYGB through the postprandial gut hormones response, particularly glucagon-like peptide-1 (GLP-1), which regulates appetite control, energy expenditure, body composition, physical activities, dietary intake, and psychological factors. Duke University Medical Center, Durham, North Carolina. A cross sectional study of 34 patients who underwent RYGB at least 2 years and achieved ≥50% of excess weight loss at 1year was conducted. The subjects were categorized into WR group or sustained weight loss group, based upon whether their WR was ≥15% of postoperative lowest weight. The WR group had less augmented postprandial GLP-1 response but exaggerated hyperinsulinemia. Postprandial peptide YY, ghrelin, and glucose were not different between group. Patients who regained weight required less weight-adjusted energy expenditure and had more percentage body fat and less percentage lean mass. The caloric intake and diet composition were comparable between groups; however, the WR group had higher depression scores, binge eating scales, and hunger rating and spent significantly less time on vigorous exercise. The mechanisms of WR in patients who were initially successful after RYGB are complex and involved not only the role of postprandial gut hormone response but are also related to energy expenditure adaptation and body composition changes. Moreover, food preference and physical activity may play roles in weight control after bariatric surgery. Further prospective controlled trial is needed to explore the mechanisms of WR.

CNS GNPDA2 Does Not Control Appetite, but Regulates Glucose Homeostasis.

GNPDA2 has been associated with human obesity and type-2 diabetes by using a GWAS approach. GNPDA2 is an enzyme involved in the hexosamine biosynthesis pathway, which is known to be important for nutrient sensing in various organism. Its counter enzyme, GFAT, has previously been shown to be important to the development of insulin resistance in diabetes. The implication of GNPDA2 and GFAT in metabolism is scarce and the effect of both enzymes over appetite and glucose homeostasis is unknown.Aim: Identify the role of GNPDA2 and GFAT in nutrient sensing circuits of the CNS that are important for the regulation of both appetite and glucose homeostasis.Methods: Using Long Evans rats, we administered either a GNPDA2 or GFAT antagonist or vehicle in i3vt.Key Findings: GNPDA2 is highly expressed in hypothalamus and adipose tissue, followed by muscle and liver. GNPDA2 is expressed in different hypothalamic nuclei (ARC, DMH, LHA, PVN). GNPDA2 is downregulated in hypothalamus under diet-induced obesity (as previously described), but GFAT expression does not change. Moreover, i3vt infusion of GNPDA2 or GFAT inhibitor resulted in increased c-Fos in areas related to appetite and glucose homeostasis control as PVN and DMH and to a lesser extent in the LHA and ARC. Central inhibition of GNPDA2 does not alter either acute food intake or body weight; however, GFAT inhibition diminished appetite and body weight due to visceral illness. In addition, central administration of the GNPDA2 antagonist, prior to an intraperitoneal glucose tolerance test, resulted in glucose intolerance in comparison to vehicle without altering insulin levels.Significance: These results suggest that central GNPDA2 does not control appetite, but regulates glucose homeostasis.

Probiotics for Mental Health: A Review of Recent Clinical Trials.

The digestive system is involved in providing both regulatory and biochemical signaling to the nervous system via the gut-brain axis. Major brain neurotransmitters within the enteric nervous system include acetylcholine, serotonin, and norepinephrine, which are triggered by various stimuli within the digestive system, including the microbiota. Associations between the gut microbiome and activation of neuroreceptors and neurotransmitters are related to factors such as appetite control, mood, and memory. This column presents the results of a brief review of recently published clinical trials related to gut microbiome interventions (n = 11) that aimed to address a variety of mental health outcomes. The impacts of probiotics on mental health and other clinical outcomes vary by the health of study participants. Continuing research on the mental health benefits of probiotics in healthy individuals is necessary.

Serum Neudesin Levels in Obese Adolescents

Objective:Advances in knowledge of neurotrophic factors are now revealing the complex control of energy homeostasis and appetite, as well as the crucial role these factors play in nervous system function. The aim of this study was to assess serum levels of neudesin in adolescents with obesity and to examine the relationship between these levels and metabolic outcomes.Methods:Adolescents, aged 10-17 years were enrolled. Subjects were divided into normal weight, obese and morbidly obese subgroups. Serum neudesin concentrations were compared between the groups.Results:In total, 88 adolescents were recruited, of whom 30 (34.1%) were normal weight, 15 (17.0%) were obese and 43 (48.9%) were morbidly obese. Neudesin levels were significantly lower in obese adolescents than in the control group (p=0.013). A correlation analysis applied to the whole study group revealed a negative correlation between serum neudesin concentration and body mass index (BMI) z scores (r=-0.40, p<0.001). Serum neudesin levels tended to increase in adolescents with metabolic syndrome, insulin resistance, dyslipidaemia, and hypertension but the differences were not significant (p=0.259, p=0.246, p=0.259, and p=0.523, respectively).Conclusion:Serum neudesin levels were significantly correlated with BMI z score in obese adolescents. Generally, serum neudesin levels were low in obese and morbidly obese adolescents and tended to increase with the appearance of metabolic disorders. Both obesity and associated metabolic disorders have multifactorial causes. Therefore, we suggest that the role of the neudesin molecule in the regulatory mechanisms of obesity and metabolic disorders should be further investigated with well-designed studies enrolling larger groups.

Signal Transduction of Mineralocorticoid and Angiotensin II Receptors in the Central Control of Sodium Appetite: A Narrative Review.

Sodium appetite is an innate behavior occurring in response to sodium depletion that induces homeostatic responses such as the secretion of the mineralocorticoid hormone aldosterone from the zona glomerulosa of the adrenal cortex and the stimulation of the peptide hormone angiotensin II (ANG II). The synergistic action of these hormones signals to the brain the sodium appetite that represents the increased palatability for salt intake. This narrative review summarizes the main data dealing with the role of mineralocorticoid and ANG II receptors in the central control of sodium appetite. Appropriate keywords and MeSH terms were identified and searched in PubMed. References to original articles and reviews were examined, selected, and discussed. Several brain areas control sodium appetite, including the nucleus of the solitary tract, which contains aldosterone-sensitive HSD2 neurons, and the organum vasculosum lamina terminalis (OVLT) that contains ANG II-sensitive neurons. Furthermore, sodium appetite is under the control of signaling proteins such as mitogen-activated protein kinase (MAPK) and inositol 1,4,5-thriphosphate (IP3). ANG II stimulates salt intake via MAPK, while combined ANG II and aldosterone action induce sodium intake via the IP3 signaling pathway. Finally, aldosterone and ANG II stimulate OVLT neurons and suppress oxytocin secretion inhibiting the neuronal activity of the paraventricular nucleus, thus disinhibiting the OVLT activity to aldosterone and ANG II stimulation.

The role of cholecystokinin and peptide YY in feed intake in Atlantic halibut (Hippoglossus hippoglossus) larvae

Control of appetite and feed intake in fish larvae are still largely unexplored. Two of the key players in controlling vertebrate's feed intake are cholecystokinin (CCK) and peptide YY (PYY). Here we investigated the mRNA expression of pyy, cck and cck receptors (cckr) in the brain (head) and gut of Atlantic halibut larvae in response to three consecutive meals. We used Artemia nauplii cysts that are commonly ingested by halibut larvae when present as inert feed, and three water-soluble extracts as attractants to stimulate appetite. Cyst intake was not affected by the use of attractants and overall ingestion rate was low. Differences in mRNA expression of cck and pyy were observed between the halibut larvae that had eaten and those that had not despite readily available feed (cysts), supporting that mechanisms for control of feed intake are at least partly functional. All genes analysed were present in the brain and gut, however the different expression profiles between paralogues suggest potential divergent functions. In the gut, cck2 and pyyb mRNA expression was significantly higher in the larvae that ate cysts compared to larvae that decided to not eat, indicating that these genes play a satiety function in the halibut larvae similar to the general vertebrate scheme. However, cck2, cck2r1, and pyy mRNA expression in the brain were lower in the fed-filled larvae group compared to larvae before eating, which contrasts with the presumable anorectic function of these genes. Further research is required to fully evaluate how PYY and CCK affect the feeding biology in halibut larvae, contributing to formulate inert diets that can stimulate appetite and feed intake.

Gastrointestinal Hormones in Healthy Adults: Reliability of Repeated Assessments and Interrelations with Eating Habits and Physical Activity.

Background: Gastrointestinal hormones (GIHs) are crucial for the regulation of a variety of physiological functions and have been linked to hunger, satiety, and appetite control. Thus, they might constitute meaningful biomarkers in longitudinal and interventional studies on eating behavior and body weight control. However, little is known about the physiological levels of GIHs, their intra-individual stability over time, and their interaction with other metabolic and lifestyle-related parameters. Therefore, the aim of this pilot study is to investigate the intra-individual stability of GIHs in normal-weight adults over time. Methods: Plasma concentrations of ghrelin, leptin, GLP-1 (glucagon-like-peptide), and PP (pancreatic polypeptide) were assessed by enzyme-linked immunosorbent assay (ELISA) in 17 normal-weight, healthy adults in a longitudinal design at baseline and at follow-up six months later. The reliability of the measurements was estimated using intra-class correlation (ICC). In a second step, we considered the stability of GIH levels after controlling for changes in blood glucose and hemoglobin A1 (HbA1c) as well as self-reported physical activity and dietary habits. Results: We found excellent reliability for ghrelin, good reliability for GLP1 and PP, and moderate reliability for leptin. After considering glucose, HbA1c, physical activity, and dietary habits as co-variates, the reliability of ghrelin, GLP1, and PP did not change significantly; the reliability of leptin changed to poor reliability. Conclusions: The GIHs ghrelin, GLP1, and PP demonstrated good to excellent test–retest reliability in healthy individuals, a finding that was not modified after adjusting for glucose control, physical activity, or dietary habits. Leptin showed only moderate to poor reliability, which might be linked to weight fluctuations, albeit small, between baseline and follow-up assessment in our study sample. Together, these findings support that ghrelin, GLP1, and PP might be further examined as biomarkers in studies on weight control, with GLP1 and PP serving as anorexic markers and ghrelin as an orexigenic marker. Additional reliability studies in obese individuals are necessary to verify or refute our findings for this cohort.

Brain Distribution of 10 cart Transcripts and Their Response to 4 Days of Fasting in Atlantic Salmon (Salmo salar L.)

Cocaine- and amphetamine-regulated transcript (CART) has been known to be involved in feeding and energy balance in mammals, acting as an anorexigenic neuropeptide in hypothalamus. In Atlantic salmon, little is known about Cart brain localization and its function. In this study, in silico analysis revealed the existence of 10 cart paralogs, here named cart1a, 1b1, 1b2, 2a, 2b1, 2b2, 3a1, 3a2, 3b, and 4. The Atlantic salmon Cart sequences shared from 19 to 50% of identity with the human homolog and between 25 and 90% of sequence identity among paralogs, except for Cart4 which only shared 18–23% of identity. We further explored cart mRNA expressions in 8 brain regions (Olfactory Bulb-OB, Telencephalon-TEL, Midbrain-MB, Cerebellum-CE, Hypothalamus-HYP, Saccus vasculosus-SV, Pituitary-PT, and Brain Stem-BS) of Atlantic salmon smolt under 4 days of fasting and continuous fed conditions. The cart paralogs analyzed were widely distributed among the brain regions and OB, TEL, HYP, MB, and BS seemed to be the major sites of expression. The expression of cart1a and 1b showed quite similar pattern in MB, HYP, and BS. The expression of cart2a had the highest in MB followed by HYP and TEL. The cart3a transcript was widely distributed in rostrocaudal regions of brain except in OB and SV whereas cart3b was predominantly expressed in BS followed by MB. Expression of cart4 was high in HYP followed by TEL. With regards to effect of feeding status the Atlantic salmon cart2b, which is the most abundant among the paralogs, was upregulated after 4 days of fasting in OB, MB, and HYP compared to fed group. This may suggest an unexpected, but possible orexigenic role of cart2b in Atlantic salmon or a fasting induced stress effect. No other significant effect was observed. Collectively, the differential expressions of the cart paralogs in different brain regions suggest that they may have roles in regional integration of appetite signals and are possibly involved in regulating other brain functions in Atlantic salmon. The fact that salmon has 10 cart paralogs, while mammalians only one, opens interesting perspectives for comparative research on evolutionary adaptations of gene function in the control of appetite and energy homeostasis.

Experimental studies and randomised controlled trial investigating the impact of traditional dried fruits consumed as snacks on food intake, experience of appetite and bodyweight

AbstractTwo studies investigating the impact of dried fruits eaten as a snack on weight control were designed to examine the effects of prunes and raisins on appetite (phase 1), and whether prunes undermine weight loss, due to the increase in energy density on drying, when included in a structured weight loss programme (phase 2). Phase 1 compared the effect on appetite of equi‐weight or equi‐caloric snacks of prunes (100 or 140 g) and raisins (100 or 111 g) with a control condition (100 g/335 kcal jelly babies), in a pre‐load, cross‐over design (n = 40 analysed). A significant effect of condition on food intake was observed, with significantly lower weight of food consumed in the 140 g prune group versus control, and on Area Under the Curve (AUC) fullness, due to a greater effect in the 140 g prune group versus control. In phase 2, change in bodyweight and waist circumference were measured in a 12‐week randomised, parallel‐groups intervention study (n = 100 analysed, 50 per group). Prunes (females: 140 g, males: 171 g/day) replaced usual snacks whilst following a weight loss programme. The active control group followed the same programme and participants were instructed on healthy snacking. A significant reduction in mean bodyweight in the prune group versus baseline was consistent with the phase 1 evidence that prunes can aid appetite control, although it could also be explained by overall diet in the context of a structured weight loss programme. Prunes did not produce a detrimental effect on mean weight loss over 12 weeks versus control (prune group: −1.99 kg; active control: −1.53 kg), nor on decrease in waist circumference (prune group: −2.40 cm; active control: −1.74 cm). No additional benefit on weight loss was seen (between‐group difference was non‐significant). The daily intake of prunes was well‐tolerated. Phase 1 demonstrated that prune snacks produced beneficial changes in appetite. Phase 2 demonstrated that prunes did not undermine weight management, and this warrants further study.

The Peripheral Cannabinoid Receptor Type 1 (CB1) as a Molecular Target for Modulating Body Weight in Man.

The cannabinoid 1 (CB1) receptor regulates appetite and body weight; however, unwanted central side effects of both agonists (in wasting disorders) or antagonists (in obesity and diabetes) have limited their therapeutic utility. At the peripheral level, CB1 receptor activation impacts the energy balance of mammals in a number of different ways: inhibiting satiety and emesis, increasing food intake, altering adipokine and satiety hormone levels, altering taste sensation, decreasing lipolysis (fat break down), and increasing lipogenesis (fat generation). The CB1 receptor also plays an important role in the gut–brain axis control of appetite and satiety. The combined effect of peripheral CB1 activation is to promote appetite, energy storage, and energy preservation (and the opposite is true for CB1 antagonists). Therefore, the next generation of CB1 receptor medicines (agonists and antagonists, and indirect modulators of the endocannabinoid system) have been peripherally restricted to mitigate these issues, and some of these are already in clinical stage development. These compounds also have demonstrated potential in other conditions such as alcoholic steatohepatitis and diabetic nephropathy (peripherally restricted CB1 antagonists) and pain conditions (peripherally restricted CB1 agonists and FAAH inhibitors). This review will discuss the mechanisms by which peripheral CB1 receptors regulate body weight, and the therapeutic utility of peripherally restricted drugs in the management of body weight and beyond.

The feeding behaviour of Amyotrophic Lateral Sclerosis mouse models is modulated by the Ca2+ -activated KCa 3.1 channels.

Background and PurposeAmyotrophic lateral sclerosis (ALS) patients exhibit dysfunctional energy metabolism and weight loss, which is negatively correlated with survival, together with neuroinflammation. However, the possible contribution of neuroinflammation to deregulations of feeding behaviour in ALS has not been studied in detail. We here investigated if microglial KCa3.1 is linked to hypothalamic neuroinflammation and affects feeding behaviours in ALS mouse models.Experimental ApproachhSOD1G93A and TDP43A315T mice were treated daily with 120 mg·kg−1 of TRAM‐34 or vehicle by intraperitoneal injection from the presymptomatic until the disease onset phase. Body weight and food intake were measured weekly. The later by weighing food provided minus that left in the cage. RT‐PCR and immunofluorescence analysis were used to characterize microglia phenotype and the main populations of melanocortin neurons in the hypothalamus of hSOD1G93A and age‐matched non‐tg mice. The cannabinoid–opioid interactions in feeding behaviour of hSOD1G93A mice were studied using an inverse agonist and an antagonist of the cannabinoid receptor CB1 (rimonabant) and μ‐opioid receptors (naloxone), respectively.Key ResultsWe found that treatment of hSOD1G93A mice with the KCa3.1 inhibitor TRAM‐34 (i), attenuates the pro‐inflammatory phenotype of hypothalamic microglia, (ii) increases food intake and promotes weight gain, (iii) increases the number of healthy pro‐opiomelanocortin (POMC) neurons and (iv), changes the expression of cannabinoid receptors involved in energy homeostasis.Conclusion and ImplicationsUsing ALS mouse models, we describe defects in the hypothalamic melanocortin system that affect appetite control. These results reveal a new regulatory role for KCa3.1 to counteract weight loss in ALS.

Serum Leptin Level in Children with Acute Lymphoblastic Leukemia

Abstract Background Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer .It is a disease of monoclonal proliferation of hematopoietic precursor cells of the lymphoid series within the bone marrow. Leptin is a peptide hormone which is predominantly produced by white adipose tissue. The main function of leptin in the human body is the regulation of energy expenditure and control of appetite .It is supposed to be involved in the pathogenesis of hematological malignancy through its proliferative, anti-apoptotic, and differentiating effects on hematopoietic neoplastic cells, in addition to its synergestic effect on vascular endothelial growth factor (VGEF) . Objectives To evaluate serum leptin level in children with acute lymphoblastic leukemia at diagnosis and at day 28 post induction chemotherapy,and to test the association between serum leptin levels and anthropometric measures of ALL patients and prognostic markers of ALL as age, gender, initial WBCS count, extramedullary infiltration to organs and CSF, cytogenetics, and response to treatment . Patients and Methods This is a case- control study performed at Clinical Pathology Department, Ain Shams University Hospitals. The study was conducted on 30 ALL pediatric patients admitted to Hematology &amp; Oncology Unit, Pediatric Department, Ain Shams University Hospitals.The patients were evaluated at diagnosis before intake of chemotherapy and at day 28 post-induction chemotherapy, and 25 healthy controls matched with patients in age, sex, BMI. Results Serum leptin level is elevated in ALL patients at diagnosis as compared to controls .It has no significant relation with patients age, sex, BMI. It is elevated in patients who received cranial radiotherapy and those who relapsed. .However, it has no significant relation with clinical data (fever, lymphadenopathy and organomegaly) and laboratory characteristics (CBC, percentage of blasts infiltrating bone marrow and peripheral blood, immunophenotyping and cytogenetics) of ALL patients. Conclusion Data from our study showed that elevated leptin level in ALL patients can be considered a risk factor involved in ALL pathogenesis.It can be used as a biomarker for ALL diagnosis, a prognostic factor for ALL patients on chemotherapy, and a predicting factor for relapse.

Trefoil Factor Family Member 2 Expression as an Indicator of the Severity of the High-Fat Diet-Induced Obesity.

Trefoil Factor Family Member 2 (TFF2) belongs to TFF family peptides that includes TFF1, TFF2, TFF3. TFF2 is mainly known for its roles in the mucosal protection. In the context of obesity and high fat diet (HFD), Tff2 has been characterized as a HFD-induced gene. The knock-out of Tff2 in mice lead to the protection from HFD-induced obesity with a metabolic profile towards a negative energy balance. Such HFD-specific expression gives Tff2 a pattern worth exploring in biomedical research. Indeed, measuring TFF2/TFF2/Tff2 expression in biological samples following the ingestion of high-fat diet reflects the biological “responsiveness” to the lipids ingestion and would reflect the severity of obesity establishment afterwards. Such property could be explored for instance to screen animal models, evaluate the predisposition to HFD-induced obesity as well as in biomedical and clinical applications. Results might advance obesity research especially in terms of understanding lipid-induced signals, appetite control and adiposity storage.

CYP1A2 polymorphisms modify the association of habitual coffee consumption with appetite, macronutrient intake, and body mass index: results from an observational cohort and a cross-over randomized study.

Evidence regarding the influence of coffee on appetite and weight control is equivocal and the influence of covariates, such as genetic variation in caffeine metabolism, remains unknown. Herein, we addressed the novel hypothesis that genetic variation in CYP1A2, a gene responsible for more than 95% of caffeine metabolism, differentially impacts the association of coffee consumption with appetite and BMI among individuals with different genetic predispositions to obesity. A cross-over randomized intervention study involving 18 volunteers assessed the effects of coffee consumption on dietary intake, appetite, and levels of the appetite-controlling hormones asprosin and leptin. Data on habitual coffee intake, BMI, and perceived appetite were obtained from an observational cohort of 284 volunteers using validated questionnaires. Participants were stratified according to a validated genetic risk score (GRS) for obesity and to the -163C > A (rs762551) polymorphism of CYP1A2 as rapid (AA), intermediate (AC), or slow (CC) caffeine metabolizers. Coffee consumption led to lower energy and dietary fat intake and circulating asprosin levels (P for interaction of rs762551 genotype*coffee consumption=0.056, 0.039, and 0.043, respectively) as compared to slow/intermediate metabolizers. High coffee consumption was more prevalent in rapid compared to slow metabolizers (P = 0.008 after adjustment for age, sex, and BMI) and was associated with lower appetite perception and lower BMI only in rapid metabolizers (P for interaction of rs762551 genotype*coffee consumption = 0.002 and 0.048, respectively). This differential association of rs762551 genotype and coffee consumption with BMI was more evident in individuals at higher genetic risk of obesity (mean adjusted difference in BMI = -5.82 kg/m2 for rapid versus slow/intermediate metabolizers who consumed more than 14 cups of coffee per week). CYP1A2 rs762551 polymorphism modifies the association of habitual coffee consumption with BMI, in part by influencing appetite, energy intake and circulating levels of the orexigenic hormone asprosin. This association is more evident in subjects with high genetic predisposition to obesity. ClinicalTrials.gov: registered Clinical Trial NCT04514588.