Feeding Center Research Articles

Targeting the divergent TGFβ superfamily cytokine MIC-1/GDF15 for therapy of anorexia/cachexia syndromes.

To review recent finding on MIC-1/GDF15 and re-evaluate it as a potential target for the therapy of anorexia/cachexia syndromes. MIC-1/GDF15 consistently induces anorexia/cachexia in animal models. Its actions on brainstem feeding centers leads to anorexia, inducing prolonged undernutrition and consequent loss of both lean and fat mass. Epidemiological studies by multiple groups have linked substantially elevated serum levels of this cytokine to anorexia/cachexia syndromes in diverse diseases such as cancer, chronic renal and cardiac failure, and chronic obstructive lung disease. These elevated serum levels are similar to those required to induce this syndrome in animals. Recent identifications of its previously elusive receptor as GFRAL, has enhanced understanding of its biology and suggests that modulating the MIC-1/GDF15-GFRAL pathway may be a therapeutic target for anorexia/cachexia syndrome. Inhibiting MIC-1/GDF15 or its receptor GFRAL are high-value potential targets for treatment of anorexia/cachexia syndrome in patients whose elevated serum levels may justify its use.

Acoustic observations of the vertical distribution and latitudinal range of small pelagic fish schools in the Midriff Islands Region, Gulf of California, Mexico

Within the Gulf of California, the Midriff Islands Region (MIR) is characterized by mixing conditions of water masses that lead to high primary productivity, which fosters the presence of sardines, anchovies, and their predators. Using acoustic tools, we analyzed the presence and characteristics of schools detected in three surveys carried out in late spring of 2012 and 2013 and early summer of 2014. We sought to relate changes in the geographical distribution of schools with Sea Surface Temperature (SST) and Net Primary Productivity (NPP). The largest number of schools was observed in 2012, coinciding with the highest and most extensive NPP, while the following years were associated with lower NPP coupled with a lower number of detections. During the study period, the Ballenas-Salsipuedes Channel and its area of influence showed the lowest SST and higher NPP even toward the summer as compared to the rest of the MIR, favoring the presence of fish schools and supporting the importance of this site as a feeding center for these species. As for their vertical distribution, it was found that during the day schools reach greater depths, while during the night these are concentrated in surface waters. However, no differences in size, density, or other characteristics were detected either between periods or between years. Finally, we found a high proportion of schools during the night (61%), which departs from the typical nocturnal dispersal behavior described for similar species in other areas.

Breast Feeding Centre WA: identifying the need for increased support for mothers of early term and late preterm infants with breast feeding challenges following discharge

Breast Feeding Centre WA: identifying the need for increased support for mothers of early term and late preterm infants with breast feeding challenges following discharge

LEAN Management of an Infant Feeding Center Improves Patient Safety and Decreases Costs

Improve processes for infant feeding in hospitals to improve patient safety and decrease costs.

Pengaruh integrasi intervensi gizi dan stimulasi tumbuh kembang terhadap peningkatan berat badan dan perkembangan balita kurus

Background: Indonesia has faced the problem where double burden malnutrition increasing. On the other hand, malnutrition in children may affect the development both in early childhood and the quality of human capital in later life.Objective: This study aimed to examine the effect of integration of nutrition intervention and development stimulation on weight gain and development of wasted children.Method: Design used in this study was quasi-experimental with pre- and post-test control group. Subjects were 38 children under-five resided in Sedayu Subdistrict. Sampels were selected by using total sampling of children under-five in community feeding center, meanwhile controls were children under-five selected from integrated health posts in another villages with the ratio of 1:1. Interventions given were education, development stimulation and food supplementation package distributed by the community health workers whom were given capacity building. Analysis used were Mann-Whitney U and Wilcoxon Signed Rank tests at the level of significance 0,05.Results: Children in intervention groups gained their weight significantly from before (9.17±1.89) and after (9.27±1.79) intervention (p=0.04). Meanwhile, development impairment score decreased from 1.32±0.75 to 0.42±0.61 significantly (p=0.00).Conclusion: Intervention package containing nutrition and development education, development stimulation and supplementary food through community feeding center (CFC) sucessfully increased body weight and development of wasted children significantly.

Transcriptome analysis of tetrodotoxin sensing and tetrodotoxin action in the central nervous system of tiger puffer <i>Takifugu rubripes</i> juveniles

To reveal the sensing of tetrodotoxin (TTX) by tiger puffer Takifugu rubripes juveniles and its action in the central nervous system (CNS), we conducted transcriptome analysis using next-generation sequencing for the olfactory system and brain of non-toxic cultured juveniles administered TTX. Sixty-seven million reads from the nasal region (olfactory epithelium and skin) and the brain of each of three individuals of the control, TTX-sensing and TTX-administered juveniles were assembled into 153,958 contigs. Mapping raw reads from each sample onto the nucleotide sequences of predicted transcripts in the T. rubripes genome (FUGU version 4) and the de novo assembled contigs to investigate their frequency of expression revealed that the expression of 21 and 81 known genes significantly changed in TTX-sensing and TTX-administered juveniles in comparison with control juveniles, respectively. These genes included those related to feeding regulation and a reward system, and indicated that TTX ingestion of T. rubripes juveniles is controlled in the feeding center in the brain, that T. rubripes may sense TTX as a reward, and that accumulated TTX directly acts on the central nervous system to adjust TTX ingestion.

New insight into GABAergic neurons in the hypothalamic feeding regulation.

Several lines of study have suggested that GABA in the hypothalamic feeding center plays a role in promoting food intake. Recent studies revealed that not only NPY/AgRP neurons in the hypothalamic arcuate nucleus (ARC) that co-express GABA but also other GABAergic neurons act as an orexigenic. Here, we review the progress of studies on hypothalamic GABAergic neurons distributed in ARC, dorsomedial hypothalamus (DMH), and lateral hypothalamus (LH). Three advanced technologies have been applied and greatly contributed to the recent progress. Optogenetic (and chemogenetic) approaches map input and output pathways of particular subpopulations of GABAergic neurons. In vivo Ca2+ imaging using GRIN lens and GCaMP can correlate the activity of GABAergic neuron subpopulations with feeding behavior. Single-cell RNA-seq approach clarifies precise transcriptional profiles of GABAergic neuron subpopulations. These approaches have shown diversity of GABAergic neurons and the subpopulation-dependent role in feeding regulation.

Change in the Binding of [11C]BU99008 to Imidazoline I2 Receptor Using Brain PET in Zucker Rats.

The imdazoline I2 receptor (I2R) has been found in the feeding centers of the brain, such as the hypothalamus, and certain I2R ligands have been reported to stimulate food intake. Thus, it has been proposed that I2R may play a role in feeding control. [11C]BU99008 was developed as a positron emission tomography (PET) tracer for imaging of I2R. [11C]BU99008 displayed relatively high brain penetration and specific binding by brain PET studies in preclinical studies. Here, we evaluated a pathological condition caused by obesity related to I2R function by quantitative PET study using [11C]BU99008. PET scans were acquired in the Zucker (ZUC) lean and fatty rats, radioactivity and metabolites of plasma were measured, and the kinetic parameters were estimated. Radioactivity levels after the injection of [11C]BU99008 in the hypothalamus of both ZUC lean and fatty rats were highly accumulated, and then gradually decreased until 60min after the injection. The accumulated radioactivity from 30 to 60min after the injection in the hypothalamus of the ZUC fatty rats was 1.3 times greater than that of lean rats. The volume of distribution (VT) estimated by Logan graphical analysis in the hypothalamus of the ZUC fatty rats was 1.8 times greater than that in the ZUC lean rats. In metabolite analysis, the percentages of the unchanged form in the plasma of the ZUC fatty rats at 60min after the injection (5.0%) was significantly lower than that of lean rats (9.1%). By PET imaging using [11C]BU99008, we demonstrated that the accumulated radioactivity and estimated VT value in the feeding center of ZUC lean rats was lower than that in fatty rats. PET studies using [11C]BU99008 may contribute to elucidate a pathological condition caused by obesity related to I2R function.

Hedonic Eating and the "Delicious Circle": From Lipid-Derived Mediators to Brain Dopamine and Back.

Palatable food can be seductive and hedonic eating can become irresistible beyond hunger and negative consequences. This is witnessed by the subtle equilibrium between eating to provide energy intake for homeostatic functions, and reward-induced overeating. In recent years, considerable efforts have been devoted to study neural circuits, and to identify potential factors responsible for the derangement of homeostatic eating toward hedonic eating and addiction-like feeding behavior. Here, we examined recent literature on “old” and “new” players accountable for reward-induced overeating and possible liability to eating addiction. Thus, the role of midbrain dopamine is positioned at the intersection between selected hormonal signals involved in food reward information processing (namely, leptin, ghrelin, and insulin), and lipid-derived neural mediators such as endocannabinoids. The impact of high fat palatable food and dietary lipids on endocannabinoid formation is reviewed in its pathogenetic potential for the derangement of feeding homeostasis. Next, endocannabinoid signaling that regulates synaptic plasticity is discussed as a key mechanism acting both at hypothalamic and mesolimbic circuits, and affecting both dopamine function and interplay between leptin and ghrelin signaling. Outside the canonical hypothalamic feeding circuits involved in energy homeostasis and the notion of “feeding center,” we focused on lateral hypothalamus as neural substrate able to confront food-associated homeostatic information with food salience, motivation to eat, reward-seeking, and development of compulsive eating. Thus, the lateral hypothalamus-ventral tegmental area-nucleus accumbens neural circuitry is reexamined in order to interrogate the functional interplay between ghrelin, dopamine, orexin, and endocannabinoid signaling. We suggested a pivotal role for endocannabinoids in food reward processing within the lateral hypothalamus, and for orexin neurons to integrate endocrine signals with food reinforcement and hedonic eating. In addition, the role played by different stressors in the reinstatement of preference for palatable food and food-seeking behavior is also considered in the light of endocannabinoid production, activation of orexin receptors and disinhibition of dopamine neurons. Finally, type-1 cannabinoid receptor-dependent inhibition of GABA-ergic release and relapse to reward-associated stimuli is linked to ghrelin and orexin signaling in the lateral hypothalamus-ventral tegmental area-nucleus accumbens network to highlight its pathological potential for food addiction-like behavior.

Weaning stage hyperglycemia induces glucose-insensitivity in arcuate POMC neurons and hyperphagia in type 2 diabetic GK rats

Hyperphagia triggers and accelerates diabetes, and prevents proper dietary control of glycemia. Inversely, the impact of hyperglycemia on hyperphagia and possible mechanistic cause common for these two metabolic disorders in type 2 diabetes are less defined. The present study examined the precise developmental process of hyperglycemia and hyperphagia and explored the alterations in the hypothalamic arcuate nucleus (ARC), the primary feeding and metabolic center, in Goto-Kakizaki (GK) rats with type 2 diabetes and nearly normal body weight. At mid 3 to 4 weeks of age, GK rats first exhibited hyperglycemia, and then hyperphagia and reduced mRNA expressions for anorexigenic pro-opiomelanocortin (POMC) and glucokinase in ARC. Furthermore, [Ca2+]i responses to high glucose in ARC POMC neurons were impaired in GK rats at 4 weeks. Treating GK rats from early 3 to mid 6 weeks of age with an anti-diabetic medicine miglitol not only suppressed hyperglycemia but ameliorated hyperphagia and restored POMC mRNA expression in ARC. These results suggest that the early hyperglycemia occurring in weaning period may lead to impaired glucose sensing and neuronal activity of POMC neurons, and thereby induce hyperphagia in GK rats. Correction of hyperglycemia in the early period may prevent and/or ameliorate the progression of hyperphagia in type 2 diabetes.

PROTOCOL: Effects of preventive nutrition interventions among adolescents on health and nutritional status in low- and middle-income countries: a systematic review.

PROTOCOL: Effects of preventive nutrition interventions among adolescents on health and nutritional status in low- and middle-income countries: a systematic review.

Embryonic development of GABAergic terminals in the mouse hypothalamic nuclei involved in feeding behavior

The inhibitory neurotransmitter gamma-amino butyric acid (GABA) plays important roles in energy balance and feeding behavior in the hypothalamus. To reveal the time course of GABAergic network formation, we examined the immunohistochemical localization of glutamic acid decarboxylase (GAD), a GABAergic neuron marker, vesicular GABA transporter (VGAT), a marker of inhibitory terminals, and K+-Cl−-cotransporter2 (KCC2), which shifts GABA action from excitation to inhibition, in the developing mouse hypothalamus. GABAergic terminals, seen as GAD- and VGAT-positive dots, increased in density during embryonic development. Moreover, the onset of KCC2 localization was almost concomitant with GABAergic terminal formation, and KCC2-positive profiles increased in density during development. This suggested that after the formation of GABAergic terminals, GABAergic action may change to inhibition in the hypothalamus. This maturation appears to proceed as follows: the lateral hypothalamus (LH) matures first, followed by the paraventricular nucleus (PVN) by the time of birth, while the ventromedial hypothalamus (VMH) and the arcuate nucleus (Arc) are not fully mature at the time of birth. Our findings suggest that GABAergic networks in the “feeding center” (LH) and the “exit” (PVN) may mature before birth, while those in the “satiety center” (VMH) and “higher control center” (Arc) may mature after birth.

2120

OBJECTIVES/SPECIFIC AIMS: To demonstrate that olanzapine recapitulates the effect of increased lateral hypothalamic (LH) GABAergic activity in the DRN and the DBB. This will provide a potential neural substrate for the observed increase in consumption of food and weight gain. METHODS/STUDY POPULATION: (1) We will examine electrophysiological activity of the DRN and the DBB in response to optogenetic stimulation of LH fibers to these nuclei. (2) We will identify the behavioral phenotype of stimulating these same projections using optogenetic techniques. (3a) Identify the behavioral phenotype of mice possessing cre-loxp-dependent knockout (KO) of LH GABAergic activity, DRN serotonergic activity, and inhibition of DBB cholinergic activity. (3b) Using these mice, we will establish behavioral response to olanzapine in ad libitum feeding and fast-refeeding condition. (4) Using baseline and post-treatment body mass index (BMI), PANSS, and side effect profile scores from a recently completed prospective cohort study of treatment-naive schizophrenic patients receiving atypical antipsychotics for 1 year, we will sequence multiple single nucleotide polymorphisms and explore the correlation of serotonergic, dopaminergic, and cholinergic receptor mutations with the increase in BMI and changes in PANSS score and side effect scores. RESULTS/ANTICIPATED RESULTS: (1) Our preliminary data indicates that the LH exclusively sends GABAergic input to the DBB, and the large majority of its projections to the DRN are GABAergic. (2) We have identified that stimulating LH–>DBB projections produces intense feeding and drinking behavior, a real-time place preference for laser stimulation, and a conditioned place preference for laser stimulation. Preliminary data shows that the LH->DRN also produces feeding behavior. (3a) Our lab has demonstrated that transgenic mice with LH-specific GABA release KO are smaller, have increased anxiety-like behaviors such a repetitive grooming and open field aversion, and have reduced feeding after fasting conditions. We expect the DRN serotonergic KO mice to have increased body weight and reduced anxiety-like behaviors. (3b) Our pilot study demonstrated that the LH GABA KO mice administered olanzapine have a greater consumption of food over 1 hour than controls (n=7, 5, respectively; p=0.08). DRN serotonergic KO mice and mice with inhibition of choline will have an increased baseline feeding behavior, but will not be affected by olanzapine. (4) We believe that SNPs in serotonergic receptors such as 5HT2C, and those affecting dopaminergic and cholinergic receptors, will be more common in schizophrenic patients with increased BMI than those without. Further, we believe that a reduction in the PANSS items reflecting anxiety and aversiveness will correlate with increased BMI, since we postulate that mimicking LH GABAergic activity will produce its previously demonstrated anxiolytic effects. DISCUSSION/SIGNIFICANCE OF IMPACT: Identifying the important role for a reward-oriented feeding center in the brain in producing antipsychotic weight gain will allow a more comprehensive, ethologically sound approach to behavioral modification therapy in these patients. It will lend mechanistic credence to weight control therapies which have used token economy, opioid antagonism, and other inhibition-promoting therapies. This study will also increase the validity for testing further the use of selective serotonin agonists which prevent weight gain such as lorcaserin.

Thiamine content of F-75 therapeutic milk for complicated severe acute malnutrition: time for a change?

Since community-based management of severe acute malnutrition has become the standard of care, the clinical profile of severe acutely malnourished patients admitted to hospitals or inpatient therapeutic feeding centers has changed significantly. These patients are usually very ill and often present with several comorbidities, such as shock, sepsis, and pneumonia. Complicated severe acute malnutrition patients are at risk of thiamine insufficiency, and critically ill patients have higher thiamine requirements. The thiamine content of F-75, the therapeutic milk formula used in the early stabilization phase of refeeding in patients with severe acute malnutrition, seems insufficient. Here, we discuss the need and rationale for a substantial increase in the thiamine content of F-75.

Metabolic and Cardiovascular Actions of Nesfatin-1: Implications in Health and Disease.

Metabolic homeostasis is achieved by proper functioning of a complex endocrine milieu, comprising of signals arising from the brain and peripheral tissues. Our knowledge of the factors regulating such balance is rapidly evolving, as new signaling molecules are being characterized. Of central interest is nesfatin-1, owing to its multifunctional tissue specific actions regulating food intake, body weight, blood glucose and cardiac functions. This review discusses the tissue/system wide distribution and actions of nesfatin-1 in regulating metabolic and cardiovascular functions in healthy conditions and diseases. Nesfatin-1 is an 82 amino acid peptide encoded in the secreted precursor, nucleobinin-2 (NUCB2). It was first reported as a novel anorexigen and a fat reducing orphan ligand. Research to date has established nesfatin-1 in the regulation of food intake via modulation of neuropeptides in the feeding centers of brain. Nesfatin-1 expression was also reported to have a spectrum of peripheral tissue specific actions, which includes insulin secretion (pancreas), fat and glucose modulation (adipocyte), gastric motility and gastric acid secretion (stomach), hormone secretion and transit time (intestine) and mean arterial pressure and cardiac injury (heart). Abnormal levels of nesfatin-1 in circulation and/or variations in tissue specific expression have been observed in obesity, diabetes and cardiovascular diseases. The multifunctional biological actions of nesfatin-1 propelled this peptide as a therapeutic target, and as a potential biomarker of diseases. However, a better and comprehensive understanding of tissue specific effects of nesfatin-1 is critical prior to exploring its possible use in the detection and treatment of diseases.

The outcome of severe acute malnutrition children admitted to nutrition rehabilitation centre of a tertiary level care hospital

Background: Malnutrition is common in paediatric age group and is responsible for high morbidity, mortality and serious long term sequelae. A nutritional therapy followed by nutritional rehabilitation is a very important aspect for these children. Optimal management of these acutely ill children and a good outcome depends on an evidence based regimen of care in the Nutritional Rehabilitation Centre (NRC). We under took this study to know the outcome of SAM children admitted to the NRC of our hospital.Methods: 736 children were enrolled in the study. Data of the children like age, sex, criteria for admission, associated complications, feeding pattern, response to therapy and their outcome were evaluated.Results: female were 371 (50.40%) and male were 365(49.5%) children. 221 (30.02%) were <6months, 231(31.38%) 6-12months, 144 (19.56%) 12months-24months and 140(19.02%) were >2 years. The weight for height of all the children were less than -3SD. 72.9% of the children had complication, diarrhoea in 28.49% and pneumonia in 35.75% were the common complications. 513 (74.55%) children showed some weight gain. The mean weight gain was 4.4 gm/kg/day. Mean duration of stay was 8.45 days. Cure rate was 81% and death rate was 6.52%.Conclusions: With a cure rate of 81%, death rate of 6.52% and defaulter rate of 12.09%, falling within the acceptable range and duration of stay 8.4 days, weight gain of 4.4g/kg/days in the lower range, management of these children in specialised feeding centre is important for faster recovery and a better weight gain.

Sweet taste receptor in the hypothalamus: a potential new player in glucose sensing in the hypothalamus.

The hypothalamic feeding center plays an important role in energy homeostasis. The feeding center senses the systemic energy status by detecting hormone and nutrient levels for homeostatic regulation, resulting in the control of food intake, heat production, and glucose production and uptake. The concentration of glucose is sensed by two types of glucose-sensing neurons in the feeding center: glucose-excited neurons and glucose-inhibited neurons. Previous studies have mainly focused on glucose metabolism as the mechanism underlying glucose sensing. Recent studies have indicated that receptor-mediated pathways also play a role in glucose sensing. This review describes sweet taste receptors in the hypothalamus and explores the role of sweet taste receptors in energy homeostasis.

Activation of the hypothalamic feeding centre upon visual prey detection

The visual system plays a major role in food/prey recognition in diurnal animals, and food intake is regulated by the hypothalamus. However, whether and how visual information about prey is conveyed to the hypothalamic feeding centre is largely unknown. Here we perform real-time imaging of neuronal activity in freely behaving or constrained zebrafish larvae and demonstrate that prey or prey-like visual stimuli activate the hypothalamic feeding centre. Furthermore, we identify prey detector neurons in the pretectal area that project to the hypothalamic feeding centre. Ablation of the pretectum completely abolishes prey capture behaviour and neurotoxin expression in the hypothalamic area also reduces feeding. Taken together, these results suggest that the pretecto-hypothalamic pathway plays a crucial role in conveying visual information to the feeding centre. Thus, this pathway possibly converts visual food detection into feeding motivation in zebrafish.

Transcriptome analysis of tetrodotoxin sensing and tetrodotoxin action in the central nervous system of tiger puffer Takifugu rubripes juveniles

To reveal the sensing of tetrodotoxin (TTX) by tiger puffer Takifugu rubripes juveniles and its action in the central nervous system (CNS), we conducted transcriptome analysis using next-generation sequencing for the olfactory system and brain of non-toxic cultured juveniles administered TTX. Sixty-seven million reads from the nasal region (olfactory epithelium and skin) and the brain of each of three individuals of the control, TTX-sensing and TTX-administered juveniles were assembled into 153,958 contigs. Mapping raw reads from each sample onto the nucleotide sequences of predicted transcripts in the T. rubripes genome (FUGU version 4) and the de novo assembled contigs to investigate their frequency of expression revealed that the expression of 21 and 81 known genes significantly changed in TTX-sensing and TTX-administered juveniles in comparison with control juveniles, respectively. These genes included those related to feeding regulation and a reward system, and indicated that TTX ingestion of T. rubripes juveniles is controlled in the feeding center in the brain, that T. rubripes may sense TTX as a reward, and that accumulated TTX directly acts on the central nervous system to adjust TTX ingestion.

Local-food-based complementary feeding for the nutritional status of children ages 6-36 months in rural areas of Indonesia.

PurposeThis study aimed to evaluate a pilot project of the Nursing Feeding Center “Posyandu Plus” (NFCPP) through local food-based complementary feeding (LFCF) program designed to improve the nutritional status of children aged 6–36 months at community health centers in Indonesia.MethodsA quasi-experimental design was used to obtain data regarding the nutritional status of 109 children who participated in the project from 6 rural areas. The NFCPP was conducted for 9 weeks, comprising 2 weeks of preintervention, 6 weeks of intervention, and one week of postintervention. The LFCF intervention consisted of 12 sets of recipes to be made by mothers and given to their children 4 times daily over 6 weeks. The weight-for-age z score (WAZ), height-for-age z score (HAZ), weight-for-height z score (WHZ), and body mass index-for-age z score (BAZ) were calculated using World Health Organization Anthro Plus version 1.0.3.ResultsLFCF intervention significantly increased WHZ, WAZ, and BAZ scores but decreased HAZ scores (P<0.001). Average scores of WHZ (0.96±0.97) and WAZ (0.45±0.72) increased; BAZ increased (1.12±0.93) after 6 weeks of LFCF. WAZ scores postintervention were 50.5% of normal, and WHZ scores were 77.1% of normal. However, the HAZ score decreased by 0.53±0.52, which indicated 57.8% had short stature.ConclusionThe NFCPP program with LFCF intervention can improve the nutritional status of children in rural areas. It should be implemented as a sustained program for better provision of complementary feeding during the period of lactation using local food made available at community health centers.