Leptin and Obesity: Role and Clinical Implication.

The peptide hormone leptin regulates food intake, body mass, and reproductive function and plays a role in fetal growth, proinflammatory immune responses, angiogenesis and lipolysis. Leptin is a product of the obese (ob) gene and, following synthesis and secretion from fat cells in white adipose tissue, binds to and activates its cognate receptor, the leptin receptor (LEP-R). LEP-R distribution facilitates leptin's pleiotropic effects, playing a crucial role in regulating body mass via a negative feedback mechanism between adipose tissue and the hypothalamus. Leptin resistance is characterized by reduced satiety, over-consumption of nutrients, and increased total body mass. Often this leads to obesity, which reduces the effectiveness of using exogenous leptin as a therapeutic agent. Thus, combining leptin therapies with leptin sensitizers may help overcome such resistance and, consequently, obesity. This review examines recent data obtained from human and animal studies related to leptin, its role in obesity, and its usefulness in obesity treatment.

Impact of a prenatal education intervention in pregnant women to prevent overweight in infants.

INTRODUCTION: During the first 1000 days of life is the basis for a child's future health established. OBJECTIVE: To evaluate the impact of a prenatal educational intervention in pregnant women on the nutritional status of the child from birth to 4 months of age. METHODS: Quasi-experimental intervention design in women with at least 12 weeks of gestation, who were randomly assigned to an intervention group (IG) to participate in five group and three individual sessions on feeding practices and maternal perception of the child's weight and signals of hunger-satiety; the control group (CG) received routine care that included at least three prenatal consultations. RESULTS: Thirty women were included in each group. After the intervention, women in the CG practiced less exclusive breastfeeding, were more likely to underestimate or overestimate the children's weight, and perceived hunger-satiety signals with less intensity (p < 0.05). 80 % of the infants in the IG had normal weight, whereas 63 % of those in the CG had a combination of overweight and obesity (p < 0.05). CONCLUSIONS: The prenatal education program in pregnant women showed a significant effect on postnatal nutritional status of infants four months after birth.

INTRODUCCIÓN: Durante los primeros 1000 días de vida se establece la base para la salud futura de un niño. OBJETIVO: Evaluar el impacto de una intervención educativa prenatal en mujeres embarazadas sobre el estado nutricional del hijo desde el nacimiento hasta los cuatro meses de edad. MÉTODOS: Diseño cuasiexperimental de intervención con mujeres a partir de la semana 12 de gestación, asignadas aleatoriamente a un grupo de intervención (GI) para recibir cinco sesiones grupales y tres individuales sobre prácticas de alimentación y percepción materna del peso del hijo y de señales de hambre-saciedad; el grupo control (GC) recibió atención de rutina que incluía al menos tres consultas prenatales. RESULTADOS: 30 mujeres conformaron cada grupo. Después de la intervención, las mujeres del GC practicaron menos lactancia materna exclusiva, fueron propensas a subestimar o sobrestimar el peso del hijo y percibieron con menor intensidad las señales de hambre-saciedad (p < 0.05). El 80 % de los lactantes del GI presentaron peso normal y 63 % de los niños del GC, una combinación de sobrepeso y obesidad (p < 0.05). CONCLUSIONES: El programa de educación prenatal en mujeres embarazadas mostró un efecto significativo en el estado nutricional de los lactantes después de cuatro meses del nacimiento.

Central and peripheral GLP-1 systems independently suppress eating.

The anorexigenic peptide glucagon-like peptide-1 (GLP-1) is secreted from gut enteroendocrine cells and brain preproglucagon (PPG) neurons, which, respectively, define the peripheral and central GLP-1 systems. PPG neurons in the nucleus tractus solitarii (NTS) are widely assumed to link the peripheral and central GLP-1 systems in a unified gut-brain satiation circuit. However, direct evidence for this hypothesis is lacking, and the necessary circuitry remains to be demonstrated. Here we show that PPGNTS neurons encode satiation in mice, consistent with vagal signalling of gastrointestinal distension. However, PPGNTS neurons predominantly receive vagal input from oxytocin-receptor-expressing vagal neurons, rather than those expressing GLP-1 receptors. PPGNTS neurons are not necessary for eating suppression by GLP-1 receptor agonists, and concurrent PPGNTS neuron activation suppresses eating more potently than semaglutide alone. We conclude that central and peripheral GLP-1 systems suppress eating via independent gut-brain circuits, providing a rationale for pharmacological activation of PPGNTS neurons in combination with GLP-1 receptor agonists as an obesity treatment strategy.

Impacto de una intervención de educación prenatal en mujeres embarazadas para prevenir el sobrepeso en lactantes / Impact of a prenatal education intervention in pregnant women to prevent overweight in infants

Resumen Introducción: Durante los primeros 1000 días de vida se establece la base para la salud futura de un niño. Objetivo: Evaluar el impacto de una intervención educativa prenatal en mujeres embarazadas sobre el estado nutricional del hijo desde el nacimiento hasta los cuatro meses de edad. Métodos: Diseño cuasiexperimental de intervención con mujeres a partir de la semana 12 de gestación, asignadas aleatoriamente a un grupo de intervención (GI) para recibir cinco sesiones grupales y tres individuales sobre prácticas de alimentación y percepción materna del peso del hijo y de señales de hambre-saciedad; el grupo control (GC) recibió atención de rutina que incluía al menos tres consultas prenatales. Resultados: 30 mujeres conformaron cada grupo. Después de la intervención, las mujeres del GC practicaron menos lactancia materna exclusiva, fueron propensas a subestimar o sobrestimar el peso del hijo y percibieron con menor intensidad las señales de hambre-saciedad (p < 0.05). El 80 % de los lactantes del GI presentaron peso normal y 63 % de los niños del GC, una combinación de sobrepeso y obesidad (p < 0.05). Conclusiones: El programa de educación prenatal en mujeres embarazadas mostró un efecto significativo en el estado nutricional de los lactantes después de cuatro meses del nacimiento.

Abstract Introduction: During the first 1000 days of life is the basis for a child‘s future health established. Objective: To evaluate the impact of a prenatal educational intervention in pregnant women on the nutritional status of the child from birth to 4 months of age. Methods: Quasi-experimental intervention design in women with at least 12 weeks of gestation, who were randomly assigned to an intervention group (IG) to participate in five group and three individual sessions on feeding practices and maternal perception of the child’s weight and signals of hunger-satiety; the control group (CG) received routine care that included at least three prenatal consultations. Results: Thirty women were included in each group. After the intervention, women in the CG practiced less exclusive breastfeeding, were more likely to underestimate and overestimate the children’s weight, and perceived hunger-satiety signals with less intensity (p < 0.05). 80 % of the infants in the IG had normal weight, whereas 63 % of those in the CG had a combination of overweight and obesity (p < 0.05). Conclusions: The prenatal education program in pregnant women showed a significant effect on postnatal nutritional status of infants four months after birth.

Changes in Ghrelin and Glucagon following a Low Glycemic Load Diet in Women with PCOS.

CONTEXT: Altered satiety hormones in women with polycystic ovarian syndrome (PCOS) may contribute to obesity. Diets with a low glycemic load (GL) may influence appetite-regulating hormones including glucagon and ghrelin. OBJECTIVE: To test the hypothesis that following a 4-week, eucaloric low vs high GL diet habituation, a low vs high GL meal will increase glucagon and decrease ghrelin to reflect greater satiety and improve self-reported fullness. METHODS: Secondary analysis of a randomized crossover trial. PARTICIPANTS: Thirty women diagnosed with PCOS. INTERVENTION: Participants were provided low (41:19:40% energy from carbohydrate:protein:fat) and high (55:18:27) GL diets for 8 weeks each. At each diet midpoint, a solid meal test was administered to examine postprandial ghrelin, glucagon, glucose, insulin, and self-reported appetite scores. RESULTS: After 4 weeks, fasting glucagon was greater with the low vs high GL diet (P = .035), and higher fasting glucagon was associated with lesser feelings of hunger (P = .009). Significant diet effects indicate 4-hour glucagon was higher (P < .001) and ghrelin was lower (P = .009) after the low vs high GL meal. A trending time × diet interaction (P = .077) indicates feelings of fullness were greater in the early postprandial phase after the high GL meal, but no differences were observed the late postprandial phase. CONCLUSION: These findings suggest after low GL diet habituation, a low GL meal reduces ghrelin and increases glucagon in women with PCOS. Further research is needed to determine the influence of diet composition on ad libitum intake in women with PCOS.

A Pilot Study of Gut-Brain Signaling After Octreotide Therapy for Unintentional Weight Loss After Esophagectomy.

BACKGROUND: Recurrence-free patients after esophageal cancer surgery face long-term nutritional consequences, occurring in the context of an exaggerated postprandial gut hormone response. Acute gut hormone suppression influences brain reward signaling and eating behavior. This study aimed to suppress gut hormone secretion and characterize reward responses and eating behavior among postesophagectomy patients with unintentional weight loss. METHODS: This pilot study prospectively studied postoperative patients with 10% or greater body weight loss (BWL) beyond 1 year who were candidates for clinical treatment with long-acting octreotide (LAR). Before and after 4 weeks of treatment, gut hormone secretion, food cue reactivity (functional magnetic resonance imaging), eating motivation (progressive ratio task), ad libitum food intake, body composition, and symptom burden were assessed. RESULTS: Eight patients (7 male, age: mean ±â€…SD 62.8 ±â€…9.4 years, postoperative BWL: 15.5 ±â€…5.8%) participated. Octreotide LAR did not significantly suppress total postprandial plasma glucagon-like peptide-1 response at 4 weeks (P = .08). Postprandial symptom burden improved after treatment (Sigstad score median [range]: 12 [2-28] vs 8 [3-18], P = .04) but weight remained stable (pre: 68.6 ±â€…12.8 kg vs post: 69.2 ±â€…13.4 kg, P = .13). There was no significant change in brain reward system responses, during evaluation of high-energy or low-energy food pictures, nor their appeal rating. Moreover, treatment did not alter motivation to eat (P = .41) nor ad libitum food intake(P = .46). CONCLUSION: The protocol used made it feasible to characterize the gut-brain axis and eating behavior in this cohort. Inadequate suppression of gut hormone responses 4 weeks after octreotide LAR administration may explain the lack of gut-brain pathway alterations. A higher dose or shorter interdose interval may be required to optimize the intervention.

Estrogen and gut satiety hormones in vagus-hindbrain axis.

Estrogens modulate different physiological functions, including reproduction, inflammation, bone formation, energy expenditure, and food intake. In this review, we highlight the effect of estrogens on food intake regulation and the latest literature on intracellular estrogen signaling. In addition, gut satiety hormones, such as cholecystokinin, glucagon-like peptide 1 and leptin are essential to regulate ingestive behaviors in the postprandial period. These peripheral signals are sensed by vagal afferent terminals in the gut wall and transmitted to the hindbrain axis. Here we 1. review the role of the vagus-hindbrain axis in response to gut satiety signals and 2. consider the potential synergistic effects of estrogens on gut satiety signals at the level of vagal afferent neurons and nuclei located in the hindbrain. Understanding the action of estrogens in gut-brain axis provides a potential strategy to develop estrogen-based therapies for metabolic diseases and emphasizes the importance of sex difference in the treatment of obesity.

Free Fatty Acid-Induced Peptide YY Expression Is Dependent on TG Synthesis Rate and Xbp1 Splicing.

Gut-derived satiety hormones provide negative feedback to suppress food intake and maintain metabolic function in peripheral tissues. Despite the wealth of knowledge of the systemic effects of these hormones, very little is known concerning the mechanisms by which nutrients, such as dietary fats, can promote the expression of genes involved in L-cell hormone production. We have tested the role of various dietary fats and found that after hydrolysis into free fatty acids (FFA's), there is a differential response in the extent to which they induce PYY gene and protein production. The effect of FFA's also seems to relate to triglyceride (TG) re-esterification rate, with MUFA re-esterifying faster with lower PYY production. We have also found that there are differences in potency of FFA's based on their desaturation patterns in vitro. The potency effect of FFA's is influenced by the rate of TG re-esterification, such that the longer FFA's are in contact with L-cells, the more PYY they produce. We found that chronic consumption of high-fat diets enables the small intestine to re-esterify FFA's into TG faster and earlier which resulted in a blunted postprandial PYY response. Lastly, we found that FFA's induce X-box-binding protein-1 activation (Xbp1s) in L-cells and that adenoviral delivery of Xbp1s was sufficient to induce PYY gene expression. Taken together, the present work indicates that dietary fat can induce satiety, in part, prior to re-esterification. Chronic high-fat diet consumption increases the rate of re-esterification which diminishes satiety and may lead to increased food intake. Targeting intestinal TG synthesis may prove beneficial in restoring obesity-associated reductions in postprandial satiety.

Baby-led weaning, an overview of the new approach to food introduction: integrative literature review / Baby-led weaning, panorama da nova abordagem sobre introdução alimentar: revisão integrativa de literatura

ABSTRACT Objective: To analyze the scientific literature on Baby-Led Weaning with an integrative literature review to identify risks and benefits. Data source: The databases used were: National Library of Medicine (MEDLINE), Latin American and Caribbean Literature in Health Sciences (LILACS - Literatura Latino-Americana e do Caribe em Ciências da Saúde), US National Library of Medicine (PubMed), and Virtual Health Library (BVS - Biblioteca Virtual em Saúde) in December 2017. The inclusion criteria established were publications in English with the descriptor "baby-led weaning" in the heading, abstract, or keywords, classified as original articles, of primary nature, and available online and in full. We excluded review articles, editorials, letters to the editor, critical commentaries, and books on the subject, as well as articles not available in full and duplicates. Data summary: We identified 106 articles, of which 17 met the selection criteria. The Baby-Led Weaning method was significantly associated with the baby's satiety, the start of complementary feeding, and adequacy of weight gain. On the other hand, choking and the intake of micronutrients were negatively associated, however with no statistical differences. Conclusions: Despite the benefits found, the risks still deserve attention and should be investigated with longitudinal randomized controlled studies to ensure the safety of the method when practiced exclusively.

RESUMO Objetivo: Analisar a literatura científica referente ao desmame guiado pelo bebê (Baby-Led Weaning) por meio de revisão integrativa de literatura a fim de identificar riscos e benefícios. Fonte de dados: As bases de dados utilizadas foram: National Library of Medicine (MEDLINE), Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS), US National Library of Medicine (PubMed) e Biblioteca Virtual em Saúde (BVS); e a busca foi realizada em dezembro de 2017. Os critérios de inclusão estabelecidos foram publicações em inglês com o descritor "baby-led weaning" no título, resumo ou palavras-chave em artigos classificados como originais de natureza primária, disponibilizados online e na íntegra. Excluíram-se artigos de revisão, editoriais, cartas ao editor, comentários críticos e livros abordando o assunto, assim como artigos não disponíveis na íntegra e duplicatas. Síntese dos dados: Identificaram-se 106 artigos, dos quais 17 faziam parte do critério de seleção. O método Baby-Led Weaning teve associação significativa com a saciedade do bebê, início da alimentação complementar e adequação de ganho de peso. Já o engasgo e a ingestão de micronutrientes foram associados negativamente, contudo sem diferenças estatísticas. Conclusões: Apesar dos benefícios apontados, os riscos ainda merecem atenção por meio de pesquisas longitudinais controladas e randomizadas para fornecer mais segurança para a sua prática de forma exclusiva.

Anorectic response to the trichothecene T-2 toxin correspond to plasma elevations of the satiety hormone glucose-dependent insulinotropic polypeptide and peptide YY3-36.

T-2 toxin, a potent type A trichothecene mycotoxin, is produced by various Fusarium species and can negatively impact animal and human health. Although anorexia induction is a common hallmark of T-2 toxin-induced toxicity, the underlying mechanisms for this adverse effect are not fully understood. The goal of this study was to determine the roles of two gut satiety hormones, glucose-dependent insulinotropic polypeptide (GIP) and Peptide YY3-36 (PYY3-36) in anorexia induction by T-2 toxin. Elevations of plasma GIP and PYY3-36 markedly corresponded to anorexia induction following oral exposure to T-2 toxin using a nocturnal mouse anorexia model. Direct administration of exogenous GIP and PYY3-36 similarly induced anorectic responses. Furthermore, the GIP receptor antagonist Pro3GIP dose-dependently attenuated both GIP- and T-2 toxin-induced anorectic responses. Pretreatment with NPY2 receptor antagonist JNJ-31020028 induced a dose-dependent attenuation of both PYY3-36- and T-2 toxin-induced anorectic responses. To summarize, these findings suggest that both GIP and PYY3-36 might be critical mediators of anorexia induction by T-2 toxin.

Neuronal connections of the central amygdalar nucleus with refeeding-activated brain areas in rats.

Following fasting, satiety is accompanied by neuronal activation in brain areas including the central amygdalar nucleus (CEA). Since CEA is known to inhibit food intake, we hypothesized that CEA contributes to the termination of meal during refeeding. To better understand the organization of this satiety-related circuit, the interconnections of the CEA with refeeding-activated neuronal groups were elucidated using retrograde (cholera toxin-ß subunit, CTB) and anterograde (phaseolus vulgaris leucoagglutinin, PHA-L) tracers in male rats. C-Fos-immunoreactivity was used as marker of neuronal activation. The refeeding-activated input of the CEA primarily originated from the paraventricular thalamic, parasubthalamic and parabrachial nuclei. Few CTB-c-Fos double-labeled neurons were detected in the prefrontal cortex, lateral hypothalamic area, nucleus of the solitary tract (NTS) and the bed nuclei of the stria terminalis (BNST). Only few refeeding-activated proopiomelanocortin-producing neurons of the arcuate nucleus projected to the CEA. Anterograde tract tracing revealed a high density of PHAL-labeled axons contacted with refeeding-activated neurons in the BNST, lateral hypothalamic area, parasubthalamic, paraventricular thalamic and parabrachial nuclei and NTS; a low density of labeled axons was found in the paraventricular hypothalamic nucleus. Chemogenetic activation of the medial CEA (CEAm) inhibited food intake during the first hour of refeeding, while activation of lateral CEA had no effect. These data demonstrate the existence of reciprocal connections between the CEA and distinct refeeding-activated hypothalamic, thalamic and brainstem nuclei, suggesting the importance of short feedback loops in the regulation of satiety and importance of the CEAm in the regulation of food intake during refeeding.

Saciación vs saciedad: reguladores del consumo alimentario / Satiation and satiety in the regulation of energy intake

The study of the factors that regulate high energy food intake is especially relevant nowadays due to the high prevalence of overweight and obesity. Food intake regulation can be divided in two basic processes, namely satiation and satiety. Satiation is the process that determines the moment in which feeding stops and regulates the amount of ingested food during a single meal. Satiety is the interval between meals and regulates the time elapsed between two meals. The longer the interval, the lower energy intake. Each of these processes are regulated by different factors, which are here reviewed.

Lipid stimulation of fatty acid sensors in the human duodenum: relationship with gastrointestinal hormones, BMI and diet.

BACKGROUND AND AIMS: The small intestinal free fatty acid (FFA) sensors, FFA receptor 1 (FFAR1), FFAR4, G-protein receptor 119 (GPR119) and cluster of differentiation-36 (CD36), mediate the fat-induced release of gastrointestinal (GI) hormones. We investigated whether expression of duodenal FFA sensors in humans was (i) altered by intraduodenal (ID) lipid infusion, (ii) disordered in overweight or obese individuals, (iii) related to lipid-induced GI hormone secretion or (iv) affected by habitual dietary patterns. METHODS: Endoscopic duodenal biopsies were collected from 20 lean (body mass index (BMI): 22±1 kg m-2), 18 overweight (BMI: 27±1 kg m-2) and 19 obese (BMI: 35±1 kg m-2) participants at baseline, and following a 30 min ID Intralipid infusion (2 kcal min-1); FFA sensor expression was quantified by reverse transcription-PCR. On a separate day, participants underwent ID Intralipid infusion (2 kcal min-1) for 120 min, to assess GI hormone responses. Habitual diet was evaluated using food frequency questionnaires. RESULTS: Baseline FFAR1 and FFAR4 expression were lower, and CD36 was higher, in obese participants compared with lean participants. ID lipid increased GPR119 and FFAR1 expression equally across study groups, but did not alter FFAR4 or CD36 expression. Increased FFAR1 expression correlated positively with glucose-dependent insulinotropic polypeptide (GIP) secretion (r=0.3, P<0.05), whereas there was no relationship between habitual diet with the expression of FFA sensors. CONCLUSIONS: Obesity is associated with altered duodenal expression of FFAR1, FFAR4 and CD36, suggesting altered capacity for the sensing, absorption and metabolism, of dietary lipids. GPR119 and FFAR1 are early transcriptional responders to the presence of ID lipid, whereas FFAR1 may be an important trigger for lipid-induced GIP release in humans.

Weight Loss, Satiety, and the Postprandial Gut Hormone Response After Esophagectomy: A Prospective Study.

OBJECTIVE: To prospectively characterize changes in body weight, satiety, and postprandial gut hormone profiles following esophagectomy. BACKGROUND: With improved oncologic outcomes in esophageal cancer, there is an increasing focus on functional status and health-related quality of life in survivorship. Early satiety and weight loss are common after esophagectomy, but the pathophysiology of these phenomena remains poorly understood. METHODS: In this prospective study, consecutive patients undergoing esophagectomy with gastric conduit reconstruction were studied preoperatively and at 10 days, 6 weeks, and 3 months postoperatively. Glucagon-like peptide 1 (GLP-1) immunoreactivity of plasma collected immediately before and at 15, 30, 60, 90, 120, 150, and 180 minutes after a standardized 400-kcal mixed meal was determined. Gastrointestinal symptom scores were computed using European Organization for Research and Treatment of Cancer questionnaires. RESULTS: Body weight loss at 6 weeks and 3 months postoperatively among 13 patients undergoing esophagectomy was 11.1 ±â€Š2.3% (P < 0.001) and 16.3 ±â€Š2.2% (P < 0.0001), respectively. Early satiety (P = 0.043), gastrointestinal pain and discomfort (P = 0.01), altered taste (P= 0.006), and diarrhea (P= 0.038) scores increased at 3 months postoperatively. Area under the curve for the satiety gut hormone GLP-1 was significantly increased from 10 days postoperatively (2.4 ±â€Š0.2-fold increase, P < 0.01), and GLP-1 peak increased 3.8 ±â€Š0.6-, 4.7 ±â€Š0.8-, and 4.4 ±â€Š0.5-fold at 10 days, 6 weeks, and 3 months postoperatively (all P < 0.0001). Three months postoperatively, GLP-1 area under the curve was associated with early satiety (P = 0.0002, R = 0.74), eating symptoms (P = 0.007, R = 0.54), and trouble enjoying meals (P = 0.0004, R = 0.73). CONCLUSIONS: After esophagectomy, patients demonstrate an exaggerated postprandial satiety gut hormone response, which may mediate postoperative changes in satiety, body weight, and gastrointestinal quality of life.

A cholinergic basal forebrain feeding circuit modulates appetite suppression.

Atypical food intake is a primary cause of obesity and other eating and metabolic disorders. Insight into the neural control of feeding has previously focused mainly on signalling mechanisms associated with the hypothalamus, the major centre in the brain that regulates body weight homeostasis. However, roles of non-canonical central nervous system signalling mechanisms in regulating feeding behaviour have been largely uncharacterized. Acetylcholine has long been proposed to influence feeding owing in part to the functional similarity between acetylcholine and nicotine, a known appetite suppressant. Nicotine is an exogenous agonist for acetylcholine receptors, suggesting that endogenous cholinergic signalling may play a part in normal physiological regulation of feeding. However, it remains unclear how cholinergic neurons in the brain regulate food intake. Here we report that cholinergic neurons of the mouse basal forebrain potently influence food intake and body weight. Impairment of cholinergic signalling increases food intake and results in severe obesity, whereas enhanced cholinergic signalling decreases food consumption. We found that cholinergic circuits modulate appetite suppression on downstream targets in the hypothalamus. Together our data reveal the cholinergic basal forebrain as a major modulatory centre underlying feeding behaviour.

Dorsomedial hypothalamic NPY affects cholecystokinin-induced satiety via modulation of brain stem catecholamine neuronal signaling.

Increased neuropeptide Y (NPY) gene expression in the dorsomedial hypothalamus (DMH) has been shown to cause hyperphagia, but the pathway underlying this effect remains less clear. Hypothalamic neural systems play a key role in the control of food intake, in part, by modulating the effects of meal-related signals, such as cholecystokinin (CCK). An increase in DMH NPY gene expression decreases CCK-induced satiety. Since activation of catecholaminergic neurons within the nucleus of solitary tract (NTS) contributes to the feeding effects of CCK, we hypothesized that DMH NPY modulates NTS neural catecholaminergic signaling to affect food intake. We used an adeno-associated virus system to manipulate DMH NPY gene expression in rats to examine this pathway. Viral-mediated hrGFP anterograde tracing revealed that DMH NPY neurons project to the NTS; the projections were in close proximity to catecholaminergic neurons, and some contained NPY. Viral-mediated DMH NPY overexpression resulted in an increase in NPY content in the NTS, a decrease in NTS tyrosine hydroxylase (TH) expression, and reduced exogenous CCK-induced satiety. Knockdown of DMH NPY produced the opposite effects. Direct NPY administration into the fourth ventricle of intact rats limited CCK-induced satiety and overall TH phosphorylation. Taken together, these results demonstrate that DMH NPY descending signals affect CCK-induced satiety, at least in part, via modulation of NTS catecholaminergic neuronal signaling.

Beyond expectations: the physiological basis of sensory enhancement of satiety.

BACKGROUND/OBJECTIVES: Consumption of high-energy beverages has been implicated as a risk factor for weight gain, yet why nutrients ingested as beverages fail to generate adequate satiety remains unclear. In general, consumers do not expect drinks to be satiating, but drinks generate greater satiety when their sensory characteristics imply they may be filling. These findings challenge traditional bottom-up models of how gut-based satiety signals modify behaviour to suggest that beliefs at the point of ingestion modify gut-based satiety signalling. SUBJECTS/METHODS: Healthy volunteers (n=23) consumed four different beverages, combining an overt sensory manipulation (thin, low sensory (LS) or thicker and more creamy, enhanced sensory (ES)) and covert nutrient manipulation (low energy (LE), 78 kcal; high energy (HE), 267 kcal) on different days. Effects on satiety were assessed through rated appetite and levels of glucose, insulin, pancreatic polypeptide (PP) and cholesystokinin (CCK) recorded periodically over 90 min, and through intake at an ad libitum test lunch. RESULTS: Intake at the test lunch and rated appetite were both altered by both the sensory and nutrient manipulations, with lowest intake and greatest suppression of hunger post-drink in the ESHE condition. Insulin increased more after HE than LE drinks, and after ES than LS drinks, whereas PP levels were higher after ES than LS versions. CCK levels only increased after the ESHE drink. CONCLUSIONS: These data confirm acute sensitivity of satiety after consuming a drink both to the sensory characteristics and nutrient content of the drink, and suggest that this may be, at least in part, due to top-down modulation of release of satiety-related gut hormones.

Compared to Sleeve Gastrectomy, Duodenal-Jejunal Bypass with Sleeve Gastrectomy Gives Better Glycemic Control in T2DM Patients, with a Lower ß-Cell Response and Similar Appetite Sensations: Mixed-Meal Study.

BACKGROUND: Functional studies of how duodenal-jejunal exclusion (DJE) brings a superior glycemic control when added to sleeve gastrectomy in duodenal-jejunal bypass with sleeve gastrectomy (DJB-SG) patients, are lacking. To study this, we compared the appetite sensations and the ß-cell response following a standard mixed meal in patients with DJB-SG, versus those with sleeve gastrectomy (SG) alone. METHODS: Twenty one patients who underwent DJB-SG and 25 with SG, who participated in mixed-meal tests (MMTT) preoperatively and at 1 year, with complete data were included and compared. Blood glucose, C-peptide, and insulin levels were estimated, along with the visual analogue scale (VAS) scoring of the six appetite sensations, as a part of the MMTT. RESULTS: At 1 year following surgery, compared to SG group, DJB-SG group had greater complete remission rates (HbA1C <6.0 %) of 62 versus 32 % (p < 0.05), with similar total body weight loss (25.7 vs. 22 %). There were significantly lower post-prandial blood glucose and lower C-peptide levels during the MMTT in the patients with DJB-SG compared to SG group. There were no significant differences in the appetite sensations (mean VAS) scores between the groups. CONCLUSION: The addition of DJE component to SG, as in DJB-SG, was associated with higher diabetes remission rates, lower glycemic fluctuations, and lower C-peptide levels. This may point to a ß-cell preserving glucose control which could result in longer remission of type 2 diabetes mellitus (T2DM). This effect also may be unrelated to food intake as there were no significant differences in the appetite sensations.