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.

Effect of White Potatoes on Subjective Appetite, Food Intake, and Glycemic Response in Healthy Older Adults.

The objective of this study was to determine the effect of white potato cooking methods on subjective appetite, short-term food intake (FI), and glycemic response in healthy older adults. Using a within-subject, repeated-measures design, 20 participants (age: 70.4 ± 0.6 y) completed, in random order, five treatment conditions: three potato treatments (baked potatoes, mashed potatoes, and French fries), an isocaloric control treatment (white bread), or a fasting condition (meal skipping). Subjective appetite and glycemic response were measured for 120 min using visual analogue scales and capillary blood samples, respectively. Lunch FI was measured with an ad libitum pizza meal at 120 min. Change from baseline subjective appetite (p < 0.001) and lunch FI (p < 0.001) were lower after all test treatments compared with meal skipping (p < 0.001), but did not differ among test treatments. Cumulative FI (test treatment + lunch FI) did not differ among treatment conditions. Blood glucose concentrations were higher after all test treatments compared with meal skipping (p < 0.001), but were not different from each other. In healthy older adults, white potatoes suppressed subjective appetite and lunch FI compared with meal skipping, suggesting white potatoes do not bypass regulatory control mechanisms of FI.

Effects of hunger, satiety and oral glucose on effective connectivity between hypothalamus and insular cortex.

The hypothalamus and insular cortex play an essential role in the integration of endocrine and homeostatic signals and their impact on food intake. Resting-state functional connectivity alterations of the hypothalamus, posterior insula (PINS) and anterior insula (AINS) are modulated by metabolic states and caloric intake. Nevertheless, a deeper understanding of how these factors affect the strength of connectivity between hypothalamus, PINS and AINS is missing. This study investigated whether effective (directed) connectivity within this network varies as a function of prandial states (hunger vs. satiety) and energy availability (glucose levels and/or hormonal modulation). To address this question, we measured twenty healthy male participants of normal weight twice: once after 36 â€‹h of fasting (except water consumption) and once under satiated conditions. During each session, resting-state functional MRI (rs-fMRI) and hormone concentrations were recorded before and after glucose administration. Spectral dynamic causal modeling (spDCM) was used to assess the effective connectivity between the hypothalamus and anterior and posterior insula. Using Bayesian model selection, we observed that the same model was identified as the most likely model for each rs-fMRI recording. Compared to satiety, the hunger condition enhanced the strength of the forward connections from PINS to AINS and reduced the strength of backward connections from AINS to PINS. Furthermore, the strength of connectivity from PINS to AINS was positively related to plasma cortisol levels in the hunger condition, mainly before glucose administration. However, there was no direct relationship between glucose treatment and effective connectivity. Our findings suggest that prandial states modulate connectivity between PINS and AINS and relate to theories of interoception and homeostatic regulation that invoke hierarchical relations between posterior and anterior insula.

Metabolic Lateralization in the Hypothalamus of Male Rats Related to Reproductive and Satiety States.

The hypothalamus is the main regulatory center of many homeostatic processes, such as reproduction, food intake, and sleep-wake behavior. Recent findings show that there is a strongly interdependent side-linked localization of hypothalamic functions between the left and right hemispheres. The goal of the present study was to trace functional asymmetry of the hypothalamus related to the regulation of food intake and reproduction, in male rodents. Subjects were examined through measurements of mitochondrial metabolism ex vivo. Impact of gonadectomy and scheduled feeding was tested on the modulation of hypothalamic metabolic asymmetry. Results show that in male rats, functional lateralization of the hypothalamus can be attributed to the satiety state rather than to reproductive control. Fasting caused left-sided metabolic dominance, while satiety was linked to the right hemisphere; trends and direction in sided dominance gradually followed the changes in satiety state. Our findings revealed satiety state-dependent metabolic differences between the two hypothalamic hemispheres. It is therefore concluded that, at least in male rats, the hypothalamic hemispheres control the satiety state-related functions in an asymmetric manner.

BABY-LED WEANING, AN OVERVIEW OF THE NEW APPROACH TO FOOD INTRODUCTION: INTEGRATIVE LITERATURE REVIEW.

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.

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.

Conditional microglial depletion in rats leads to reversible anorexia and weight loss by disrupting gustatory circuitry.

Microglia are highly sensitive to dietary influence, becoming activated acutely and long-term by high fat diet. However, their role in regulating satiety and feeding in healthy individuals remains unclear. Here we show that microglia are essential for the normal regulation of satiety and metabolism in rats. Short-term microglial depletion in a Cx3cr1-Dtr rat led to a dramatic weight loss that was largely accounted for by an acute reduction in food intake. This weight loss and anorexia were not likely due to a sickness response since the rats did not display peripheral or central inflammation, withdrawal, anxiety-like behavior, or nausea-associated pica. Hormonal and hypothalamic anatomical changes were largely compensatory to the suppressed food intake, which occurred in association with disruption of the gustatory circuitry at the paraventricular nucleus of the thalamus. Thus, microglia are important in supporting normal feeding behaviors and weight, and regulating preference for palatable food. Inhibiting this circuitry is able to over-ride strong compensatory drives to eat, providing a potential target for satiety control.

Homeostatic circuits selectively gate food cue responses in insular cortex.

Physiological needs bias perception and attention to relevant sensory cues. This process is 'hijacked' by drug addiction, causing cue-induced cravings and relapse. Similarly, its dysregulation contributes to failed diets, obesity, and eating disorders. Neuroimaging studies in humans have implicated insular cortex in these phenomena. However, it remains unclear how 'cognitive' cortical representations of motivationally relevant cues are biased by subcortical circuits that drive specific motivational states. Here we develop a microprism-based cellular imaging approach to monitor visual cue responses in the insular cortex of behaving mice across hunger states. Insular cortex neurons demonstrate food-cue-biased responses that are abolished during satiety. Unexpectedly, while multiple satiety-related visceral signals converge in insular cortex, chemogenetic activation of hypothalamic 'hunger neurons' (expressing agouti-related peptide (AgRP)) bypasses these signals to restore hunger-like response patterns in insular cortex. Circuit mapping and pathway-specific manipulations uncover a pathway from AgRP neurons to insular cortex via the paraventricular thalamus and basolateral amygdala. These results reveal a neural basis for state-specific biased processing of motivationally relevant cues.

Central and peripheral control of food intake.

The maintenance of the body weight at a stable level is a major determinant in keeping the higher animals and mammals survive. Th e body weight depends on the balance between the energy intake and energy expenditure. Increased food intake over the energy expenditure of prolonged time period results in an obesity. Th e obesity has become an important worldwide health problem, even at low levels. The obesity has an evil effect on the health and is associated with a shorter life expectancy. A complex of central and peripheral physiological signals is involved in the control of the food intake. Centrally, the food intake is controlled by the hypothalamus, the brainstem, and endocannabinoids and peripherally by the satiety and adiposity signals. Comprehension of the signals that control food intake and energy balance may open a new therapeutic approaches directed against the obesity and its associated complications, as is the insulin resistance and others. In conclusion, the present review summarizes the current knowledge about the complex system of the peripheral and central regulatory mechanisms of food intake and their potential therapeutic implications in the treatment of obesity.

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.

Satiety Impact of Different Potato Products Compared to Pasta Control.

OBJECTIVE: A variety of potato dishes are regularly consumed worldwide, but the satiety value of these foods is not well established. The primary objective of this study was to compare the satiating effects of 4 equi-energy meals containing different potato preparations with an equi-energy pasta control meal. METHODS: This study used a randomized crossover design to assess the impact of 4 equi-energy potato-based meals (fried French fries, baked potato, mashed potato, or potato wedges) on subjective satiety sensations (visual analogue scale [VAS] ratings) and subsequent energy intake (ad libitum meal [kcal]), compared to a control pasta-based meal. Thirty-three healthy nonobese men and women participated in the study. RESULTS: VAS ratings indicated that the meal containing fried french fries was perceived to be substantially more satiating than the equi-energy pasta control meal, with all other potato-based meals not differing overall from control. All test meals had a comparable effect on energy intake at a later ad libitum meal. CONCLUSIONS: Consumers reported higher levels of satiety following a meal where the principal carbohydrate source was fried french fries, compared to when they had consumed an energy-matched meal containing carbohydrate in the form of pasta. All other potato preparations had similar effects on satiety as pasta. It is concluded that participants perceived a meal with fried french fries as providing greater satiety than a pasta control meal.

Formulación de barras nutricionales con proteínas lácteas: índice glucémico y efecto de saciedad / Formulation of nutritional bars with dairy proteins: glycemic index and satiety effect

Se ha estudiado el índice glicémico, la carga glicémica y el efecto de saciedad producido en adultos jóvenes (12 hombres y 8 mujeres) por el consumo de tres tipos de barritas nutricionales formuladas con proteínas lactoséricas (LS), caseínas (CS) o hidratos de carbono (HC) frente a un control (C). Los valores de glucemia en la sangre a los 30 min fueron significativamente mayores (p < 0,05) para la barra HC (129 ± 8 mg/dl) frente a las barras CS (103 ± 6 mg/dl) y LS (86 ± 8 mg/dl). Asimismo, también se encontraron diferencias estadísticamente significativas (p < 0,05) entre los índices glicémicos de los tres tipos de barras estudiadas (LS = 11,5 ± 3,9; CS = 40,7 ± 6,5; HC = 68,8 ± 13,0). Por otro lado, las barritas nutricionales formuladas con proteínas lácteas (LS y CS) muestran un efecto de saciedad mucho más intenso y prolongado que la formulada con hidratos de carbono (HC), lo que pone de manifiesto el potencial de estas proteínas para ser utilizadas en la formulación de productos para diabéticos y dietéticos (AU)

It has been studied in young adults (12 men and 8 women) the glycemic index, glycemic load and satiety effect produced by three types of nutritional bars formulated with whey proteins (LS), caseins (CS) or carbohydrates (HC) against a control group (C). It has been found significant differences (p < 0.05) in relation to blood sugar levels for HC bar (129 ± 8 mg/dl) against CS bar (103 ± 6 mg/dl) and LS bar (86 ± 8 mg/dl) after 30 min of its intake. Furthermore, it has also been found significant differences (p < 0.05) between glycemic index of three types of studied bars (LS = 11.5 ± 3.9; CS = 40.7 ± 6.5; HC = 68.8 ± 13.0). On the other hand, nutritional bars formulated with dairy proteins (LS y CS) showed a satiety effect more heavy and prolonged than carbohydrate bar (HC). The results reveal that dairy proteins may be used as functional ingredients to develop diabetic and dietary supplies (AU)

Elucidation of the anatomy of a satiety network: Focus on connectivity of the parabrachial nucleus in the adult rat.

We hypothesized that brain regions showing neuronal activation after refeeding comprise major nodes in a satiety network, and tested this hypothesis with two sets of experiments. Detailed c-Fos mapping comparing fasted and refed rats was performed to identify candidate nodes of the satiety network. In addition to well-known feeding-related brain regions such as the arcuate, dorsomedial, and paraventricular hypothalamic nuclei, lateral hypothalamic area, parabrachial nucleus (PB), nucleus of the solitary tract and central amygdalar nucleus, other refeeding activated regions were also identified, such as the parastrial and parasubthalamic nuclei. To begin to understand the connectivity of the satiety network, the interconnectivity of PB with other refeeding-activated neuronal groups was studied following administration of anterograde or retrograde tracers into the PB. After allowing for tracer transport time, the animals were fasted and then refed before sacrifice. Refeeding-activated neurons that project to the PB were found in the agranular insular area; bed nuclei of terminal stria; anterior hypothalamic area; arcuate, paraventricular, and dorsomedial hypothalamic nuclei; lateral hypothalamic area; parasubthalamic nucleus; central amygdalar nucleus; area postrema; and nucleus of the solitary tract. Axons originating from the PB were observed to closely associate with refeeding-activated neurons in the agranular insular area; bed nuclei of terminal stria; anterior hypothalamus; paraventricular, arcuate, and dorsomedial hypothalamic nuclei; lateral hypothalamic area; central amygdalar nucleus; parasubthalamic nucleus; ventral posterior thalamic nucleus; area postrema; and nucleus of the solitary tract. These data indicate that the PB has bidirectional connections with most refeeding-activated neuronal groups, suggesting that short-loop feedback circuits exist in this satiety network. J. Comp. Neurol. 524:2803-2827, 2016. © 2016 Wiley Periodicals, Inc.

The effects of potatoes and other carbohydrate side dishes consumed with meat on food intake, glycemia and satiety response in children.

BACKGROUND: The effect of carbohydrate (CHO) foods on blood glucose (BG) is ranked by their glycemic index (GI). Boiled and mashed potatoes (BMPs) are ranked as high GI foods, whereas pasta and rice have moderate GI rankings. The objective of this study was to compare ad libitum consumption of common CHO dishes consumed with meat on meal-time food intake and post-meal satiety, BG, insulin and gut hormones in 11- to 13-year-old normal weight children. METHODS: Two randomized crossover studies were conducted. At weekly intervals, children (experiment 1: 12 males (M), 8 females (F); experiment 2: 6M, 6 F) received in random order 1 of 5 CHO side dishes of rice, pasta, BMP, fried French fries (FFF) or baked French fries (BFF) eaten freely together with a fixed amount of lean beef (100 g). In experiment-1, food intake over 30 min and subjective appetite were measured for 120 min. In experiment-2, the same outcomes were measured along with BG, plasma insulin and gut hormones. RESULTS: The results for boys and girls were pooled as sex was not a factor. In both experiments, children consumed 30-40% less calories at meals with BMP (P<0.0001) compared with all other treatments, which were similar. BMP increased satiety, expressed as a change in appetite per kilocalorie, more than all other treatments (P<0.0001). FFF resulted in the lowest (P<0.0001) glucose and insulin at meal end and post-meal and peptide YY (PYY) post-meal. Blood measures were similar among all other treatments. CONCLUSIONS: The physiological functions of CHO foods consumed ad libitum at meal time on food intake, appetite, BG, insulin and gut hormone responses in children is not predicted by the GI.

Brain dynamics of meal size selection in humans.

Although neuroimaging research has evidenced specific responses to visual food stimuli based on their nutritional quality (e.g., energy density, fat content), brain processes underlying portion size selection remain largely unexplored. We identified spatio-temporal brain dynamics in response to meal images varying in portion size during a task of ideal portion selection for prospective lunch intake and expected satiety. Brain responses to meal portions judged by the participants as 'too small', 'ideal' and 'too big' were measured by means of electro-encephalographic (EEG) recordings in 21 normal-weight women. During an early stage of meal viewing (105-145 ms), data showed an incremental increase of the head-surface global electric field strength (quantified via global field power; GFP) as portion judgments ranged from 'too small' to 'too big'. Estimations of neural source activity revealed that brain regions underlying this effect were located in the insula, middle frontal gyrus and middle temporal gyrus, and are similar to those reported in previous studies investigating responses to changes in food nutritional content. In contrast, during a later stage (230-270 ms), GFP was maximal for the 'ideal' relative to the 'non-ideal' portion sizes. Greater neural source activity to 'ideal' vs. 'non-ideal' portion sizes was observed in the inferior parietal lobule, superior temporal gyrus and mid-posterior cingulate gyrus. Collectively, our results provide evidence that several brain regions involved in attention and adaptive behavior track 'ideal' meal portion sizes as early as 230 ms during visual encounter. That is, responses do not show an increase paralleling the amount of food viewed (and, in extension, the amount of reward), but are shaped by regulatory mechanisms.

[Glucose homeostasis and gut-brain connection]. / Contrôle de la glycémie par l'axe nerveux intestin-cerveau.

Since the XIX(th) century, the brain has been known for its role in regulating food intake (via the control of hunger sensation) and glucose homeostasis. Further interest has come from the discovery of gut hormones, which established a clear link between the gut and the brain in regulating glucose and energy homeostasis. The brain has two particular structures, the hypothalamus and the brainstem, which are sensitive to information coming either from peripheral organs or from the gut (via circulating hormones or nutrients) about the nutritional status of the organism. However, the efforts for a better understanding of these mechanisms have allowed to unveil a new gut-brain neural axis as a key regulator of the metabolic status of the organism. Certain nutrients control the hypothalamic homeostatic function via this axis. In this review, we describe how the gut is connected to the brain via different neural pathways, and how the interplay between these two organs drives the energy balance.

Hypothalamic gene expression underlying pre-hibernation satiety.

Prior to hibernation, 13-lined ground squirrels (Ictidomys tridecemlineatus) enter a hypophagic period where food consumption drops by an average of 55% in 3 weeks. This occurs naturally, while the ground squirrels are in constant environmental conditions and have free access to food. Importantly, this transition occurs before exposure to hibernation conditions (5°C and constant darkness), so the ground squirrels are still maintaining a moderate level of activity. In this study, we used the Illumina HiSeq 2000 system to sequence the hypothalamic transcriptomes of ground squirrels before and after the autumn feeding transition to examine the genes underlying this extreme change in feeding behavior. The hypothalamus was chosen because it is known to play a role in the control and regulation of food intake and satiety. Overall, our analysis identified 143 genes that are significantly differentially expressed between the two groups. Specifically, we found five genes associated with feeding behavior and obesity (VGF, TRH, LEPR, ADIPOR2, IRS2) that are all upregulated during the hypophagic period, after the feeding transition has occurred. We also found that serum leptin significantly increases in the hypophagic group. Several of the genes associated with the natural autumnal feeding decline in 13-lined ground squirrels show parallels to signaling pathways known to be disrupted in human metabolic diseases, like obesity and diabetes. In addition, many other genes were identified that could be important for the control of food consumption in other animals, including humans.

Hypothalamic POMC neurons promote cannabinoid-induced feeding.

Hypothalamic pro-opiomelanocortin (POMC) neurons promote satiety. Cannabinoid receptor 1 (CB1R) is critical for the central regulation of food intake. Here we test whether CB1R-controlled feeding in sated mice is paralleled by decreased activity of POMC neurons. We show that chemical promotion of CB1R activity increases feeding, and notably, CB1R activation also promotes neuronal activity of POMC cells. This paradoxical increase in POMC activity was crucial for CB1R-induced feeding, because designer-receptors-exclusively-activated-by-designer-drugs (DREADD)-mediated inhibition of POMC neurons diminishes, whereas DREADD-mediated activation of POMC neurons enhances CB1R-driven feeding. The Pomc gene encodes both the anorexigenic peptide α-melanocyte-stimulating hormone, and the opioid peptide ß-endorphin. CB1R activation selectively increases ß-endorphin but not α-melanocyte-stimulating hormone release in the hypothalamus, and systemic or hypothalamic administration of the opioid receptor antagonist naloxone blocks acute CB1R-induced feeding. These processes involve mitochondrial adaptations that, when blocked, abolish CB1R-induced cellular responses and feeding. Together, these results uncover a previously unsuspected role of POMC neurons in the promotion of feeding by cannabinoids.

Effects of diphenyl and p-chloro-diphenyl diselenides on feeding behavior of rats.

RATIONALE: The searching for safe and effective antiobesity drugs has been the subject of intense research. Previous studies have shown several pharmacological applications of organoselenium compounds; however, their possible anorectic-like actions have not been investigated. OBJECTIVE: This study aims to investigate the effects of (PhSe)2 and (p-ClPhSe)2 on feeding behavior of rats and their potential as weight-reducing agents. METHODS: The effects of intraperitoneal administration of diselenides were investigated through the microstructural pattern of feeding behavior, behavioral satiety sequence (BSS), hypothalamic serotonin (5-HT) uptake, body weight, and epididymal fat content of male rats. RESULTS: Our findings demonstrated that food intake of fasted rats was reduced by both diselenides (1 and 10 mg/kg). Diphenyl diselenide [(PhSe)2] (1 mg/kg) and p-chloro-diphenyl diselenide [(p-ClPhSe)2] (10 mg/kg) decreased the frequency, mean duration, and mean size of meals compared with the control treatment. The BSS structure was preserved when organoselenium compounds (1 mg/kg) were administered, and it was associated to a displacement to the left when the resting period started indicating a satiating action. Inhibition of 5-HT uptake in the hypothalamus (∼20 %) was also found in rats treated with low doses of (PhSe)2 and (p-ClPhSe)2 (1 mg/kg). Treatments with a high dose of both diselenides (10 mg/kg) carried out for 7 days induced weight loss and epididymal fat reduction in sated rats. CONCLUSION: This study suggests that diselenides caused a satiating action in rats that could be partially explained by the inhibition of hypothalamic 5-HT uptake. These organoselenium compounds were potential weight-reducing agents when repeatedly administered.

Timed-daily ingestion of whey protein and exercise training reduces visceral adipose tissue mass and improves insulin resistance: the PRISE study.

The present study examined the effects of timed ingestion of supplemental protein (20-g servings of whey protein, 3×/day), added to the habitual diet of free-living overweight/obese adults and subsequently randomized to either whey protein only (P; n = 24), whey protein and resistance exercise (P + RT; n = 27), or a whey protein and multimode exercise training program [protein and resistance exercise, intervals, stretching/yoga/Pilates, endurance exercise (PRISE); n = 28]. Total and regional body composition and visceral adipose tissue (VAT) mass (dual-energy X-ray absorptiometry), insulin sensitivity [homeostasis model assessment-estimated insulin resistance (HOMA-IR)], plasma lipids and adipokines, and feelings of hunger and satiety (visual analog scales) were measured before and after the 16-wk intervention. All groups lost body weight, fat mass (FM), and abdominal fat; however, PRISE lost significantly (P < 0.01) more body weight (3.3 ± 0.7 vs. 1.1 ± 0.7 kg, P + RT) and FM (2.8 ± 0.7 vs. 0.9 ± 0.5 kg, P + RT) and gained (P < 0.05) a greater percentage of lean body mass (2 ± 0.5 vs. 0.9 ± 0.3 and 0.6 ± 0.4%, P + RT and P, respectively). Only P + RT (0.1 ± 0.04 kg) and PRISE (0.21 ± 0.07 kg) lost VAT mass (P < 0.05). Fasting glucose decreased only in P + RT (5.1 ± 2.5 mg/dl) and PRISE (15.3 ± 2.1 mg/dl), with the greatest decline occurring in PRISE (P < 0.05). Similarly, HOMA-IR improved (0.6 ± 0.3, 0.6 ± 0.4 units), and leptin decreased (4.7 ± 2.2, 4.7 ± 3.1 ng/dl), and adiponectin increased (3.8 ± 1.1, 2.4 ± 1.1 µg/ml) only in P + RT and PRISE, respectively, with no change in P. In conclusion, we find evidence to support exercise training and timed ingestion of whey protein added to the habitual diet of free-living overweight/obese adults, independent of caloric restriction on total and regional body fat distribution, insulin resistance, and adipokines.