The interplay between leptin, glucocorticoids, and GLP1 regulates food intake and feeding behaviour.

Nutritional, endocrine, and neurological signals converge in multiple brain centres to control feeding behaviour and food intake as part of the allostatic regulation of energy balance. Among the several neuroendocrine systems involved, the leptin, glucocorticoid, and glucagon-like peptide 1 (GLP1) systems have been extensively researched. Leptin is at the top hierarchical level since its complete absence is sufficient to trigger severe hyperphagia. Glucocorticoids are key regulators of the energy balance adaptation to stress and their sustained excess leads to excessive adiposity and metabolic perturbations. GLP1 participates in metabolic adaptation to food intake, regulating insulin secretion and satiety by parallel central and peripheral signalling systems. Herein, we review the brain and peripheral targets of these three hormone systems that integrate to regulate food intake, feeding behaviour, and metabolic homeostasis. We examine the functional relationships between leptin, glucocorticoids, and GLP1 at the central and peripheral levels, including the cross-regulation of their circulating levels and their cooperative or antagonistic actions at different brain centres. The pathophysiological roles of these neuroendocrine systems in dysregulated intake are explored in the two extremes of body adiposity - obesity and lipodystrophy - and eating behaviour disorders.

Corrigendum: Impact of short and long exposure to cafeteria diet on food intake and white adipose tissue lipolysis mediated by glucagon-like peptide 1 receptor.

[This corrects the article DOI: 10.3389/fendo.2023.1164047.].

Impact of short and long exposure to cafeteria diet on food intake and white adipose tissue lipolysis mediated by glucagon-like peptide 1 receptor.

Introduction: The modern food environment facilitates excessive calorie intake, a major driver of obesity. Glucagon-like peptide 1 (GLP1) is a neuroendocrine peptide that has been the basis for developing new pharmacotherapies against obesity. The GLP1 receptor (GLP1R) is expressed in central and peripheral tissues, and activation of GLP1R reduces food intake, increases the expression of thermogenic proteins in brown adipose tissue (BAT), and enhances lipolysis in white adipose tissue (WAT). Obesity decreases the efficiency of GLP1R agonists in reducing food intake and body weight. Still, whether palatable food intake before or during the early development of obesity reduces the effects of GLP1R agonists on food intake and adipose tissue metabolism remains undetermined. Further, whether GLP1R expressed in WAT contributes to these effects is unclear. Methods: Food intake, expression of thermogenic BAT proteins, and WAT lipolysis were measured after central or peripheral administration of Exendin-4 (EX4), a GLP1R agonist, to mice under intermittent-short exposure to CAF diet (3 h/d for 8 days) or a longer-continuous exposure to CAF diet (24 h/d for 15 days). Ex-vivo lipolysis was measured after EX4 exposure to WAT samples from mice fed CAF or control diet for 12 weeks. . Results: During intermittent-short exposure to CAF diet (3 h/d for 8 days), third ventricle injection (ICV) and intra-peritoneal administration of EX4 reduced palatable food intake. Yet, during a longer-continuous exposure to CAF diet (24 h/d for 15 days), only ICV EX4 administration reduced food intake and body weight. However, this exposure to CAF diet blocked the increase in uncoupling protein 1 (UCP1) caused by ICV EX4 administration in mice fed control diet. Finally, GLP1R expression in WAT was minimal, and EX4 failed to increase lipolysis ex-vivo in WAT tissue samples from mice fed CAF or control diet for 12 weeks. . Discussion: Exposure to a CAF diet during the early stages of obesity reduces the effects of peripheral and central GLP1R agonists, and WAT does not express a functional GLP1 receptor. These data support that exposure to the obesogenic food environment, without the development or manifestation of obesity, can alter the response to GLP1R agonists. .

Sleep loss in male rats contributes more to weight gain during sleep disruption than stress assessed by corticosterone.

Sleep disruption (SD) promotes stress which may mediate the effect of SD induced by noise on bodyweight gain and food intake. We determined if the change in bodyweight during SD caused by noise was driven by stress (assessed by corticosterone) and whether the effects of noise on SD, stress and bodyweight were specific to the method of SD or a consequence of SD per se. We isolated stress from SD due to noise by exposing rats to noise during the darkphase to test whether darkphase noise stimulated weight gain, stress and food intake. Male Sprague-Dawley rats slept undisturbed, were exposed to noise during both circadian phases (lightphase vs darkphase) and lightphase gentle handling. Bodyweight, food intake, physical activity, vigilance states, and plasma corticosterone were determined. Darkphase noise did not affect vigilance states. Unlike lightphase noise, darkphase noise and lightphase gentle handling did not stimulate weight gain or food intake. Only gentle handling significantly increased corticosterone levels. Noise during the lightphase increasesed weight gain and food intake by causing SD and these effects were not driven by stress as assessed by corticosterone. These results may have significant implications for developing translational models of insomnia-induced obesity in humans.

Efecto de la dieta CAF sobre la capacidad de EX4 de modular la expresión de marcadores proteicos de oxidación de ácidos grasos y termogénesis en músculo de ratones / Effect of the CAF diet on the ability of EX4 to modulate the expression of protein markers of fatty acid oxidation and thermogenesis in mouse muscle

El ambiente obesogénico promueve la obesidad al facilitar el acceso y consumo de una amplia variedad de alimentos palatables altos en calorías. La activación del receptor de GLP1 (GLP1R) reduce la ingesta de alimentos, enlentece el vaciamiento gástrico y promueve un balance energético negativo a través de su acción en distintos órganos como el músculo esquelético, disminuyendo así el peso corporal. La obesidad inducida por dieta alta en grasa disminuye el efecto anorexigénico de la administración sistémica vía intra-peritoneal de EX4 (agonista de GLP1R). Sin embargo, se desconoce si la exposición a un ambiente obesogénico previo a la manifestación de obesidad disminuye los efectos anorexigénicos de EX4 o un posible efecto de EX4 sobre marcadores de oxidación de ácidos grasos y termogénesis en músculo esquelético. El objetivo de esta investigación fue determinar el efecto a corto plazo de la dieta CAF, un modelo del ambiente obesogénico humano, sobre la capacidad de EX4 de reducir la ingesta y modular la expresión de marcadores proteicos de oxidación de ácidos grasos y termogénesis (CPT1 y UCP2) en músculo de ratones. Nuestros datos muestran que una inyección intraperitoneal de EX4 a ratones C57BL/6J alimentados con dieta CAF o dieta control durante 10 días no altera la ingesta calórica total, peso corporal, o la expresión de proteínas marcadoras de los procesos de beta-oxidación y de termogénesis (CPT1 y UCP2). Estos datos sugieren que protocolos alternativos de administración de EX4 son necesarios para observar los efectos fisiológicos de la activación de GLP1R.

The obesogenic environment promotes obesity by facilitating access to and consumption of a wide variety of palatable, high-calorie foods. Activation of the GLP1 receptor (GLP1R) reduces food intake, slows gastric emptying, and promotes a negative energy balance by acting on organs such as skeletal muscle, thus decreasing body weight. Obesity induced by a high-fat diet decreased the anorexigenic effect of intraperitoneal systemic administration of EX4 (GLP1R agonist). However, it is unknown whether exposure to an obesogenic environment before the manifestation of obesity diminishes the anorexigenic effects of EX4 or a possible effect of EX4 on markers of fatty acid oxidation and thermogenesis in skeletal muscle. This investigation aimed to determine the short-term effect of the CAF diet, a model of the human obesogenic environment, on the ability of EX4 to reduce intake and modulate the expression of protein markers of fatty acid oxidation and thermogenesis (CPT1 and UCP2) in mouse muscle. Our data show that intraperitoneal injection of EX4 to C57BL/6J mice fed CAF diet or control diet for ten days does not alter total caloric intake, body weight, or expression of proteins markers of beta-oxidation and thermogenesis processes (CPT1 and UCP2). These data suggest that alternative EX4 administration protocols are necessary to observe the physiological effects of GLP1R activation.

Palmitic acid control of ciliogenesis modulates insulin signaling in hypothalamic neurons through an autophagy-dependent mechanism.

Palmitic acid (PA) is significantly increased in the hypothalamus of mice, when fed chronically with a high-fat diet (HFD). PA impairs insulin signaling in hypothalamic neurons, by a mechanism dependent on autophagy, a process of lysosomal-mediated degradation of cytoplasmic material. In addition, previous work shows a crosstalk between autophagy and the primary cilium (hereafter cilium), an antenna-like structure on the cell surface that acts as a signaling platform for the cell. Ciliopathies, human diseases characterized by cilia dysfunction, manifest, type 2 diabetes, among other features, suggesting a role of the cilium in insulin signaling. Cilium depletion in hypothalamic pro-opiomelanocortin (POMC) neurons triggers obesity and insulin resistance in mice, the same phenotype as mice deficient in autophagy in POMC neurons. Here we investigated the effect of chronic consumption of HFD on cilia; and our results indicate that chronic feeding with HFD reduces the percentage of cilia in hypothalamic POMC neurons. This effect may be due to an increased amount of PA, as treatment with this saturated fatty acid in vitro reduces the percentage of ciliated cells and cilia length in hypothalamic neurons. Importantly, the same effect of cilia depletion was obtained following chemical and genetic inhibition of autophagy, indicating autophagy is required for ciliogenesis. We further demonstrate a role for the cilium in insulin sensitivity, as cilium loss in hypothalamic neuronal cells disrupts insulin signaling and insulin-dependent glucose uptake, an effect that correlates with the ciliary localization of the insulin receptor (IR). Consistently, increased percentage of ciliated hypothalamic neuronal cells promotes insulin signaling, even when cells are exposed to PA. Altogether, our results indicate that, in hypothalamic neurons, impairment of autophagy, either by PA exposure, chemical or genetic manipulation, cause cilia loss that impairs insulin sensitivity.

Integrating the effects of sucrose intake on the brain and white adipose tissue: Could autophagy be a possible link?

Excess dietary sucrose is associated with obesity and metabolic diseases. This relationship is driven by the malfunction of several cell types and tissues critical for the regulation of energy balance, including hypothalamic neurons and white adipose tissue (WAT). However, the mechanisms behind these effects of dietary sucrose are still unclear and might be independent of increased adiposity. Accumulating evidence has indicated that dysregulation of autophagy, a fundamental process for maintenance of cellular homeostasis, alters energy metabolism in hypothalamic neurons and WAT, but whether autophagy could mediate the detrimental effects of dietary sucrose on hypothalamic neurons and WAT that contribute to weight gain is a matter of debate. In this review, we examine the hypothesis that dysregulated autophagy in hypothalamic neurons and WAT is an adiposity-independent effect of sucrose that contributes to increased body weight gain. We propose that excess dietary sucrose leads to autophagy unbalance in hypothalamic neurons and WAT, which increases caloric intake and body weight, favoring the emergence of obesity and metabolic diseases.

Eating contexts determine the efficacy of nutrient warning labels to promote healthy food choices.

Introduction: Unhealthy food choices increase the risk of obesity and its co-morbidities. Nutrition labels are a public health policy that aims to drive individuals toward healthier food choices. Chile has been an example of this policy, where mandatory nutrient warning labels (NWL) identify processed foods high in calories and critical nutrients. Eating contexts influence individual food choices, but whether eating contexts also influence how NWL alter the decision process and selection during food choice is unknown. Methods: In an online mouse-tracking study, participants prompted to health, typical, or unrestricted eating contexts were instructed to choose between pairs of foods in the presence or absence of NWL. Conflict during choices was analyzed using mouse paths and reaction times. Results: NWL increased conflict during unhealthy food choices and reduced conflict during healthy choices in all contexts. However, the probability that NWL reversed an unhealthy choice was 80% in a healthy, 37% in a typical, and 19% in an unrestricted context. A drift-diffusion model analysis showed the effects of NWL on choice were associated with an increased bias toward healthier foods in the healthy and typical but not in the unrestricted context. Discussion: These data suggest that the efficacy of NWL to drive healthy food choices increases in a healthy eating context, whereas NWL are less effective in typical or unrestricted eating contexts.

Impact of Gut and Metabolic Hormones on Feeding Reward.

Ingestion of food activates a cascade of endocrine responses (thereby reflecting a contemporaneous feeding status) that include the release of hormones from the gastrointestinal (GI) tract, such as cholecystokinin (CCK), glucagonlike peptide YY (PYY), peptide PP, and oleoylethanolamide, as well as suppression of ghrelin secretion. The pancreas and adipose tissue, on the other hand, release hormones that serve as a measure of the current metabolic state or the long-term energy stores, that is, insulin, leptin, and adiponectin. It is well known and intuitively understandable that these hormones target either directly (by crossing the blood-brain barrier) or indirectly (e.g., via vagal input) the "homeostatic" brainstem-hypothalamic pathways involved in the regulation of appetite. The current article focuses on yet another target of the metabolic and GI hormones that is critical in inducing changes in food intake, namely, the reward system. We discuss the physiological basis of this functional interaction, its importance in the control of appetite, and the impact that disruption of this crosstalk has on energy intake in select physiological and pathophysiological states. We conclude that metabolic and GI hormones have a capacity to strengthen or weaken a response of the reward system to a given food, and thus, they are fundamental in ensuring that feeding reward is plastic and dependent on the energy status of the organism. © 2021 American Physiological Society. Compr Physiol 11:1425-1447, 2021.

Calcium-Sensing Receptor in Adipose Tissue: Possible Association with Obesity-Related Elevated Autophagy.

Autophagy is upregulated in adipose tissue (AT) from people with obesity. We showed that activation of the calcium-sensing receptor (CaSR) elevates proinflammatory cytokines through autophagy in preadipocytes. Our aim is to understand the role of CaSR on autophagy in AT from humans with obesity. We determined mRNA and protein levels of CaSR and markers of autophagy by qPCR and western blot in human visceral AT explants or isolated primary preadipocytes (60 donors: 72% female, 23-56% body fat). We also investigated their association with donors' anthropometric variables. Donors' % body fat and CaSR mRNA expression in AT were correlated (r = 0.44, p < 0.01). CaSR expression was associated with mRNA levels of the autophagy markers atg5 (r = 0.37, p < 0.01), atg7 (r = 0.29, p < 0.05) and lc3b (r = 0.40, p < 0.01). CaSR activation increased becn and atg7 mRNA expression in AT. CaSR activation also upregulated LC3II by ~50%, an effect abolished by the CaSR inhibitor. Spermine (CaSR agonist) regulates LC3II through the ERK1/2 pathway. Structural equation model analysis suggests a link between donors' AT CaSR expression, AT autophagy and expression of Tumor Necrosis Factor alpha TNF-α. CaSR expression in visceral AT is directly associated with % body fat, and CaSR activation may contribute to obesity-related disruption in AT autophagy.

Palmitic acid reduces the autophagic flux in hypothalamic neurons by impairing autophagosome-lysosome fusion and endolysosomal dynamics.

High-fat diet (HFD)-induced obesity is associated with increased cancer risk. Long-term feeding with HFD increases the concentration of the saturated fatty acid palmitic acid (PA) in the hypothalamus. We previously showed that, in hypothalamic neuronal cells, exposure to PA inhibits the autophagic flux, which is the whole autophagic process from the synthesis of the autophagosomes, up to their lysosomal fusion and degradation. However, the mechanism by which PA impairs autophagy in hypothalamic neurons remains unknown. Here, we show that PA-mediated reduction of the autophagic flux is not caused by lysosomal dysfunction, as PA treatment does not impair lysosomal pH or the activity of cathepsin B.Instead, PA dysregulates autophagy by reducing autophagosome-lysosome fusion, which correlates with the swelling of endolysosomal compartments that show areduction in their dynamics. Finally, because lysosomes undergo constant dynamic regulation by the small Rab7 GTPase, we investigated the effect of PA treatment on its activity. Interestingly, we found PA treatment altered the activity of Rab7. Altogether, these results unveil the cellular process by which PA exposure impairs the autophagic flux. As impaired autophagy in hypothalamic neurons promotes obesity, and balanced autophagy is required to inhibit malignant transformation, this could affect tumor initiation, progression, and/or response to therapy of obesity-related cancers.

Preoperative liking and wanting for sweet beverages as predictors of body weight loss after Roux-en-Y gastric bypass and sleeve gastrectomy.

BACKGROUND/OBJECTIVES: Patients who receive Roux-en-Y gastric bypass (RYGB) lose more weight than those who receive vertical sleeve gastrectomy (VSG). RYGB and VSG alter hedonic responses to sweet flavor, but whether baseline differences in hedonic responses modulate weight loss after RYGB or VSG remains untested. PARTICIPANTS/METHODS: Male and female candidates (n = 66) for RYGB or VSG were recruited and tested for their subjective liking and wanting ratings of sucrose solutions and flavored beverages sweetened with aspartame. Participants were classified by unsupervised hierarchical clustering for their liking and wanting ratings of sucrose and aspartame. Participant liking ratings were also used in a supervised classification using pre-established categories of liking ratings (liker, disliker, and inverted u-shape). Effects of categories obtained from unsupervised or supervised classification on body weight loss and their interaction with surgery type were analyzed separately at 3 and 12 months after surgery using linear models corrected for sex and age. RESULTS: RYGB participants lost more body weight compared with VSG participants at 3 and 12 months after surgery (P < 0.001 for both time points). Unsupervised clustering analysis identified clusters corresponding to high and low wanting or liking ratings for sucrose or aspartame. RYGB participants in high-wanting clusters based on sucrose, but not aspartame, lost more weight than VSG at both 3 (P = 0.01) and 12 months (P = 0.03), yielding a significant cluster by surgery interaction. Categories based on supervised classification using liking ratings for sucrose or aspartame showed no significant effects on body weight loss between RYGB and VSG participants. CONCLUSIONS: Classification of patients into high/low-wanting ratings for sucrose before surgery can predict differential body weight loss after RYGB or VSG in adults and could be used to advise on surgery type.

Noise-induced sleep disruption increases weight gain and decreases energy metabolism in female rats.

BACKGROUND/OBJECTIVES: Inadequate sleep increases obesity and environmental noise contributes to poor sleep. However, women may be more vulnerable to noise and hence more susceptible to sleep disruption-induced weight gain than men. In male rats, exposure to environmental (i.e. ambient) noise disrupts sleep and increases feeding and weight gain. However, the effects of environmental noise on sleep and weight gain in female rats are unknown. Thus, this study was designed to determine whether noise exposure would disturb sleep, increase feeding and weight gain and alter the length of the estrous cycle in female rats. SUBJECTS/METHODS: Female rats (12 weeks old) were exposed to noise for 17d (8 h/d during the light period) to determine the effects of noise on weight gain and food intake. In a separate set of females, estrous cycle phase and length, EEG, EMG, spontaneous physical activity and energy expenditure were recorded continuously for 27d during baseline (control, 9d), noise exposure (8 h/d, 9d) and recovery (9d) from sleep disruption. RESULTS: Noise exposure significantly increased weight gain and food intake compared to females that slept undisturbed. Noise also significantly increased wakefulness, reduced sleep and resulted in rebound sleep during the recovery period. Total energy expenditure was significantly lower during both noise exposure and recovery due to lower energy expenditure during spontaneous physical activity and sleep. Notably, noise did not alter the estrous cycle length. CONCLUSIONS: As previously observed in male rats, noise exposure disrupted sleep and increased weight gain in females but did not alter the length of the estrous cycle. This is the first demonstration of weight gain in female rats during sleep disruption. We conclude that the sleep disruption caused by exposure to environmental noise is a significant tool for determining how sleep loss contributes to obesity in females.

A "NEAT" Approach to Obesity Prevention in the Modern Work Environment.

Increased prevalence of obesity may be due to an increase of being sedentary at work. Increasing non-exercise activity thermogenesis (NEAT) using walking workstations may increase total physical activity and promote a leaner physical body composition (or phenotype). The purpose of this study was to test whether walking slowly during work was sufficient to promote a leaner phenotype by increasing physical activity in sedentary desk workers without inducing compensation or a decrease in activity or energy expenditure during the nonworking hours. We conducted a prospective cohort study using a within-subjects crossover design. The design involved two phases each lasting 2 weeks: a treadmill exercise phase in which subjects used a walking workstation for 2.5 hours a day 5 days/week and a control phase in which subjects maintained their normal work activity. Twenty-five sedentary adults working at the Minneapolis VA Health Care System. We measured body weight, body composition, food intake, 24-hour physical activity, and self-reported physical activity with the International Physical Activity Questionnaire (IPAQ). Treadmill exercise caused a leaner phenotype (lean mass gain and fat mass loss) and significantly increased their 24-hour physical activity. Walking workstation use had favorable effects on physical well-being and mental focus and did not adversely affect productivity. Light treadmill exercise during work can increase physical activity and result in a leaner body composition. This is a potentially useful intervention to increase NEAT in the modern sedentary work environment.

[Eating behavior and its association with nutritional status and physical activity in a general Chilean population]. / Comportamiento hacia los alimentos y su asociación con el estado nutricional y la actividad física en una población general chilena.

INTRODUCTION: obesity has become a chronic disease whose etiology can be based on an imbalance between the contribution and energy expenditure of the individual, where the behavior against food consumption and physical activity play an important role as determinants in this energy balance. METHODS: in the present study, behavior in relation to food consumption and physical activity and its association with nutritional status in a general Chilean population was analyzed. It was a cross-sectional study in 629 people, belonging to the university community of the Andres Bello University. The subjects answered online surveys about sociodemographic, anthropometric, attitude to food consumption (TFEQ) and physical activity (GPAQ). RESULTS: the factorial structure of the TFEQ questionnaire in Spanish showed two factors: the "cognitive restriction" factor and the "disinhibition versus food" factor. With regard to nutritional status, it was found that 39.4% of the population had malnutrition due to excess. In relation to physical activity, half of the subjects performed less than 36 minutes of exercise per day. Individuals with uninhibited behavior towards food presented less practice of total physical activity. Additionally, subjects with low BMI and with greater age were more likely to present a restrictive behavior towards food. CONCLUSION: in the TFEQ questionnaire, two factors were found that explain the variation of behavior in relation to food consumption, which were associated with BMI and with physical activity in the study population.

INTRODUCCIÓN: la obesidad se ha transformado en una enfermedad crónica cuya etiología puede basarse en un desequilibrio entre el aporte y el gasto energético del individuo. Por lo tanto, el comportamiento frente al consumo de alimentos y la actividad física juegan un papel importante como determinantes clave en el resultado del balance energético. MÉTODOS: en el presente estudio se analizó la conducta frente al consumo de alimentos y la actividad física y su asociación con el estado nutricional en una población general chilena. Fue un estudio de corte transversal en 629 personas, pertenecientes a la comunidad universitaria de la Universidad Andres Bello. Los sujetos contestaron encuestas en línea acerca de antecedentes sociodemográficos, antropométricos, actitud frente al consumo de alimentos (TFEQ) y actividad física (GPAQ). RESULTADOS: la estructura factorial del cuestionario TFEQ en español mostró dos factores: el factor de ­restricción cognitiva­ y el factor de ­desinhibición frente a los alimentos­. Con relación al estado nutricional, se encontró que un 39,4% de la población presentó malnutrición por exceso. En cuanto a la actividad física, la mitad de los sujetos realizaban menos de 36 minutos de ejercicio al día. Los individuos con una conducta desinhibida frente a los alimentos presentaron menor práctica de actividad física total. Adicionalmente, sujetos con índice de masa corporal (IMC) bajo y con mayor edad tuvieron mayor probabilidad de presentar una conducta restrictiva frente a los alimentos. CONCLUSIÓN: en el cuestionario TFEQ se encontraron dos factores que explican la variación de la conducta frente al consumo de alimentos, los cuales se asociaron con IMC y con actividad física en la población de estudio.

Comportamiento hacia los alimentos y su asociación con el estado nutricional y la actividad física en una población general chilena / Eating behavior and its association with nutritional status and physical activity in a general Chilean population

Introducción: la obesidad se ha transformado en una enfermedad crónica cuya etiología puede basarse en un desequilibrio entre el aporte y el gasto energético del individuo. Por lo tanto, el comportamiento frente al consumo de alimentos y la actividad física juegan un papel importante como determinantes clave en el resultado del balance energético. Métodos: en el presente estudio se analizó la conducta frente al consumo de alimentos y la actividad física y su asociación con el estado nutricional en una población general chilena. Fue un estudio de corte transversal en 629 personas, pertenecientes a la comunidad universitaria de la Universidad Andres Bello. Los sujetos contestaron encuestas en línea acerca de antecedentes sociodemográficos, antropométricos, actitud frente al consumo de alimentos (TFEQ) y actividad física (GPAQ). Resultados: la estructura factorial del cuestionario TFEQ en español mostró dos factores: el factor de -restricción cognitiva- y el factor de -desinhibición frente a los alimentos-. Con relación al estado nutricional, se encontró que un 39,4% de la población presentó malnutrición por exceso. En cuanto a la actividad física, la mitad de los sujetos realizaban menos de 36 minutos de ejercicio al día. Los individuos con una conducta desinhibida frente a los alimentos presentaron menor práctica de actividad física total. Adicionalmente, sujetos con índice de masa corporal (IMC) bajo y con mayor edad tuvieron mayor probabilidad de presentar una conducta restrictiva frente a los alimentos. Conclusión: en el cuestionario TFEQ se encontraron dos factores que explican la variación de la conducta frente al consumo de alimentos, los cuales se asociaron con IMC y con actividad física en la población de estudio

Introduction: obesity has become a chronic disease whose etiology can be based on an imbalance between the contribution and energy expenditure of the individual, where the behavior against food consumption and physical activity play an important role as determinants in this energy balance. Methods: in the present study, behavior in relation to food consumption and physical activity and its association with nutritional status in a general Chilean population was analyzed. It was a cross-sectional study in 629 people, belonging to the university community of the Andres Bello University. The subjects answered online surveys about sociodemographic, anthropometric, attitude to food consumption (TFEQ) and physical activity (GPAQ). Results: the factorial structure of the TFEQ questionnaire in Spanish showed two factors: the "cognitive restriction" factor and the "disinhibition versus food" factor. With regard to nutritional status, it was found that 39.4% of the population had malnutrition due to excess. In relation to physical activity, half of the subjects performed less than 36 minutes of exercise per day. Individuals with uninhibited behavior towards food presented less practice of total physical activity. Additionally, subjects with low BMI and with greater age were more likely to present a restrictive behavior towards food. Conclusion: in the TFEQ questionnaire, two factors were found that explain the variation of behavior in relation to food consumption, which were associated with BMI and with physical activity in the study population

Updates on the neurobiology of food reward and their relation to the obesogenic environment.

PURPOSE OF REVIEW: To summarize recent findings about the neurobiological control of food reward and discuss their relevance for hedonic food intake and obesity in our current obesogenic environment. RECENT FINDINGS: Recent data show new roles for circuits involving neuronal subpopulations within the central amyglada (CeA) and lateral hypothalamus in the regulation of feeding and reward in rodents under free and operant conditions and also in restrain from reward consumption. Recent work also shows that the orbitofrontal cortex (OFC) codes for subjective perception of food features during reward assessment of individual foods and that activity in the nucleus accumbens (NAc) codes for anticipation for reward, which can be blocked by time-locked neurostimulation of NAc. SUMMARY: New data illustrates that different aspects of hedonic intake and food reward are coded in a distributed brain network. In particular, as our obesogenic environment facilitates access to palatable food and promotes cue-induced feeding, neuronal circuits related to control of impulsivity, food valuation and duration of hedonic intake episodes might have a significant role in our ability to control food intake and development of obesity by excess intake.

Preventive Leptin Administration Protects Against Sepsis Through Improving Hypotension, Tachycardia, Oxidative Stress Burst, Multiple Organ Dysfunction, and Increasing Survival.

Sepsis syndrome is the most important cause of mortality in critically ill patients admitted to intensive care units (ICUs). However, current therapies for its prevention and treatment are still unsatisfactory, and the mortality rate is still high. Non-septic ICU patients are vulnerable to acquire sepsis syndrome. Thus, a preventive treatment for this population is needed. During sepsis syndrome and endotoxemia, severe hypotension, tachycardia, oxidative and immune response increase, multiple organ dysfunction syndrome (MODS) and decreased survival are observed. Leptin administration protects against negative effects of sepsis syndrome and endotoxemia. Furthermore, it is has been reported that leptin elevates blood pressure mediated by sympathetic nervous system activation. However, whether leptin administration before sepsis induction mediates its protective effects during sepsis through blood pressure regulation is not known. Therefore, we investigated whether pre-treatment of leptin improves blood pressure and MODS, resulting in survival increase during endotoxemia. The results showed that leptin administration before endotoxemia induction reduced both the hypotension and tachycardia characteristically observed during endotoxemia. Notably, this protective effect was observed early and late in the course of endotoxemia. Endotoxemia-induced MODS decreased in leptin-treated rats, which was reflected in normal values for liver and kidney function, inhibition of muscle mass wasting and maintenance of glycemia. Furthermore, leptin pre-treatment decreased the oxidative stress burst in blood and blunted the increased pro-inflammatory cytokines TNF-α, IL-1ß, and IL-6 observed during endotoxemia. Remarkably, according to the leptin-induced increase in survival, leptin pre-administration decreased the risk for death associated with sepsis syndrome at early and late times after endotoxemia induction. These results show a potential preventive therapy against sepsis syndrome and endotoxemia in vulnerable patients, based in the beneficial actions of leptin.

Role of Sex and the Environment in Moderating Weight Gain Due to Inadequate Sleep.

PURPOSE OF REVIEW: The growing prevalence of obesity, inadequate sleep and sleep disorders together with the negative impact of lack of sleep on overall health highlights the need for therapies targeted towards weight gain due to sleep loss. RECENT FINDINGS: Sex disparities in obesity and sleep disorders are present; yet, the role of sex is inadequately addressed and thus it is unclear whether sensitivity to sleep disruption differs between men and women. Like sex, environmental factors contribute to the development of obesity and poor sleep. The obesogenic environment is characterized by easy access to palatable foods and a low demand for energy expenditure in daily activities. These and other environmental factors are discussed, as they drive altered sleep or their interaction with food choice and intake can promote obesity. We discuss data that suggest differences in sleep patterns and responses to sleep disruption influence sex disparities in weight gain, and that enviromental disturbances alter sleep and interact with features of the obesogenic environment that together promote obesity.

The Food Environment, Preference, and Experience Modulate the Effects of Exendin-4 on Food Intake and Reward.

OBJECTIVE: The obesogenic food environment facilitates access to multiple palatable foods. Exendin-4 (EX4) is a glucagon-like peptide 1 receptor (GLP1R) agonist that inhibits food intake and has been proposed as an obesity therapy. This study tested whether the composition of the food environment and experience with palatable foods modulate the effects of EX4 on food intake and reward. METHODS: Mice fed a cafeteria (CAF) or control diet were tested for the anorectic effects of EX4 when simultaneously offered foods of varying individual preference and in a conditioned place preference (CPP) test for chocolate. Plasma glucagon-like peptide 1 (GLP1) and hypothalamic GLP1R mRNA were analyzed post mortem. RESULTS: Mice fed a CAF diet developed individual food preference patterns. Offering mice either novel or highly preferred foods decreased the potency of EX4 to inhibit food intake compared to low preference foods or chow. Compared to the control diet, CAF diet intake blocked the decrease in chocolate CPP caused by EX4 and decreased the expression of hypothalamic GLP1R mRNA without altering the plasma GLP1 concentration. CONCLUSIONS: The composition of the food environment, food preference, and experience modulate the ability of EX4 to inhibit food intake and reward. These data highlight the significance of modeling the complexity of the human food environment in preclinical obesity studies.