Bariatric endoscopy: Keep it simple and smart

Calorie Restriction in the Elderly People

Hypothalamic Control of Food Intake and Energy Homeostasis

Background & AimsLeptin, the protein product of the ob gene, increases energy expenditure and reduces food intake, thereby promoting weight reduction. Leptin also regulates glucose homeostasis and hepatic insulin sensitivity via hypothalamic proopiomelanocortin neurons in mice. Roux-en-Y gastric bypass (RYGB) induces weight loss that is substantial and sustained despite reducing plasma leptin levels. In addition, patients who fail to undergo diabetes remission after RYGB are hypoletinemic compared to those who do and to lean controls. We have previously demonstrated that the beneficial effects of RYGB in mice require the melanocortin-4 receptor, a downstream effector of leptin action. Based on these observations, we hypothesized that leptin is required for sustained weight reduction and improved glucose homeostasis observed after RYGB.MethodsTo investigate this hypothesis, we performed RYGB or sham operations on leptin-deficient ob/ob mice maintained on regular chow. To investigate whether leptin is involved in post-RYGB weight maintenance, we challenged post-surgical mice with high fat diet.ResultsRYGB reduced total body weight, fat and lean mass and caused reduction in calorie intake in ob/ob mice. However, it failed to improve glucose tolerance, glucose-stimulated plasma insulin, insulin tolerance, and fasting plasma insulin. High fat diet eliminated the reduction in calorie intake observed after RYGB in ob/ob mice and promoted weight regain, although not to the same extent as in sham-operated mice. We conclude that leptin is required for the effects of RYGB on glucose homeostasis but not body weight or composition in mice. Our data also suggest that leptin may play a role in post-RYGB weight maintenance.

besity is one of the most serious problems of public health and the fifth leading cause of death. It is estimated that 44% of diabetic load, 23% of heart ischemic load and 7-41% of all cancers load are related to obesity. Approximately 80% of older adults (+65years) have at least one of the above mentioned chronic diseases, and 50% have at least two chronic disease (1). Along with other organs, brain is also affected with aging and high calorie intake as Fitzpatrik and colleagues suggested in a review article that obese people have problems on decision-making, planning and solving skill, with fewer difficulties on the tasks of verbal fluency, learning and memory (2). In contrast, a reduction of calorie intake without malnutrition called “calorie restriction” (CR) has a wide range of benefits. Moderate CR can prevent or reverse the damaging effects of overweight/obesity, type 2 diabetes, hypertension, chronic inflammation and other age-associated metabolic diseases (1). As the first groups who worked on CR, Osborne et al. in 1917 showed that reducing calorie intake in rats increased their length of life. Since then, large amount of time and research efforts have been and continued to be devoted to the study of anti-aging and anti-cancer mechanisms underlying CR in yeasts, worms, insects, rodents and humans (3). Significant increase in life span has been reported when the nutrient availability drops between 30% and 75% of normal calorie provision, according to the species. Not only calorie restricted rodents lived longer than the adlibitum-fed counterparts but a significant part of them (about 30%) died without any apparent pathology, raising the striking possibility that aging is not necessarily tightly linked with costly pathologies (4). Preliminary results from human studies are reproducing many of the metabolic and physiological responses sobserved in rodents and monkeys. Short term CR (6-24 months) induces reduction of body weight, subcutaneous and visceral fat, lean body mass, insulin, energy expenditure, and core body temperature (5). Core body temperature, levels of dehydro-epiandrosterone sulfate (DHEAS) and insulin are biomarkers of CR and longevity in human similar to rodents and monkeys. In a 6-month CR related study on overweight individuals, a significant reduction of fasting insulin levels and core body temperature in CR and CR with exercise group has been reported; however, DHEAS and fasting glucose remained unchanged, as DHEAS falls 2-4% per year in humans. The other hypothesis to explain the antiaging effects of CR is reduced energy expenditure with a consequent reduction in the production of reactive oxygen species (ROS). In this study, a metabolic adaptation over 24 hours following 6 months of CR has also occurred (6). CR decreases serum insulin-like growth factor1 (IGF-1) concentration by approximately 40% in rodents. This is a key role in protection against cancer and slowing age; as IGF-1 promotes tumor development and inhibits apoptosis (3). Cognitive impairment and calorie restriction Evidence from clinical and basic researches points to a deep connection between brain function decline and metabolic dysregulation during senescence. Excess nutrient availability may be detrimental to brain function. Conversely, a 30% reduction in O

Childhood obesity: a hefty challenge

The Quantity of Meal Fat Influences the Profile of Postprandial Hormones as Well as Hunger Sensation in Healthy Elderly People

We are writing in regards to the original article “Randomized Clinical Trial of Portion-Controlled Prepackaged Foods to Promote Weight Loss” authored by Rock et al. (1). Since achieving and maintaining a healthy body weight is an important subject of everyday care, we read this article with great interest. We complement Rock et al. on their study design to research whether portion-controlled prepackaged foods promote more weight loss than self-selected diet. The study design enables Rock et al. to measure the true effect from the diet apart from the effects of the other interventions. However, we have some concerns about the study. Our main concern is the effect of differences in participant demographic characteristics between intervention and control groups. The percentage of men and women is skewed between both groups. The intervention group contains a relative higher percentage of men, namely 8.6%. Furthermore, the ethnicity is not equally divided among the groups. There are no participants with an Asian American ethnicity in the control group, whereas 9.5% of the participants in the intervention group are of Asian American ethnicity. These skewed characteristics may partly explain the measured significant difference of weight loss at 3 months in the intervention group. In our opinion, the authors should have investigated at least if correction for this skewed distribution was necessary. However, the authors did not mention anything about correction. Another point we would like to discuss is the argument that the weight loss achieved in this study of 3 months is relevant for long-term success. The references ( (2-4)) used to support this argument described initial weight loss as a predictor of long-term weight loss, but they achieved this with a longer intervention period of 1 to 2 years and showed that final weight loss was about half the weight loss achieved after 9 months of intervention. In short, it cannot be concluded in our opinion that the obtained weight loss will be likely to last, since this intervention was conducted for only 3 months. Although the description of the measurements and instruments was detailed, there was no information about how weight measurements were conducted. Since this was the primary outcome of this study, we expected detailed information about the protocol for weight measurements and the used instrument. In our opinion, the monitoring of the accuracy and the precision of the scale should be mentioned. Finally, it seems that the advised reduction in caloric intake by the dietician took place after randomization. It is unclear whether the advised reduction in caloric intake is equal in both control and intervention groups. In conclusion, Rock et al. have completed a detailed trial that covered all the basics, like dietitian, weekly behavioral weight loss guidance, and usage of applications to monitor and guide diet and exercise. This resulted in a high percentage of weight loss. The used design is very helpful for further trials on achieving a healthy weight. However, the above-mentioned questions remain. We are looking forward to hearing from the authors.

Resveratrol, a polyphenol compound, is known for its effects on energy homeostasis. With properties of energy sensors mediating effects of calorie restriction, sirtuins are targets of resveratrol. The mammalian sirtuin homolog SIRT1 is a protein deacetylase playing a role in glucose metabolism and islet function. Here, we investigated the effects of resveratrol and possible link with SIRT1 in β-cells. Insulinoma INS-1E cells and human islets were cultured with resveratrol before analyzing their physiological responses. Treatment of INS-1E cells for 24 h with 25 μM resveratrol resulted in marked potentiation of glucose-stimulated insulin secretion. This effect was associated with elevated glycolytic flux, resulting in increased glucose oxidation, ATP generation, and mitochondrial oxygen consumption. Such changes correlated with up-regulation of key genes for β-cell function, i.e. Glut2, glucokinase, Pdx-1, Hnf-1α, and Tfam. In human islets, chronic resveratrol treatment similarly increased both the glucose secretory response and expression of the same set of genes, eventually restoring the glucose response in islets obtained from one type 2 diabetic donor. Overexpression of Sirt1 in INS-1E cells potentiated resveratrol effects on insulin secretion. Conversely, inhibition of SIRT1 achieved either by expression of an inactive mutant or by using the EX-527 inhibitor, both abolished resveratrol effects on glucose responses. Treatment of INS-1E cells with EX-527 also prevented resveratrol-induced up-regulation of Glut2, glucokinase, Pdx-1, and Tfam. Resveratrol markedly enhanced the glucose response of INS-1E cells and human islets, even after removal of the compound from the medium. These effects were mediated by and fully dependent on active SIRT1, defining a new role for SIRT1 in the regulation of insulin secretion.

Obesity is a chronic, relapsing, degenerative, multifactorial disease that is associated with many co-morbidities. The global increasing burden of obesity has led to calls for an urgent need for additional treatment options. Given the rapid expansion of bariatric endoscopy and bariatric surgery across Europe, the European Society of Gastrointestinal Endoscopy (ESGE) has recognized the need to formalize and enhance training in bariatric endoscopy and the endoscopic treatment of bariatric surgical adverse events. This manuscript represents the outcome of a formal Delphi process resulting in an official Position Statement of the ESGE and provides a framework to develop and maintain skills in bariatric endoscopy and the endoscopic treatment of bariatric surgical adverse events. This curriculum is set out in terms of the prerequisites prior to training, minimum number of procedures, the steps for training and quality of training, and how competence should be defined and evidenced before independent practice. 1: ESGE recommends that every endoscopist should have achieved competence in upper gastrointestinal endoscopy before commencing training in bariatric endoscopy and the endoscopic treatment of bariatric surgical adverse events. 2: Trainees in bariatric endoscopy and the endoscopic treatment of the complications of bariatric surgery should have basic knowledge of the definition, classification, and social impact of obesity, its pathophysiology, and its related co-morbidities. The recognition and management of gastrointestinal diseases that are more common in patients with obesity, along with participation in multidisciplinary teams where obese patients are evaluated, are mandatory. 3 : ESGE recommends that competency in bariatric endoscopy and the endoscopic treatment of the complications of bariatric surgery can be learned by attending validated training courses on simulators initially, structured training courses, and then hands-on training in tertiary referral centers.

Olfactory inputs are important for hedonic evaluation of food, resulting in food choice and possible consumption. Olfactory acuity is determined by the feeding status, with hunger enhancing smell and food seeking behavior, whereas satiety suppresses olfaction and promotes energy expenditure. Efforts to understand the cellular basis of food intake and energy expenditure revealed the crucial role of the hypothalamus as a master regulator of whole-body energy homeostasis, integrating internal and external stimuli to modulate energy intake and expenditure accordingly. However, how the hypothalamus adjusts circuits regulating energy homeostasis depending on external stimuli, such as smell, remains an intriguing mystery. Our previous work revealed that ablation of olfactory sensory neurons (OSNs) stimulates hypothalamic-driven autonomic tone and promotes catabolic pathways, enhancing thermogenesis in adipose tissue. These findings unravel a new function for the olfactory system in controlling energy homeostasis in response to sensory signals. Here, we analyzed neural circuits connecting olfaction and hypothalamus and determined the role of olfactory inputs on energy homeostasis. To identify neural circuits linking olfactory and hypothalamic neurons, we conducted anterograde viral tracing from mitral cell layer in the main olfactory bulb (MOB) in Tbx21-Cre mice and retrograde viral tracing from pro-opiomelanoctin (POMC)- and agouti-related protein (AgRP)-expressing hypothalamic neurons in POMC-Cre and AgRP-IRES-Cre mice using Cre-dependent helper virus and modified rabies virus. Additionally, we used chemical ablation of mature OSNs and chemogenetic silencing of mitral cell layer neurons to determine the effect of olfaction on energy homeostasis. Our data suggest that piriform cortex (PC)-amygdala (Amy)-arcuate nucleus of hypothalamus (ARC) is one of the plausible circuits responsible for transferring signals from MOB to the hypothalamus. Disclosure C. Riera: None. Funding American Diabetes Association/Pathway to Stop Diabetes (1-15-INI-12)

Hindbrain catecholamine neurons contribute to control of daily food intake during chronic leptin treatment.

Obesity is achronic, progressive, and relapsing disease that can contribute to morbidity, reduced life expectancy, and adverse health outcomes. The prevalence of obesity increased worldwide in the past 60years, mainly because of changes in our environment and society. With the technical revolution of the last century, new modes of transportation and working conditions, automatization, and computerization, human energy demands have decreased. In parallel, the availability of energy-dense food, refined carbohydrates, and fat has markedly increased. These developments in society clash with biological factors that predispose humans to the development of obesity. At the individual level, obesity is the result of along-term imbalance between too much energy consumed and too little energy expended. Therefore, lifestyle and behavior interventions aimed at reducing calorie intake and increasing energy expenditure target the root causes of obesity. However, both at the individual and population level, obesity prevention and treatment strategies that are based only on behavior modification are frequently not successful in the long term. The limited effectiveness of behavior interventions on weight loss are explained by complex and persistent hormonal, metabolic, and neurochemical adaptations that prevent weight loss and promote weight regain. However, behavior interventions lead to important health benefits beyond weight loss and are therefore an integral part of obesity management. This review discusses how abetter understanding of the pathophysiology of obesity can influence weight loss strategies through behavioral modification. The complex factors contributing to the development of obesity require amultimodal long-term approach that is based on behavior interventions but may also include pharmacological or surgical approaches. The treatment paradigm has recently shifted from simple weight loss strategies towards treating obesity as amultisystem disease.

CNS-targets in control of energy and glucose homeostasis

The ion channel TRPV1 is involved in a wide range of processes including nociception, thermosensation and, more recently discovered, energy homeostasis. Tightly controlling energy homeostasis is important to maintain a healthy body weight, or to aid in weight loss by expending more energy than energy intake. TRPV1 may be involved in energy homeostasis, both in the control of food intake and energy expenditure. In the periphery, it is possible that TRPV1 can impact on appetite through control of appetite hormone levels or via modulation of gastrointestinal vagal afferent signaling. Further, TRPV1 may increase energy expenditure via heat production. Dietary supplementation with TRPV1 agonists, such as capsaicin, has yielded conflicting results with some studies indicating a reduction in food intake and increase in energy expenditure, and other studies indicating the converse. Nonetheless, it is increasingly apparent that TRPV1 may be dysregulated in obesity and contributing to the development of this disease. The mechanisms behind this dysregulation are currently unknown but interactions with other systems, such as the endocannabinoid systems, could be altered and therefore play a role in this dysregulation. Further, TRPV1 channels appear to be involved in pancreatic insulin secretion. Therefore, given its plausible involvement in regulation of energy and glucose homeostasis and its dysregulation in obesity, TRPV1 may be a target for weight loss therapy and diabetes. However, further research is required too fully elucidate TRPV1s role in these processes. The review provides an overview of current knowledge in this field and potential areas for development.

Energy homeostasis requires a balance between food intake and energy expenditure. Neurons in the hypothalamus and brainstem detect signals from the gastrointestinal tract, adipose tissue, and other peripheral organs and integrate this information to provide appropriate responses to ensure energy balance. This chapter will examine the central neuronal circuits involved in the control of hunger, satiety, and energy homeostasis. In addition to conveying pertinent information about short- and long-term energy status, the hypothalamus and brainstem provide input to higher cortical and limbic areas involved in voluntary and hedonic control of eating behavior. Understanding these mechanisms will aid the management of obesity and associated metabolic diseases.