Obesity, body weight regulation and the brain: Insights from fMRI

Obesity constitutes a major global health threat. Despite the success of bariatric surgery in delivering sustainable weight loss and improvement in obesity-related morbidity, effective non-surgical treatments are urgently needed, necessitating an increased understanding of body weight regulation. Neuroimaging studies undertaken in people with healthy weight, overweight, obesity and following bariatric surgery have contributed to identifying the neurophysiological changes seen in obesity and are increasing our understanding of the mechanisms driving the favourable eating behaviour changes and sustained weight loss engendered by bariatric surgery. These studies have revealed a key interplay between peripheral metabolic signals, homeostatic and hedonic brain regions and genetics. Findings from brain functional magnetic resonance imaging (fMRI) studies have consistently associated obesity with an increased motivational drive to eat, increased reward responses to food cues and impaired food-related self-control processes. Interestingly, new data link these obesity-associated changes with structural and connectivity changes within the central nervous system. Moreover, emerging data suggest that bariatric surgery leads to neuroplastic recovery. A greater understanding of the interactions between peripheral signals of energy balance, the neural substrates that regulate eating behaviour, the environment and genetics will be key for the development of novel therapeutic strategies for obesity. This review provides an overview of our current understanding of the pathoaetiology of obesity with a focus upon the role that fMRI studies have played in enhancing our understanding of central regulation of eating behaviour and energy homeostasis

Reported appetite, taste and smell changes following Roux-en-Y gastric bypass and sleeve gastrectomy: Effect of gender, type 2 diabetes and relationship to post-operative weight loss.

Reduced energy intake drives weight loss following Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) procedures. Post-operative changes in subjective appetite, taste, and smell and food preferences are reported and suggested to contribute to reduced energy intake. We aimed to investigate the prevalence of these changes following RYGB and SG and to evaluate their relationship with weight loss. 98 patients post-RYGB and 155 post-SG from a single bariatric centre were recruited to a cross-sectional study. Participants completed a questionnaire, previously utilised in post-operative bariatric patients, to assess the prevalence of post-operative food aversions and subjective changes in appetite, taste and smell. Anthropometric data were collected and percentage weight loss (%WL) was calculated. The relationship between food aversions, changes in appetite, taste and smell and %WL was assessed. The influence of time post-surgery, gender and type 2 diabetes (T2D) were evaluated. Following RYGB and SG the majority of patients reported food aversions (RYGB = 62%, SG = 59%), appetite changes (RYGB = 91%, SG = 91%) and taste changes (RYGB = 64%, SG = 59%). Smell changes were more common post-RYGB than post-SG (RYGB = 41%, SG = 28%, p = 0.039). No temporal effect was observed post-RYGB. In contrast, the prevalence of appetite changes decreased significantly with time following SG. Post-operative appetite changes associated with and predicted higher %WL post-SG but not post-RYGB. Taste changes associated with and predicted higher %WL following RYGB but not post-SG. There was no gender effect post-RYGB. Post-SG taste changes were less common in males (female = 65%, males = 40%, p = 0.008). T2D status in females did not influence post-operative subjective changes. However, in males with T2D, taste changes were less common post-SG than post-RYGB together with lower %WL (RYGB = 27.5 ± 2.7, SG = 14.6 ± 2.1, p = 0.003). Further research is warranted to define the biology underlying these differences and to individualise treatments

Type 2 diabetes remission 2 years post Roux‐en‐Y gastric bypass and sleeve gastrectomy: the role of the weight loss and comparison of DiaRem and DiaBetter scores

AIMS: The comparative efficacy of Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy on Type 2 diabetes remission and the role of weight loss are unclear. The DiaRem Type 2 diabetes remission prediction score uses HbA1c , age and Type 2 diabetes medications but not Type 2 diabetes duration. The aim of this study was to compare the predictive value of the DiaRem score with the DiaBetter score that includes Type 2 diabetes duration, upon combined (complete plus partial) 2-year post-surgery Type 2 diabetes remission in people following RYGB and sleeve gastrectomy, and to investigate the relationship between weight loss and Type 2 diabetes remission. METHODS: A retrospective single-centre cohort study of obese people with Type 2 diabetes who underwent RYGB (107) or sleeve gastrectomy (103) and a separate validation cohort study (173) were undertaken. Type 2 diabetes remission, per cent weight loss, DiaRem, DiaBetter scores and areas under receiving operator characteristic (ROC) curves were calculated. The relationship between per cent weight loss and Type 2 diabetes remission was investigated using logistic regression with multivariate adjustments. RESULTS: The proportion of people achieving Type 2 diabetes remission was highest for those with the lowest DiaBetter and DiaRem scores, and lowest in those with the highest scores. Areas under the ROC curves were comparable [DiaBetter: 0.867 (95% CI: 0.817-0.916); DiaRem: 0.865 (95% CI: 0.814-0.915), P = 0.856]. Two-year per cent weight loss was higher post RYGB [26.6 (95% CI: 24.8-28.4)] vs post-sleeve gastrectomy [20.6 (95% CI: 18.3-22.8), P < 0.001]. RYGB had 151% higher odds of Type 2 diabetes CR compared with sleeve gastrectomy [OR 2.51 (95% CI: 1.12-5.60), P = 0.025]. This association became non-significant when adjusted for per cent weight loss. CONCLUSION: DiaBetter and DiaRem scores predict Type 2 diabetes remission following RYGB and sleeve gastrectomy. Two-year per cent weight loss plays a key role in determining Type 2 diabetes remission. This article is protected by copyright. All rights reserved

The role of gut hormones in the pathogenesis and management of obesity

The growing obesity epidemic is driving the need for development of novel, effective therapeutic strategies for obesity and its complications. Increasing our understanding of the processes controlling body weight is therefore imperative. Gut hormones have emerged as essential regulators of energy homeostasis. Dysregulation of gut hormone physiology is increasingly implicated in obesity pathogenesis and the compensatory biological responses driving weight regain following energy restriction. Furthermore, gut hormones are among key mediators of the weight loss following Rouxen-Y gastric bypass and sleeve gastrectomy, the bariatric procedures which remain the most effective treatment for severe obesity. Therapeutic strategies targeting gut hormones and their receptors are driving a new pharmacotherapy era and constitute the most promising approach to addressing the obesity epidemic

The role of gut hormones in obesity

The worldwide obesity epidemic represents a severe threat to global health and is driving the scientific quest for a greater understanding of the mechanisms that regulate bodyweight, in order to develop effective preventative and therapeutic strategies. These research efforts have identified gut hormones as key regulators of energy and glucose homeostasis and have implicated them in the pathogenesis of obesity, the weight recidivism that frequently plagues dietary interventions and the marked changes in eating behaviour, weight reduction and metabolic benefits that accompany bariatric surgery. Consequently, therapeutic strategies aimed at modulating gut hormone levels or targeting their receptors are now being used to treat people with obesity and obesity-associated diseases, such as type 2 diabetes, and represent the most promising therapeutic avenue to combat the obesity epidemic