Mechanisms underlying the weight loss effects of RYGB and SG: similar, yet different

The worldwide obesity epidemic continues unabated, adversely impacting upon global health and economies. People with severe obesity suffer the greatest adverse health consequences with reduced life expectancy. Currently, bariatric surgery is the most effective treatment for people with severe obesity, resulting in marked sustained weight loss, improved obesity-associated comorbidities and reduced mortality. Sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB), the most common bariatric procedures undertaken globally, engender weight loss and metabolic improvements by mechanisms other than restriction and malabsorption. It is now clear that a plethora of gastrointestinal (GI) tract-derived signals plays a critical role in energy and glucose regulation. SG and RYGB, which alter GI anatomy and nutrient flow, impact upon these GI signals ultimately leading to weight loss and metabolic improvements. However, whilst highly effective overall, at individual level, post-operative outcomes are highly variable, with a proportion of patients experiencing poor long-term weight loss outcome and gaining little health benefit. RYGB and SG are markedly different anatomically and thus differentially impact upon GI signalling and bodyweight regulation. Here, we review the mechanisms proposed to cause weight loss following RYGB and SG. We highlight similarities and differences between these two procedures with a focus on gut hormones, bile acids and gut microbiota. A greater understanding of these procedure-related mechanisms will allow surgical procedure choice to be tailored to the individual to maximise post-surgery health outcomes and will facilitate the discovery of non-surgical treatments for people with obesity

The role of diet quality in mediating the association between ultra-processed food intake, obesity and health-related outcomes: A review of prospective cohort studies

Prospective cohort studies show that higher intakes of ultra-processed food (UPF) increase the risk of obesity and obesity-related outcomes, including cardiovascular disease, cancer and type 2 diabetes. Whether ultra-processing itself is detrimental, or whether UPFs just have a lower nutritional quality, is debated. Higher UPF intakes are inversely associated with fruit, vegetables, legumes and seafood consumption. Therefore, the association between UPFs and poor health could simply be from excess nutrient intake or from a less healthful dietary pattern. If so, adjustment for dietary quality or pattern should explain or greatly reduce the size of the significant associations between UPFs and health-related outcomes. Here, we provide an overview of the literature and by using a novel approach, review the relative impact of adjusting for diet quality/patterns on the reported associations between UPF intake and health-related outcomes in prospective cohort studies. We find that the majority of the associations between UPFs, obesity and health-related outcomes remain significant and unchanged in magnitude after adjustment for diet quality or pattern. Our findings suggest that the adverse consequences of UPFs are independent of dietary quality or pattern, questioning the utility of reformulation to mitigate against the obesity pandemic and wider negative health outcomes of UPFs

Obesity: when is specialist referral needed?

Obesity is a chronic progressive condition affecting 27% of the UK adult population. Obesity underlies much of primary care workload: 44% of type 2 diabetes (T2D) cases, 23% of ischaemic heart disease, and 41% of certain cancers are attributable to excess BMI.1 Worryingly, the number of adults with severe obesity, which significantly reduces life expectancy, has doubled to approximately 2.6 million over the past decade. Obesity and related illnesses lead to significant healthcare costs, estimated at £6.1 billion per year in the UK, with additional societal costs of £27 billion from reduced productivity secondary to obesity-related ill-health.

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

The Importance of the Gastrointestinal Tract in Controlling Food Intake and Regulating Energy Balance

The gastrointestinal (GI) tract, the key interface between ingested nutrients and the body, plays a critical role in regulating energy homeostasis. Gut-derived signals convey information regarding incoming nutrients to the brain, initiating changes in eating behavior and energy expenditure, to maintain energy balance. Here we review hormonal, neural and nutrient signals emanating from the GI tract and evidence for their role in controlling feeding behavior. Mechanistic studies that have utilized pharmacological and/or transgenic approaches targeting an individual hormone/mediator have yielded somewhat disappointing bodyweight changes, often leading to the hormone/mediator in question being dismissed as a potential obesity therapy. However, the recent finding of sustained weight-reduction in response to systemic administration of a long-acting analog of the gut-hormone glucagon-like peptide-1 (GLP-1) highlights the therapeutic potential of gut-derived signals acting via non-physiological mechanisms. Thus, we also review therapeutics strategies being utilized or developed to leverage GI signals in order to treat obesity

Potential mechanisms underlying the effect of bariatric surgery on eating behaviour

PURPOSE OF REVIEW: Reduced energy intake, resulting from favourable changes in eating behaviour, is the predominant driver of weight loss following bariatric surgery. Here we review the most recent studies examining the impact of Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy, the two most common bariatric procedures, upon eating behaviour and the suggested underlying biological mechanisms. RECENT FINDINGS: Following RYGB or sleeve gastrectomy, most people report subjective changes in appetite, taste and food preference, with decreased high-fat preference most commonly reported. Objective postsurgery changes in taste and olfactory acuity occur. A new phenomenon, 'meal-size aversion', may contribute to reduced postoperative energy intake. Recent studies provide evidence for peptide YY3-36, glucagon-like peptide-1, ghrelin, neurotensin and oleoylethanolamide as mediators of postoperative eating behaviour changes. Factors modulating these changes include sex, type 2 diabetes status, genetics and bariatric procedure. New studies implicate central dopaminergic and opioid receptor signalling as key neural mediators driving altered eating behaviour. Brain neuroimaging studies show that obesity-associated changes in food-cue responses, brain connectivity and structural abnormalities are normalized following bariatric surgery. SUMMARY: Understanding the biological mechanisms mediating the eating behaviour changes engendered by bariatric surgery may lead to the development of novel therapeutic strategies for people with obesity

Inhibition of food intake in obese subjects by peptide YY3-36

Background: The gut hormone fragment peptide YY3-36 (PYY) reduces appetite and food intake when infused into subjects of normal weight. In common with the adipocyte hormone leptin, PYY reduces food intake by modulating appetite circuits in the hypothalamus. However, in obesity there is a marked resistance to the action of leptin, which greatly limits its therapeutic effectiveness. We investigated whether obese subjects were also resistant to the anorectic effects of PYY.Methods: We compared the effects of PYY infusion on appetite and food intake in 12 obese and 12 lean subjects in a double-blind, placebo-controlled, crossover study. The plasma levels of PYY, ghrelin, leptin, and insulin were also determined.Results: Caloric intake during a buffet lunch offered two hours after the infusion of PYY was decreased by 30 percent in the obese subjects (P<0.001) and 31 percent in the lean subjects (P<0.001). PYY infusion also caused a significant decrease in the cumulative 24-hour caloric intake in both obese and lean subjects. PYY infusion reduced plasma levels of the appetite-stimulatory hormone ghrelin. Endogenous fasting and postprandial levels of PYY were significantly lower in obese subjects (the mean [+/-SE] fasting PYY levels were 10.2+/-0.7 pmol per liter in the obese group and 16.9+/-0.8 pmol per liter in the lean group, P<0.001). Furthermore, the fasting PYY levels correlated negatively with the body-mass index (r=-0.84, P<0.001).Conclusions: We found that obese subjects were not resistant to the anorectic effects of PYY. Endogenous PYY levels were low in the obese subjects, suggesting that PYY deficiency may contribute to the pathogenesis of obesity

Mechanisms of weight regain

Weight regain following weight loss is frequent problem that people with obesity face. This weight recidivism is often attributed to the lack of compliance with appropriate food habits and exercise. On the contrary, it is known that body weight and fat mass are regulated by numerous physiological mechanisms, far beyond voluntary food intake and physical exercise. Thus, the aim of this paper is to review the main peripheral and central mechanisms involved in weight regain. Gut hormone secretion profiles impact upon predisposition to weight regain according to an individual variability, although it is recognised a usual pattern of compensatory changes: a reduction in anorectic hormones secretion and an increase in orexigenic hormone. These changes lead to both increased appetite and reward value of food leading to increased energye intake. In addition, resting energy expenditure after weight loss is lower than expected according to body composition changes. This gap between observed and predicted energy expenditure following weight loss is named metabolic adaptation, which has been suggested to explain partly weight regain. This complicated scenario, beyond patient motivation, makes weight regain a challenge in long-term management interventions in patients with obesity