Obesity and addiction: can a complication of surgery help us understand the connection?

Obesity is a multifactorial, chronic disease that has proven difficult to treat. An increased understanding of aetiological mechanisms is critical to the development of more effective obesity prevention and treatment strategies. A growing body of empirical evidence has demonstrated parallels between obesity, overeating and substance abuse, including shared behavioural, psychological and neurophysiological factors implicated in the excessive intake of both food and substances of abuse. Several different lines of research have recently emerged that hold the potential to shed light on the connection between obesity, food reward and addiction, with studies examining changes in alcohol use/misuse after weight loss surgery providing a particularly interesting perspective on these interrelationships. However, these lines of investigation have proceeded in relative isolation, and relevant research findings have yet to be integrated in a synthesized, comprehensive manner. To provide an opportunity to achieve such a synthesis, a scientific symposium was convened at the Radcliffe Institute in Cambridge, Massachusetts. Invited participants were researchers working in diverse domains related to the intersection between obesity and addiction. Extensive discussion was generated suggesting novel research directions. In this article, we summarize and synthesize the symposium participants' ongoing research in this area, incorporating additional relevant research holding potential clues regarding the connections between obesity, weight loss surgery and addiction.

Alzheimer's Prevention Education: If We Build It, Will They Come? www.AlzU.org.

BACKGROUND: Internet-based educational interventions may be useful for impacting knowledge and behavioral change. However, in AD prevention, little data exists about which educational tools work best in terms of learning and interest in participating in clinical trials. OBJECTIVES: Primary: Assess effectiveness of interactive webinars vs. written blog-posts on AD prevention learning. Secondary: Evaluate the effect of AD prevention education on interest in participating in clinical trials; Assess usability of, and user perceptions about, an online AD education research platform; Classify target populations (demographics, learning needs, interests). DESIGN: Observational. SETTING: Online. PARTICIPANTS: Men/Women, aged 25+, recruited via facebook.com. INTERVENTION: Alzheimer's Universe (www.AlzU.org) education research platform. MEASUREMENTS: Pre/post-test performance, self-reported Likert-scale ratings, completion rates. RESULTS: Over two-weeks, 4268 visits were generated. 503 signed-up for a user account (11.8% join rate), 196 participated in the lessons (39.0%) and 100 completed all beta-testing steps (19.9%). Users randomized to webinar instruction about AD prevention and the stages of AD demonstrated significant increases (p=0.01) in pre vs. post-testing scores compared to blog-post intervention. Upon joining, 42% were interested in participating in a clinical trial in AD prevention. After completing all beta-test activities, interest increased to 86%. Users were primarily women and the largest category was children of AD patients. 66.3% joined to learn more about AD prevention, 65.3% to learn more about AD treatment. CONCLUSIONS: Webinar-based education led to significant improvements in learning about AD prevention and the stages of AD. AlzU.org participation more than doubled interest in AD prevention clinical trial participation. Subjects were quickly and cost-effectively recruited, and highly satisfied with the AD education research platform. Based on these data, we will further refine AlzU.org prior to public launch and aim to study the effectiveness of 25 interactive webinar-based vs. blog-post style lessons on learning and patient outcomes, in a randomized, within-subjects design trial.

Pre-bariatric surgery weight loss requirements and the effect of preoperative weight loss on postoperative outcome.

Pre-bariatric surgery requirements vary between surgeons and surgical centers, with standards of practice not yet established. The goal of this systematic review was to summarize and evaluate the available literature on pre-bariatric surgery weight loss requirements and the relation between preoperative weight loss and postoperative outcome. Major databases, including Medline, PubMed and PsychINFO were searched for relevant articles. Case studies, studies>20 years old and studies that utilized self-reported body weight data were excluded. Data on the effect of the following was summarized: (1) preoperative requirements on preoperative weight loss; (2) insurance-mandated preoperative requirements; (3) the contingency of receipt of surgery; (4) preoperative weight loss on postoperative weight loss and (5) preoperative weight loss on perioperative and postoperative complication and comorbidity rates. The majority of studies suggest that: (1) current preoperative requirements held by the majority of third party payer organizations in the United States are ineffective in fostering preoperative weight loss; (2) making receipt of surgery contingent upon achieving preoperative weight loss, and meal-replacement diets, may be particularly effective in fostering preoperative weight loss and (3) preoperative weight loss may lead to improvements in at least some relevant postoperative outcomes. However, a preoperative weight loss mandate may lead to the denial of surgery and subsequent health benefits to individuals who are unable to achieve a prespecified amount of weight. Overall, the limited number and quality of prospective studies in this area prohibits the much-needed establishment of standards of practice for pre-bariatric requirements.

Relation between changes in neural responsivity and reductions in desire to eat high-calorie foods following gastric bypass surgery.

Reductions in reward-related (e.g. striatal) neural activation have been noted following obesity surgery. It has been speculated that these postoperative neural changes may be related to documented postoperative changes in food preferences; however, this relation has not been previously established. In this study, functional magnetic resonance imaging and rating scales were used to assess neural responsivity, desire to eat (i.e. wanting), and liking for high- and low-calorie food cues in 14 females one month pre- and one month post-Roux-en-Y gastric bypass (RYGB) surgery. Pre- to post-RYGB changes in all variables were assessed, and postoperative changes in neural responsivity were regressed on postoperative changes in desire to eat and liking of foods. Results revealed significant postoperative reductions in mesolimbic (e.g. striatal) neural responsivity, desire to eat (wanting), and liking for high- relative to low-calorie food cues. Postoperative reductions in mesolimbic responsivity were associated with postoperative reductions in wanting, but not liking, for high- versus low-calorie foods. Interestingly, reductions in food wanting were also related to reductions in inhibitory (e.g. dorsolateral prefrontal cortex) activation following RYGB. Results are consistent with the hypothesized delineation between wanting and liking, supporting the notion that wanting, but not liking, is processed through the dopaminergic reward pathway. Concurrent reductions in both reward-related and inhibitory activation-predicted reductions in desire to eat might suggest that less dietary inhibition was elicited to resist potential overconsumption as the anticipated reward value of high-calorie foods decreased following RYGB.

Neuroimaging and obesity: current knowledge and future directions.

Neuroimaging is becoming increasingly common in obesity research as investigators try to understand the neurological underpinnings of appetite and body weight in humans. Positron emission tomography (PET), functional magnetic resonance imaging (fMRI) and magnetic resonance imaging (MRI) studies examining responses to food intake and food cues, dopamine function and brain volume in lean vs. obese individuals are now beginning to coalesce in identifying irregularities in a range of regions implicated in reward (e.g. striatum, orbitofrontal cortex, insula), emotion and memory (e.g. amygdala, hippocampus), homeostatic regulation of intake (e.g. hypothalamus), sensory and motor processing (e.g. insula, precentral gyrus), and cognitive control and attention (e.g. prefrontal cortex, cingulate). Studies of weight change in children and adolescents, and those at high genetic risk for obesity, promise to illuminate causal processes. Studies examining specific eating behaviours (e.g. external eating, emotional eating, dietary restraint) are teaching us about the distinct neural networks that drive components of appetite, and contribute to the phenotype of body weight. Finally, innovative investigations of appetite-related hormones, including studies of abnormalities (e.g. leptin deficiency) and interventions (e.g. leptin replacement, bariatric surgery), are shedding light on the interactive relationship between gut and brain. The dynamic distributed vulnerability model of eating behaviour in obesity that we propose has scientific and practical implications.

Changes in neurohormonal gut peptides following bariatric surgery.

The rising prevalence of obesity has reached pandemic proportions, with an associated cost estimated at up to 7% of health expenditures worldwide. Bariatric surgery is currently the only effective long-term treatment for obesity and obesity-related co-morbidities in clinically severely obese patients. However, the precise physiological mechanisms underlying the postsurgical reductions in caloric intake and body weight are poorly comprehended. It has been suggested that changes in hormones involved in hunger, food intake and satiety via the neurohormonal network may contribute to the efficacy of bariatric procedures. In this review, we consider how gastrointestinal hormone concentrations, involved in appetite and body weight regulation via the gut-brain axis, are altered by different bariatric procedures. Special emphasis is placed on neurohormonal changes following Roux-en-Y gastric bypass surgery, which is the most common and effective procedure used today.

Neuroimaging, gut peptides and obesity: novel studies of the neurobiology of appetite.

Two major biological players in the regulation of body weight are the gut and the brain. Peptides released from the gut convey information about energy needs to areas of the brain involved in homeostatic control of food intake. There is emerging evidence that human food intake is also under the control of cortical and subcortical areas related to reward and cognition. The extent to which gut hormones influence these brain areas is not fully understood. Novel methods combining the study of neural activity and hormonal signalling promise to advance our understanding of gut-brain interactions. Here, we review a growing number of animal and human studies using neuroimaging methods (functional magnetic resonance imaging, positron emission tomography) to measure brain activation in relation to nutrient loads and infusion of gut peptides. Implications for current and future pharmacological treatments for obesity are discussed.