Christopher N. Ochner

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.

Selective Reduction in Neural Responses to High Calorie Foods Following Gastric Bypass Surgery

Objective:To investigate changes in neural activation and desire to eat in response to appetitive cues from pre- to postbariatric surgery for obesity. Background:Roux-en-Y gastric bypass (RYGB) is the most common bariatric procedure. However, the mechanisms of action in RYGB are not well understood. A significant proportion of the resulting reduction in caloric intake is unaccounted for by the restrictive and malabsorptive mechanisms and is thought to be mediated by neuroendocrine function. Numerous investigations of postsurgical changes in gut peptides have resulted; however, changes in neural activation after RYGB surgery have not been previously investigated. METHODS:Functional magnetic resonance imaging and verbal rating scales were used to assess brain activation and desire to eat in response to high- and low-calorie food cues in 10 female patients 1-month pre- and post-RYGB surgery. Results:Postsurgical reductions in brain activation were found in key areas within the mesolimbic reward pathway, which were significantly more pronounced in response to food cues that were high (vs. low) in caloric density. These changes mirrored concurrent postsurgical reductions in desire to eat, which were also greater in response to food cues that were high versus low in caloric density (P = 0.007). Conclusions:Findings support the contention that RYGB surgery leads to substantial changes in neural responses to food cues encountered in the environment, provide a potential mechanism for the selective reduction in preferences for high-calorie foods, and suggest partial neural mediation of changes in caloric intake seen after RYGB surgery.

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.

Neural responsivity to food cues in fasted and fed states pre and post gastric bypass surgery.

Reductions in mesolimbic responsivity have been noted following Roux-en-Y gastric bypass (RYGB; Ochner et al., 2011a). Given potential for postoperative increases in postprandial gut (satiety) peptides to affect mesolimbic neural responsivity, we hypothesized that: (1) post RYGB changes in mesolimbic responsivity would be greater in the fed relative to the fasted state and; (2) fasted vs. fed state differences in mesolimbic responsivity would be greater post-relative to pre-surgery. fMRI was used to asses neural responsivity to high- and low-calorie food cues in five women 1 mo pre- and 1 mo post-RYGB. Scans were repeated in fasted and fed states. Significant post RYGB decreases in the insula, ventromedial prefrontal cortex (vmPFC) and dorsolateral prefrontal cortex (dlPFC) responsivity were found in the fasted state. These changes were larger than neural changes in the fed state, which were non-significant. Preoperatively, fasted vs. fed differences in neural responsivity were greater in the precuneus, with large but nonsignificant clusters in the vmPFC and dlPFC. Postoperatively, however, no fasted vs. fed differences in neural responsivity were noted. Results were opposite to that predicted and appear inconsistent with the initial hypothesis that postoperative increases in postprandial gut peptides are the primary driver of postoperative changes in neural responsivity.

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.

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.

The neurohormonal regulation of energy intake in relation to bariatric surgery for obesity

Obesity has reached pandemic proportions, with bariatric surgery representing the only currently available treatment demonstrating long-term effectiveness. Over 200,000 bariatric procedures are performed each year in the US alone. Given the reliable and singular success of bariatric procedures, increased attention is being paid to identifying the accompanying neurohormonal changes that may contribute to the resulting decrease in energy intake. Numerous investigations of postsurgical changes in gut peptides have been conducted, suggesting greater alterations in endocrine function in combination restrictive and malabsorptive procedures (e.g., Roux-en-Y gastric bypass) as compared to purely restrictive procedures (e.g., gastric banding), which may contribute to the increased effectiveness of combination procedures. However, very few studies have been performed and relatively little is known about changes in neural activation that may result from bariatric procedures, which likely interact with changes in gut peptides to influence postsurgical caloric intake. This review provides a background in the neurohormonal regulation of energy intake and discusses how differing forms of bariatric surgery may affect the neurohormonal network, with emphasis on Roux-en-Y gastric bypass, the most commonly performed procedure worldwide. The paper represents an invited review by a symposium, award winner or keynote speaker at the Society for the Study of Ingestive Behavior [SSIB] Annual Meeting in Portland, July 2009.

Effectiveness of a Prebariatric Surgery Insurance-required Weight Loss Regimen and Relation to Postsurgical Weight Loss

Most US insurance companies require patients to participate in a medically supervised weight loss regimen prior to bariatric surgery. However, the utility of this requirement has not been documented. Data was collected from 94 bariatric surgery patients who were required, and 59 patients who were not required, by their insurance company to participate in a presurgical weight loss regimen. Weight change in the required group, as well as group differences in weight change, was examined from 3 and 6 months presurgery to 1 week presurgery, and from 1 week presurgery to 3 months postsurgery. Weight change presurgery was then used to predict weight loss postsurgery. In the 6 months prior to surgery, required patients gained 3.7 kg ± 5.9 (s.d.) (P < 0.0005), which did not differ from nonrequired patients. From surgery to 3 months postsurgery, required patients lost 23.6 ± 8 kg (P < 0.0005), also without differing from nonrequired patients. Patients who gained more weight prior to surgery, lost more weight postsurgery (P = 0.001), while controlling for initial weight. Findings suggest that the common weight loss regimen requirements of US insurance carriers were ineffective in producing presurgical weight loss in this sample. Most patients (>70%) in this sample gained weight prior to surgery, potentially taking advantage of final opportunities to overindulge in preferred foods. Required patients fared no better in terms of weight change postsurgically and, surprisingly, presurgical weight gain predicted better postsurgical weight loss outcome. Several potential explanations for this finding are offered.

Effect of preoperative body mass index on weight loss after obesity surgery

BACKGROUND Previous studies suggest that individuals with body mass index (BMI) above versus below 60 kg/m(2) attain lower percentage of excess weight loss (%EWL) after bariatric surgery. The objectives of this study were to (1) test whether conclusions drawn about the effect of preoperative BMI on postoperative weight loss depend on the outcome measure, (2) test for evidence of a threshold effect at BMI = 60 kg/m(2), and (3) test the effect from surgery to 12-month follow-up, relative to 12- to 36-month follow-up. METHODS Retrospective analyses of participants grouped according to preoperative BMI: 35-39.9 (n = 232); 40-49.9 (n = 1166); 50-59.9 (n = 429);≥60 (n = 166). RESULTS As anticipated, individuals with higher versus lower preoperative BMI had greater total weight loss but lower %EWL at all postoperative time points (all, P<.0005). However, these individuals also had lower percentage of initial weight loss (%IWL) at all time points beyond 1 month postsurgery (all, P<.0005). From 12- to 36-months, individuals with BMI 35-39.9 had 3.2±14.3 %IWL (P<.0001); 40-49.9 had 1.0±8.9 %IWL (P<.0005); 50-59.9 had-2.4±10.0 %IWL (P<.0005); and≥60 had-3.6±11.5 %IWL (P<.0005). Overall F3,1989 = 20.2, P< .0005. CONCLUSIONS Conclusions drawn about the effect of preoperative BMI may depend on the outcome measure. A dosage effect of preoperative BMI was apparent, with heavier individuals showing lower percentages of initial and excess weight loss, regardless of BMI above or below 60 kg/m(2). Finally, this effect was particularly apparent after the initial 12-month rapid weight loss phase, when less obese (BMI<50) individuals continued losing weight, while heavier individuals (BMI≥50) regained significant weight.

Obesity-Related Hormones and Metabolic Risk Factors: A Randomized Trial of Diet Plus Either Strength or Aerobic Training versus Diet Alone in Overweight Participants

There is debate about the additive effects of exercise in conjunction with diet to treat obesity, and not much is known about the differential effects of strength versus aerobic training. This randomized controlled trial examined the effects of diet plus strength training, diet plus aerobic training, or diet only on metabolic risk factors associated with obesity. Eighty-one overweight and obese participants completed the 8-week intervention. All participants received an energy-restrictive formula diet with an energy content based on 70% of measured resting metabolic rate (RMR). Participants assigned to an exercise group trained 3 days/week under supervision. Anthropometrics and fasting hormones were assessed pre- and post-intervention. Mean weight loss (8.5 ± 4.3kg SD) did not differ between groups nor did reductions in BMI or body fat, although the diet plus strength training group showed marginally greater lean mass retention. There were significant improvements in the values and number of metabolic syndrome risk factors, and decreases in insulin concentrations and insulin resistance, which did not vary between groups. For men, testosterone increased significantly more in the diet plus aerobic training as compared to the other groups. As compared to diet alone, the addition of strength or aerobic training did not improve changes in BMI, body fat or metabolic risk factors although the diet plus strength training group showed a trend toward preservation of lean mass, and the diet plus aerobic group in men resulted in increased testosterone concentrations.