Safe, effective treatments that are more widely available than surgery are needed to combat obesity. Nonetheless, the FDA has voted against two new drugs and withdrawn another in 2010. Despite the uphill battle faced by those developing medical therapies, a number of studies demonstrate the variety of biological targets for obesity treatment.

The SHAPE (Screened Health Assessment and Pacer Evaluation) trial was a 24 month randomized multicenter placebo‐controlled study to determine the efficacy of an implantable gastric stimulator (IGS) for weight loss. This report is an investigator‐initiated sub‐study at one site designed to assess whether IGS affects plasma levels of ghrelin and peptide YY (PYY). The device was implanted in all subjects but was activated in the Treatment group (n = 7, BMI = 41.5 ± 2.0 kg/m2) and remained inactive in the Control (n = 6, BMI = 39.5 ± 1.7 kg/m2) during the first 12 months. IGS was activated in both groups during months 12–24. Fasting venous blood was drawn at months 0, 12, and 24 and an oral glucose tolerance test (OGTT) was performed at month 12. Although there was no difference in weight loss at 6 months (Control: −6.6 ± 1.5% vs. Treatment: −6.2 ± 1.4%), at 24 months the Control group exhibited weight gain from baseline (+2.2 ± 1.5%) that was significantly different from the weight loss in the Treatment group (−1.9 ± 1.4%; P < 0.05). At 12 months, fasting ghrelin was significantly increased (P < 0.05) in the Treatment group (285 ± 35 to 336 ± 35 pg/ml; weight change, −4.9 ± 1.4%), but not in the Control (211 ± 36 to 208 ± 35 pg/ml; weight change, −3.4 ± 1.5%). No significant change was observed in postprandial suppression of plasma ghrelin or in fasting and postprandial PYY levels. In conclusion, IGS does not prevent the increase in fasting plasma ghrelin levels associated with weight loss. Further studies are needed to determine whether changes in technology can improve weight loss and maintenance, perhaps using gut hormones as biomarkers of possible efficacy.

ObesityVolume 18, Issue S2 p. S204-S204 Free Access Poster Abstracts–Monday, October 11, 2010 First published: 06 September 2012 https://doi.org/10.1038/oby.2010.162AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume18, IssueS2Special Issue: OBESITY 2010 Abstract SupplementNovember 2010Pages S204-S204 RelatedInformation

The obesity epidemic is a global issue and shows no signs of abating, while the cause of this epidemic remains unclear. Marketing practices of energy-dense foods and institutionally-driven declines in physical activity are the alleged perpetrators for the epidemic, despite a lack of solid evidence to demonstrate their causal role. While both may contribute to obesity, we call attention to their unquestioned dominance in program funding and public efforts to reduce obesity, and propose several alternative putative contributors that would benefit from equal consideration and attention. Evidence for microorganisms, epigenetics, increasing maternal age, greater fecundity among people with higher adiposity, assortative mating, sleep debt, endocrine disruptors, pharmaceutical iatrogenesis, reduction in variability of ambient temperatures, and intrauterine and intergenerational effects as contributing factors to the obesity epidemic are reviewed herein. While the evidence is strong for some contributors such as pharmaceutical-induced weight gain, it is still emerging for other reviewed factors. Considering the role of such putative etiological factors of obesity may lead to comprehensive, cause specific, and effective strategies for prevention and treatment of this global epidemic.

The endogenous cannabinoid system has been identified as playing a central role in the regulation of energy homeostasis, and its overactivity has been associated with obesity. Rimonabant is a selective endocannabinoid CB1 receptor antagonist that has been shown to be an effective treatment for obesity and cardiometabolic risk factors. Studies comparing 20 mg/d of rimonabant with placebo show a placebo-subtracted weight loss between 6.3 and 6.9 kg at 1 year. In addition to the health benefits already associated with weight loss, rimonabant has shown additional improvements in lipid and glycemic cardiometabolic biomarkers such as low-density lipoprotein cholesterol, triglycerides, C-reactive protein, glucose, and adiponectin. The use of endocannabinoid antagonists such as rimonabant provides a promising therapeutic approach to the treatment of obesity and its associated cardiometabolic risks.

BACKGROUND Food reinforcement and dopaminergic activity may influence food consumption, but research on whether they interact has not been performed. OBJECTIVE We assessed the effects of food reinforcement and the interaction of food reinforcement with the dopamine transporter (SLC6A3) genotype and the dopamine D(2) receptor (DRD(2)) genotype on energy consumption. DESIGN We studied food-consumption and reinforcing-value-of-food tasks in 88 smokers of European ancestry before they enrolled in smoking-cessation treatment. In the food-consumption task, subjects tasted and consumed 8 snack foods ad libitum. The reinforcing-value-of-food task assessed how hard subjects would work for food. RESULTS Significant interactions between dopamine genotypes and food reinforcement were observed. Subjects high in food reinforcement who lacked an SLC6A3*9 allele consumed significantly more calories (>150 kcal; P = 0.015) than did subjects low in food reinforcement or those high in food reinforcement who carried at least one SLC6A3*9 allele. Similarly, subjects high in food reinforcement who carried at least one DRD(2)*A1 allele consumed >130 kcal more (P = 0.021) than did subjects low in food reinforcement or those high in food reinforcement who lacked a DRD(2)*A1 allele. There was also a main effect of food reinforcement on energy intake (P = 0.005), with subjects high in food reinforcement consuming 104 kcal (or 30%) more than did subjects low in food reinforcement. CONCLUSIONS Food reinforcement has a significant effect on energy intake, and the effect is moderated by the dopamine loci SLC6A3 and DRD(2).

Both the hedonic ratings and the reinforcing value of food have been considered to be determinants of food intake. The objective of this study was to compare the pleasurable ratings and the reinforcing value of food as determinants of energy intake. Seventy-four smokers were studied in food consumption and reinforcing value of food tasks prior to enrolling in a smoking-cessation treatment program. For the food consumption task, the participants tasted and consumed food ad lib from eight snack foods. The reinforcing value of the food task assessed how hard subjects would work for a preferred snack food. Results showed that food reinforcement was related to laboratory food intake, with those high in food reinforcement consuming significantly more calories (+114.4 kcal, P<.01) than did the participants low in food reinforcement. Food reinforcement was related to food intake for the preferred food as well as to total energy intake. Hedonics for the preferred food was related to food reinforcement but not to either measure of laboratory energy intake. In multiple-regression models, food reinforcement and the interaction of food reinforcement by sex were significant predictors of energy intake for the preferred food and for total energy intake, along with baseline hunger. In conclusion, energy intake in smokers in a laboratory setting is more strongly related to food reinforcement than to the hedonic ratings of food.

Objective: To determine whether dietary restraint modifies stress-induced eating in youth.Research Methods and Procedures: Snacking was measured in boys (9.5 +/- 0.3 years) and girls (9.0 +/- 0.3 years), with and without dietary restraint, across a control day after reading children's magazines and/or coloring, and on a stress day after giving a videotaped speech, with order of conditions counterbalanced. Children were divided into four groups based on dietary restraint and changes in perceived stress: low-restraint/low-reactive (n = 9), low-restraint/ high-reactive (n = 13), high-restraint/low-reactive (n = 10), and high-restraint/high-reactive (n = 8). Body composition was estimated by skinfolds.Results: Energy intake of snack foods was influenced differently by dietary restraint and stress reactivity in the stress and control conditions (p < 0.01). After being stressed, low-restraint/low-reactive children ate fewer snacks and high-restraint/high-reactive children ate more snacks compared with the control condition. After covarying for percentage of body fat, the interactions remained (p < 0.01). Girls ate less than boys (p < 0.001), but sex did not influence eating in control and stress conditions.Discussion: Dietary restraint occurs in children and may influence the effect of stress on eating. Interpersonal stress decreases snacking in low dietary restrained youth but increases snacking in high dietary restrained children, perhaps because of stress-induced disinhibition.