then displaces the significant amount of active R* form towards R, in the absence of stimulation. Inverse agonists stabilize the inactive form of these receptors. In brief, agonists enrich R* whereas inverse agonists stabilize R, while antagonists equilibrate R/R*. However, the physiological conse- quences of the R*/R transition (‘toggling’) remains unknown. Since stim- ulating 5-HTR4 in the NAc favors anorexia, we hypothesized that the two extremes of the 5-HTR* 4 /5-HTR 4 in the NAc correspond to two extremes of feeding patterns: restrictive diet and overeating. Activation of the main signaling pathway (cAMP/PKA) of 5-HTR4 in the NAc (R*) inhibits feeding. Inactivating 5-HTR 4 totally by injecting a specific inverse agonist of 5-HTR 4 in freely moving mice causes overeating. From R* to R, cAMP levels in- crease and then decrease in the NAc. Downstream, activation of 5-HTR4 in the NAc promotes anorexia because the levels of an anorectic peptide CART increase following activation of a rewarding signaling pathway (cAMP/PKA signaling pathway). Silencing R5-HT 4 decreases CART and increases the mRNA levels of NPY, an orexigenic peptide in the NAc. siRNA-mediated NPY knock-down in the NAc suppresses overeating induced by the total inactivation of 5-HTR4. The absence of 5-HTR4 “hijacks” cocaine abuse to excessive food intake. Selecting one's addiction may then depend on the activity state of 5-HTR4. Accordingly, the equilibrium of R*/R in the reward system, specifically in the NAc, contributes to the motivation to eat regardless of the energy requirement, resulting in a new aspect of eating behavior. It is therefore conceivable that 5-HTR 4 -specific ligands, in asso- ciation with psychological treatment, will be useful in coping with the stressors that trigger eating disorders. GUT MICROBIOTA MODULATES INTESTINAL SIGNALLING IN OBESITY M. Covasa 1, 2, 3 . 1 French National Institute for Agricultural Research, INRA, Jouy-en-Josas, France; 2 College of Osteopathic Medicine, Western University of Health Sciences, Pomona, CA, USA; 3 Department of Health and Human Development, University “Stefan cel Mare”, Suceava, Romania mcovasa@jouy.inra.fr Among the long list of factors contributing to obesity, deficits in satiation signalling have been shown to contribute to passive overconsumption and development of obesity. Further, emerging evidence demonstrates that gut signalling mechanisms involved in control of food intake and regulation of energy balance are modulated by the trillions of bacteria inhabiting the gastrointestinal tract. Using an animal model that reflects human obesity, we demonstrated that animals prone to obesity (OP) are less sensitive to the inhibitory effects of intraduodenal nutrients compared to their obese resistant (OR) counterparts. High fat (HF) feeding, but not chow, dimin- ished the suppressive effects of intraduodenal ensure, glucose and intra- lipid in OP compared to OR. This reduced sensitivity to nutrients is an early consequence of HF-feeding in OP rats, resulting in rapid impairments in nutrient-induced satiation through blunted responses in endogenous GLP- 1 and hindbrain vagal afferent signaling. The mechanisms by which gut microbiota interacts with the host to affect the myriad of factors control- ling food intake and energy balance are either not known or poorly un- derstood. We showed that mice lacking gut microbiota (GF) overconsume calories from nutritive sweet and lipid solutions, a phenomenon associ- ated with changes in peptide secretion and intestinal nutrient sensing molecules such as T1R3, CD36, GPR40, GPR120 and Fiaf. These findings show that absence of gut microflora leads to pronounced changes in peptides secretion and intestinal nutrient sensing components. We also showed that OP rats have a distinct gut microbiota profile from OR, with a high Firmicutes-to-Bacteroidetes ratio and high levels of bacteria from the Ruminococcus genus, which is known to break down polysaccharides promoting monosaccharide absorption, enhanced lipogenesis, and lipid storage. To determine the contribution of microbiota to the development of obesity, we conventionalized GF mice with OP and OR fecal samples. After 8wks of HF feeding, GF-OP mice had increased weight gain, adiposity, and food intake compared to GF-OR mice. In the intestine, we found decreased levels of satiety peptides, along with altered G-protein coupled nutrient responsive receptors that mediate release of these peptides, indicating a reduction in overall nutrient-induced satiety accounting for their observed hyperphagia. Further, we found that in OP and GF-OP ani- mals, p-MLC, ZO-1, and occludin, all markers of gut permeability, were increased, and this was associated with increased circulating cytokines. In liver and WAT, we observed increased inflammation, and enhanced activation of the proinflammatory NF-kB/IKKb pathway. Furthermore, expression of PPARg, a nuclear receptor that regulates fatty acid storage, was elevated, as were several enzymes controlled by the PPARg pathway, all of which ultimately contribute to promotion of adipogenesis and lipogenesis. Finally, conventionalization resulted in increased hypotha- lamic inflammation and altered expression of central POMC/CART and AgRP/NPY peptides in GF-OP, mimicking the OP donor rats. Together, these results demonstrate that gut microbiota, through yet unidentified encod- ing elements, can influence and alter complex molecular signaling ma- chinery responsible for modulating host metabolism, intestinal nutrient sensing, and energy-storing signaling pathway information, all of which are involved in control of food intake and regulation of body weight. Roux- en-Y gastric bypass (RYGB) is the most effective treatment for severe obesity. We found significant changes in gut microbiota profile after RYGB with an overall decrease of Firmicutes and an augmentation of Proteo- bacteria and Actinobacteria. Thus anatomical reorganization following RYGB results in long term shifts in gut microbiota composition that may influence gut peptide synthesis and release and contribute to weight loss maintenance. NEURAL AND BEHAVIORAL MECHANISMS UNDERLYING THE PORTION SIZE EFFECT IN CHILDREN K.L. Keller, S.N. Fearnbach, L.K. English. Department of Nutritional Sciences, The Pennsylvania State University, University Park, PA 16802, USA klk37@psu.edu Portion sizes of foods served inside and outside the home have increased over the past several decades. Epidemiological data suggest a positive association between portion size and obesity. One explanation for this association may be the portion size effect (PSE)da robust phenomenon that the amount of food served is positively associated with the amount eaten, which has been demonstrated with several food types in a variety of set- tings. However, the mechanisms of this effect are not known. We argue that understanding the mechanisms underlying the relationship between portion size and intake is necessary before successful interventions can be developed to reduce energy intake. Possible mechanisms previously tested involve visual cues, bite size adjustment, serving vessel size, and post- ingestive learning. Despite ongoing research in this area, mechanisms remain unclear. The current study has approached this issue by using functional magnetic resonance imaging (fMRI) to investigate the brain mechanisms underlying the PSE. Foods shown in previous neuroimaging paradigms differed by palatability, portion size, packaging, and food type. To address these con- cerns, we created a series of food images that varied at two conditions of portion size (large and small) and energy density (ED; <1.5 kcal/g and >1.5 kcal/g). Foods were selected from the Continuing Survey of Food Intake in Individuals, photographed at the 10th and 90th percentiles of amounts commonly consumed, and presented at a child-appropriate angle. We attempted to balance type (entr ees vs. snacks) and taste quality (sweet vs. savory). The final paradigm consisted of four food stimuli con- ditions (large high ED, small high ED, large low ED, small low ED) and two control conditions (furniture and scrambled images). Children viewed images in a block design in a Siemen's 3T fMRI scanner. In addition, we assessed the PSE across 4 randomized, multi-item laboratory meals of high (e.g., macaroni and cheese, garlic bread) and low (e.g., grapes, tomatoes) ED foods varying in portion size (100%, 133%, 167%, and 200%). This talk includes preliminary results from our first hypothesis, that portion size of the food images would modulate brain response in regions associated with executive function, reward, motivation, working memory, and spatial integration. Uncorrected whole brain analyses for the large vs. small portion contrast revealed activation in regions involved in inhibition (e.g., dorsolateral prefrontal cortex), reward (e.g., insula) and processing of appetitive stimuli (e.g. cerebellum) but only the cerebellum survived correction for multiple testing. Several brain regions survived whole brain correction when BOLD activation was compared between the high vs. low ED contrast (e.g. left anterior cingulate, thalamus). Region-of-interest (ROI) analyses (uncorrected for multiple tests) on brain regions previously implicated in the food-related imaging literature showed bilateral acti- vation in the inferior frontal gyrus, in response to large vs. small portion Abstracts / Appetite 96 (2016) 642e644 643