Thesis advisor: Barbara E. Wolfe / The core defining features of bulimia nervosa (BN) are repeated binge eating episodes and compensatory purging behavior. The biobehavioral aspects of binge eating are complex and not fully understood. One area of recent interest is the role of the satiety-signaling peptide cholecystokinin (CCK). Previous research observed a blunted postprandial plasma CCK response in those with BN, therefore suggesting this may be a cause, consequence, or maintenance factor in binge eating. It is unknown whether this altered response is due to a state versus trait phenomenon, thus having implications in the development of clinical treatment strategies. To examine the nature of this altered response, this study assessed whether CCK normalizes following remission from BN (RBN). This biobehavioral study utilized a comparative design to prospectively evaluate the biological CCK response and the corresponding behavioral ratings of satiety and other eating-related sensations in individuals with BN (n=10), RBN (n =14), and healthy controls (CON, n=13). CCK and behavioral ratings were assessed at baseline, +15, +30, and +60 minutes following the ingestion of a standardized liquid test meal. The BN group's CCK response was blunted and approached significance (p =.052) when compared to the RBN and CON groups. As predicted the RBN and CON groups' CCK response did not significantly differ. This finding supports the premise that CCK may normalize following abstinence from binge and purge (vomit) episodes and that this is a state versus trait related phenomenon. A significant positive relationship between CCK response and ratings of satiety occurred in the RBN group only (r=.59, p<.05). A new and unanticipated finding in the BN group was a significant relationship (r=.86, p < .01, two-tailed) between their CCK response and urge to vomit. A greater urge to vomit was reported by those individuals who had increased CCK response. Therefore, it is unknown whether the normalization of CCK functioning is a protective or liability factor in the stabilization and recovery process. Replication studies utilizing a larger sample size are needed to understand the role of CCK in recovery and the subsequent development of novel treatment strategies for those suffering with BN. / Thesis (PhD) — Boston College, 2012. / Submitted to: Boston College. Connell School of Nursing. / Discipline: Nursing.

Background: Adolescent obesity has tripled over the last three decades and is associated with an 80 percent risk of adult obesity, hypertension, diabetes, hypercholesterolemia, and decreased life expectancy. Current adolescent obesity medical recommendations include bariatric surgery and appetite suppressants which lower BMI, but present serious health risks. Nutrition and exercise interventions promote health, however, meta-analysis reveal do not lower BMI. Mindful eating, a behavioral skill, reconnecting eating to satiety cues, and has potential as an anti-obesity intervention which lowers BMI, while promoting health. Study Aims: Aim 1: To determine the effect of a mindful eating intervention compared to usual diet and exercise information on BMI of obese female adolescents. Aim 2: To determine if the effect of a mindful eating intervention on BMI of obese female adolescents is sustained over time. Aim 3: To determine the feasibility of conducting a group mindful eating intervention over six weeks for obese adolescent girls in their school setting. Methods: Obesity was measured by Body Mass Index (BMI) = Weight in Pounds / Height in inches x Height in inches x 703. The sample included adolescent females aged 14-17 years with BMI>90th%. Participants were randomized to an intervention group receiving a 6 week mindful eating intervention and a comparison group receiving the usual care of nutrition and physical activity handouts. Participants' BMI was measured at baseline, immediately post intervention and at 4 week follow up assessing intervention effectiveness. Results: ANOVA results demonstrate a statistically significant difference in BMI between the experimental and comparison groups F(1,2)=22.24, p<.001. On average, the experimental group's BMI decreased 0.71, whereas the comparison group's BMI increased by 1.1 over the 6 week intervention. The experimental group's BMI continued to decline at the 4 week follow up. Attrition from the study was 38%, below the 45% set feasibility threshold. A group mindful eating intervention over six weeks for obese adolescent girls was effective in lowering BMI sustained over time is feasible. Teaching the behavioral skill of mindful eating holds great promise for combatting obesity in adolescents. Future study should include a school based intervention with a larger more diverse sample.

The hypothesis that consumption of whey protein (WP) prior to a meal suppresses short-term food intake and reduces post-meal glycemia by insulin-dependent and -independent mechanisms in healthy young adults was explored in three studies. Study one investigated the effect of solid vs. liquid forms of WP (50 g) and sucrose (75 g) on food intake at 1 h. Whey protein, whether in solid or liquid form, suppressed food intake more than sucrose. Study two examined the effect of WP (10-40 g) consumed 30 min prior to a meal on food intake, and pre- and post-meal blood concentrations of glucose and insulin. Whey protein reduced food intake and post-meal glycemia in a dose-dependent manner without increased blood insulin concentrations. In the third study, glycemic control after WP was compared with glucose, at doses of 10 and 20 g. Both pre-meal WP and glucose consumption reduced post-meal glycemia similarly. However, WP resulted in lower pre-meal blood glucose and delayed gastric emptying, lower pre-and post-meal and overall insulin secretion and concentrations and higher GLP-1 and PYY concentrations compared with glucose. Thus, the results of this research support the hypothesis that consumption of WP prior to a meal suppresses short-term food intake and reduces post-meal glycemia by insulin-dependent and -independent mechanisms in healthy young adults.

The hypothesis that consumption of whey protein (WP) prior to a meal suppresses short-term food intake and reduces post-meal glycemia by insulin-dependent and -independent mechanisms in healthy young adults was explored in three studies. Study one investigated the effect of solid vs. liquid forms of WP (50 g) and sucrose (75 g) on food intake at 1 h. Whey protein, whether in solid or liquid form, suppressed food intake more than sucrose. Study two examined the effect of WP (10-40 g) consumed 30 min prior to a meal on food intake, and pre- and post-meal blood concentrations of glucose and insulin. Whey protein reduced food intake and post-meal glycemia in a dose-dependent manner without increased blood insulin concentrations. In the third study, glycemic control after WP was compared with glucose, at doses of 10 and 20 g. Both pre-meal WP and glucose consumption reduced post-meal glycemia similarly. However, WP resulted in lower pre-meal blood glucose and delayed gastric emptying, lower pre-and post-meal and overall insulin secretion and concentrations and higher GLP-1 and PYY concentrations compared with glucose. Thus, the results of this research support the hypothesis that consumption of WP prior to a meal suppresses short-term food intake and reduces post-meal glycemia by insulin-dependent and -independent mechanisms in healthy young adults.

No description available.

Purpose: Indulgent parent feeding-styles have been associated with higher child body mass index (BMI); more direct influences on children's eating are not well characterized. This study examined whether African American (AA) children exhibited poorer appetite regulation when mothers had an indulgent feeding style relative to other feeding styles. This study also examined whether the FTO gene influenced the relationship between feeding style and appetite regulation. Methods: An observational design was used to evaluate the association of maternal feeding styles with child appetite among 100 obese and non-obese AA children aged 5-6 y. The Child Feeding Styles Questionnaire was used to categorize maternal feeding styles as authoritative, authoritarian, indulgent or uninvolved. Observed child satiation was measured at 4 laboratory-based dinner meals (portion sizes 100%, 150%, 200%, and 250% of those offered in reference condition). Change in energy intake across the 4 meals was estimated using a random slope mixed effects linear model. Parents' reports of child satiety responsiveness were assessed using the Child Eating Behavior Questionnaire. Child BMI percentile and BMI-for-age z-scores were calculated using measured height and weights. Generalized linear models were used to predict child appetite using parental feeding styles (covariates: gender, child BMI, maternal education, and income). The study center collected DNA and RNA through saliva samples from each child participant. Of the 100 children enrolled, 32 obese children and a random sample of 32 non-obese children were selected for genotyping and expression analysis. This resulted in the genotyping of three FTO gene SNPs, rs9939609, rs3751812 and rs8050136. FTO mRNA levels were measured using TaqMan Gene Expression Assays. Results: Children of indulgent feeders showed lower satiation compared to other children by consuming more energy as food portion sizes were systematically increased (p Conclusions: These findings provide new evidence that indulgent feeding-styles are associated with poorer appetite regulation among AA children. / Epidemiology

Background: Monosodium glutamate (MSG) imparts umami taste associated with proteins and is known to act as a flavor-enhancer. Several adult studies and a recent study of infants suggests that MSG may also have beneficial effects on appetite by promoting satiety. This research is the first to assess effects of MSG on perceived and objective satiety among children. Methods: A between-subjects design (MSG+ or MSG-) was used to evaluate the effect of adding MSG to a soup pre-load on subsequent satiety among children aged 7-9 years. Children were randomly assigned to experimental condition (MSG+ or MSG-). Perceived hunger and fullness were evaluated prior to and following consumption of the pre-load using a Visual Analogue Scale (VAS). Objective satiety was assessed using weighed food intake methods at an ad libitum meal following the preload. Results: Children in the MSG+ condition showed greater decreases in perceived hunger following the consumption of the pre-load than children in the MSG- condition (F=4.05, p&lt;0.05). Total energy intake at the ad libitum meal did not vary by MSG condition. Conclusions: The results of this study provide evidence that MSG may reduce perceived hunger among 7- to 9- year old children. / Public Health

This research examines the hypothesis that the satiety effect of cholecystokinin octapeptide (CCK-8) is mediated by changes in gastric emptying. A method for collection of gastric emptying data, the double sampling procedure, is developed and validated for use in the rat. The double sampling technique permits repeated measurements of liquid gastric volume and thus describes the time course of emptying within a single experimental session. Further, the method allows determination of the amount of gastric secretion, volume emptied into the intestines, and amount of gastric load remaining in the stomach. Experiments are presented which: i) demonstrate the utility of the technique; ii) validate its accuracy in determining gastric volume; iii) indicate the stability of measurements obtained with this procedure; and iv) provide a procedure for quantitative evaluation of data obtained with this technique. Using the double sampling procedure, the ability of CCK-8 to delay gastric emptying and to influence feeding are then compared under similar experimental conditions. The effect of CCK-8 on gastric emptying is assessed in 6 hr deprived rats receiving 10 ml intragastric test loads of either .15M saline or 15% sucrose. Intraperitoneal (ip) injections of CCK-8 in doses of 1.4-22.4 ug/kg produce a dose-dependent retardation of gastric emptying of both saline and nutrient. Lower doses of CCK-8, 0.01 and 0.1 ug/kg, have no effect on gastric emptying. The effect of CCK-8 on feeding is assessed in rats tested under the same experimental conditions used in the gastric emptying studies. Doses of CCK-8 capable of retarding gastric emptying also suppress eating in a dose-dependent manner. These findings provide necessary correlational support for the hypothesis that satiety produced by CCK-8 is mediated by inhibition of gastric emptying. However, a further quantitative analysis of the correspondence of the gastric emptying and feeding effects of CCK-8 suggest that retardation of emptying may not account for the entire satiety effect of the peptide. The next set of studies provide direct tests of whether changes in gastric emptying mediate CCK-induced satiety. If gastric emptying plays a significant role in the satiety produced by CCK-8 then: i) the effects of CCK-8 on emptying and feeding should share similar kinetics, and ii) peptides that inhibit emptying should also inhibit feeding. I show that CCK-8 (5.6 ug/kg) injected coincident with introduction of an intragastric load or presentation of a test meal produces a rapid inhibition of both emptying and feeding. In contrast, the identical dose of CCK-8 administered 15 min before testing causes no inhibition of emptying, even though the peptide retains its ability to produce satiety. I also test the abilities of the peptides pentagastrin (100 ug/kg), bombesin (8 & 16 ug/kg) and secretin (2.86, 14.3 & 28.6 ug/kg) to reduce food intake and inhibit gastric emptying. Pentagastrin does not affect food intake or gastric emptying. Bombesin causes a small transient delay in emptying but a large and sustained suppression of eating. High dose secretin (14.3 ug/kg) causes no significant reduction of food intake, even though this dose of secretin inhibits emptying to the same degree as 1.4 ug/kg CCK-8, which does reduce intake. Thus, although CCK-8 does influence the rate of gastric emptying, the present results indicate that the inhibition of emptying by CCK is neither necessary nor sufficient to explain its satiety effect. / Thesis / Doctor of Philosophy (PhD)

Two major aspects of CCK-induced satiety were examined in the food deprived sham-feeding rat: the kinetics of the inhibition of feeding produced by CCK and the interaction of CCK-induced satiety with oropharyngeal stimulation. Four results were presented regarding the kinetics of the CCK satiety effect. First, CCk administered coincident with the initiation of sham feeding inhibits feeding in a dose-related manner. Second, the increased efficacy of the higher dose of CCK delivered at the same time as sham feeding results from an increase in the size of maximum suppression and an increase in the time of suppression effected via a decreased latency to suppression. Third, CCk delivered 15 minutes before sham feeding begins has no effect on feeding. Fourth, the administration of a long-lasting derivative of CCK 15 minutes prior to the initiation of sham feeding can suppress intake. Two results were presented regarding the role of oropharyngeal stimulation in CCK-induced satiety. First, it was shown that oropharyngeal stimulation enhances the satiety action of CCK. Second, the amount and pattern of feeding inhibition produced by CCK are equivalent regardless of whether the peptide is administered coincident with, or some time after, the initiation of sham feeding. The implications of these results for the therapeutic use of this peptide and its role in producing satiety are discussed. / Thesis / Master of Arts (MA)

The worm Caenorhabditis elegans is a well-studied model organism in numerous aspects of its biology. This small free living nematode has less than 1,000 cells, but shows clear conservation in both signaling and behavior to mammals in aspects of appetite control. This is of importance to humans, where failure of appetite control is a major factor in the unprecedented obesity epidemic that we see today. In general, worm behavior reflects its internal nutritional state and the availability and quality of food. Specifically, worms show a behavioral state that mimics aspects of the mammalian behavioral satiety sequence, which has been termed satiety quiescence. We have used locomotion tracking and Hidden Markov Model analysis to identify worm behavioral state over time, finding quiescence along with the established worm locomotive behaviors roaming and dwelling. Using this analysis as well as more conventional cell biology and genetic approaches we have further investigated satiety signaling pathways. We have found that the neuron ASI is a major center of integration of signals regarding the internal nutritional state of the worms as well as the nutritional content of its environment. Our results show that cGMP causes levels of the TGFβ ligand to be increased in fasted worms, which is then released and binds to its receptor on the RIM and RIC neurons. This signaling connects nutritional state to behavioral response, promoting the sleep-like behavioral state satiety quiescence. Additionally, we have begun a candidate approach examining several other groups of signaling molecules for potential roles in satiety quiescence signaling including cannabinoids, multidrug resistance proteins, and neuropeptides. The result of this investigation is a better understanding of mechanisms of satiety quiescence signaling as well as a new tool that provides highly quantitative, unbiased, and automated data to aid in our ongoing work.