Obesity is a serious and growing public health problem in the United States and the world. While many overweight and obese individuals can lose weight, few can maintain weight loss for substantial periods of time. This suggests that physiological adaptations occur with weight loss that oppose further weight loss and promote weight regain. The weight reduced state is associated with alterations in meal-related hormone responses as well as long-term adiposity signals such as leptin both potentially promoting increased energy intake. While these signals may directly impact energy balance regulation, there is increasing evidence that these physiologic signals interact with reward, behavioral and cognitive systems to ultimately enhance food intake. For example, in normal weight individuals, there appear to be important interactions between environmental food-related cues and brain regions known to be important in the homeostatic regulation of food intake, and these interactions are affected by food intake and energy balance. These responses appear to be altered in obesity and more so following diet-induced weight loss which would favor increase food intake. This inability to properly adapt to the environment may represent an important mechanism for the difficulty of successful long-term weight loss maintenance. Successful weight loss maintenance interventions must, therefore, require control of energy balance via a complex interaction between physiologic and nonphysiologic systems, and understanding these mechanisms will allow for the potential development of new and/or better strategies for weight loss maintenance. Two such successful interventions are weight loss surgery and exercise. While both of these interventions have been shown to been associated with changes or 'normalization'in meal-related hormone responses that might favor reduced food intake, the mechanisms by which these interventions help promote weight loss and prevent weight regain are not well understood. Studies designed to elucidate the mechanisms of successful weight loss maintenance interventions such as these are a critical area for investigation. The overall goal of this proposal is to examine the effects of weight loss surgery and exercise on the neuronal, behavioral and hormonal response to a meal. It is hypothesized that these successful weight loss maintenance interventions will restore the normal neuronal response to a meal and that this improved neuronal response will be associated with changes in both meal associated hormones and appetite ratings. In order to examine these hypotheses we propose to use fMRI to examine the neuronal response to visual food cues before and after a meal as well as to study the hormonal response to a meal in individuals who have undergone Roux-en-Y gastric bypass or gastric banding as compared to diet control and in individuals maintaining weight loss through a supervised exercise intervention as compared to diet control.

Public Health Relevance

Obesity is a serious and growing public health problem in the United States and the world. While many overweight and obese individuals can lose weight, few can maintain weight loss for substantial periods of time. This suggests that adaptations occur with weight loss that oppose further weight loss and promote weight regain. The most successful interventions for sustained weight loss are bariatric surgery and exercise. It is unclear, however, how these interventions help individuals maintain a reduced body weight. By understanding the complex interactions between the brain response to eating and food cues and physiologic changes with these interventions we hope to be able to develop new strategies and/or interventions for sustained weight loss.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK089095-04
Application #
8538950
Study Section
Clinical and Integrative Diabetes and Obesity Study Section (CIDO)
Program Officer
Laughlin, Maren R
Project Start
2010-09-10
Project End
2014-08-31
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
4
Fiscal Year
2013
Total Cost
$396,530
Indirect Cost
$137,360
Name
University of Colorado Denver
Department
Psychiatry
Type
Schools of Medicine
DUNS #
041096314
City
Aurora
State
CO
Country
United States
Zip Code
80045
Legget, Kristina T; Cornier, Marc-Andre; Bessesen, Daniel H et al. (2018) Greater Reward-Related Neuronal Response to Hedonic Foods in Women Compared with Men. Obesity (Silver Spring) 26:362-367
Smucny, Jason; Wylie, Korey P; Kronberg, Eugene et al. (2017) Nicotinic modulation of salience network connectivity and centrality in schizophrenia. J Psychiatr Res 89:85-96
Legget, Kristina T; Wylie, Korey P; Cornier, Marc-Andre et al. (2016) Exercise-related changes in between-network connectivity in overweight/obese adults. Physiol Behav 158:60-7
Legget, Kristina T; Cornier, Marc-Andre; Rojas, Donald C et al. (2015) Harnessing the power of disgust: a randomized trial to reduce high-calorie food appeal through implicit priming. Am J Clin Nutr 102:249-55
Wylie, Korey P; Kronberg, Eugene; Maharajh, Keeran et al. (2015) Between-network connectivity occurs in brain regions lacking layer IV input. Neuroimage 116:50-8
Smucny, Jason; Visani, Adrienne; Tregellas, Jason R (2015) Could vagus nerve stimulation target hippocampal hyperactivity to improve cognition in schizophrenia? Front Psychiatry 6:43
Tregellas, Jason R; Smucny, Jason; Legget, Kristina T et al. (2015) Effects of a ketogenic diet on auditory gating in DBA/2 mice: A proof-of-concept study. Schizophr Res 169:351-354
McFadden, Kristina L; Tregellas, Jason R; Shott, Megan E et al. (2014) Reduced salience and default mode network activity in women with anorexia nervosa. J Psychiatry Neurosci 39:178-88
Tregellas, Jason R (2014) Neuroimaging biomarkers for early drug development in schizophrenia. Biol Psychiatry 76:111-9
McFadden, Kristina L; Cornier, Marc-Andre; Tregellas, Jason R (2014) The role of alpha-7 nicotinic receptors in food intake behaviors. Front Psychol 5:553

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