UCLA

Obesity is a growing problem both in The United States and world-wide and women in The United States have the highest mean body mass index (BMI) of high-income countries. Brain imaging studies have provided great insights in the interplay between the gut and the brain in regulation of human ingestive behavior, allowing for the exploration of complex signaling in the brain related to appetite-stimulating cues. Obesity has been viewed as a disruption of the balance between homeostatic processing for energy needs and hedonic processing involved in the rewarding value of food, but these brain differences have yet to be fully examined when it comes to the brain’s resting state.

The primary aims of this dissertation were to explore the differences in homeostatic and hedonic brain networks in obese women using resting state techniques to compare frequency oscillations and functional connectivity with lean women at a baseline state and then to determine if functional connectivity would be altered by a variant of a known satiety hormone, GLP-1. In additional, to compare these brain abnormalities with behavioral measures related to appetite. This dissertation also includes a preliminary study examining the impact of high and low calorie beverages on hedonic and homeostatic networks of lean vs obese women while viewing pictures of food which pointed to key abnormalities of the obese woman’s brain and an obese-only discrepancy between brain activations and behavioral measures related to subjective feelings of fullness and appetite.

Our analyses at baseline indicated differences in hedonic regions for overweight and obese women, centering around a key region of reward, the nucleus accumbens which was shown to have an increase in grey matter volume as well as altered frequency distributions in the higher BMI group. Functional connectivity of the nucleus accumbens with other regions in the hedonic network was observed to be greater in the more obese group, a brain pattern also observed in many forms of addiction. Upon injection of the GLP-1 analog, Exenatide, functional connectivity was observed to increase more so in the obese group between key homeostatic regions centered around the Nucleus Tractus Solitaries (NTS). This drug-induced increase in functional connectivity was correlated with an increase of hunger in all subjects but more so in the obese. These results support the notion that Exenatide has an impact on brain connectivity, particularly in the obese and suggest the drug’s influence on appetite control might be linked to modified connectivity of an NTS-based network.