The Impact of GLP-1 Analog, Exenatide, on The Resting Brain of Lean vs Obese Women

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

The Impact of GLP-1 Analog, Exenatide, on The Resting Brain of Lean vs Obese Women

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

Influence of Sucrose Ingestion on Brainstem and Hypothalamic Intrinsic Oscillations in Lean and Obese Women

Background & aimsThe study of intrinsic fluctuations in the blood oxygen level-dependent signal of functional magnetic resonance imaging can provide insight into the effect of physiologic states on brain processes. In an effort to better understand the brain-gut communication induced by the absorption and metabolism of nutrients in healthy lean and obese individuals, we investigated whether ingestion of nutritive and non-nutritive sweetened beverages differentially engages the hypothalamus and brainstem vagal pathways in lean and obese women.MethodsIn a 2-day, double-blind crossover study, 11 lean and 11 obese healthy women underwent functional magnetic resonance imaging scans after ingestion of 2 beverages of different sucrose content, but identical sweetness. During scans, subjects rested with eyes closed.ResultsBlood oxygen level-dependent fluctuations demonstrated significantly greater power in the highest frequency band (slow-3: 0.073-0.198 Hz) after ingestion of high-sucrose compared with low-sucrose beverages in the nucleus tractus solitarius for both groups. Obese women had greater connectivity between the right lateral hypothalamus and a reward-related brain region and weaker connectivity with homeostasis and gustatory-related brain regions than lean women.ConclusionsIn a functional magnetic resonance imaging study, we observed sucrose-related changes in oscillatory dynamics of blood oxygen level-dependent fluctuations in brainstem and hypothalamus in lean and obese women. The observed frequency changes are consistent with a rapid vagally mediated mechanism due to nutrient absorption, rather than sweet taste receptor activation. These findings provide support for altered interaction between homeostatic and reward networks in obese individuals

Surgically Induced Changes in Gut Microbiome and Hedonic Eating as Related to Weight Loss

ObjectiveWeight loss surgery results in significant changes in the anatomy, function, and intraluminal environment of the gastrointestinal tract affecting the gut microbiome. Although bariatric surgery results in sustained weight loss, decreased appetite, and hedonic eating, it is unknown whether the surgery-induced alterations in gut microbiota play a role in the observed changes in hedonic eating. We explored the following hypotheses: (1) laparoscopic sleeve gastrectomy (LSG) results in changes in gut microbial composition; (2) alterations in gut microbiota are related to weight loss; (3) alterations in gut microbiome are associated with changes in appetite and hedonic eating.MethodsEight obese women underwent LSG. Their body mass index, body fat mass, food intake, hunger, hedonic eating scores, and stool samples were obtained at baseline and 1-month postsurgery. 16S ribosomal RNA gene sequencing was performed on stool samples. DESeq2 changes in microbial abundance. Multilevel-sparse partial least squares discriminant analysis was applied to genus-level abundance for discriminative microbial signatures.ResultsLSG resulted in significant reductions in body mass index, food intake, and hedonic eating. A microbial signature composed of five bacterial genera discriminated between pre- and postsurgery status. Several bacterial genera were significantly associated with weight loss (Bilophila, q = 3E-05; Faecalibacterium q = 4E-05), lower appetite (Enterococcus, q = 3E-05), and reduced hedonic eating (Akkermansia, q = .037) after surgery.ConclusionsIn this preliminary analysis, changes in gut microbial abundance discriminated between pre- and postoperative status. Alterations in gut microbiome were significantly associated with weight loss and with reduced hedonic eating after surgery; however, a larger sample is needed to confirm these findings

Influence of Sucrose Ingestion on Brainstem and Hypothalamic Intrinsic Oscillations in Lean and Obese Women

BACKGROUND & AIMS: The study of intrinsic fluctuations in the blood oxygen level-dependent signal of functional magnetic resonance imaging can provide insight into the effect of physiologic states on brain processes. In an effort to better understand the brain–gut communication induced by the absorption and metabolism of nutrients in healthy lean and obese individuals, we investigated whether ingestion of nutritive and non-nutritive sweetened beverages differentially engages the hypothalamus and brainstem vagal pathways in lean and obese women. METHODS: In a 2-day, double-blind crossover study, 11 lean and 11 obese healthy women underwent functional magnetic resonance imaging scans after ingestion of 2 beverages of different sucrose content, but identical sweetness. During scans, subjects rested with eyes closed. RESULTS: Blood oxygen level-dependent fluctuations demonstrated significantly greater power in the highest frequency band (slow-3: 0.073–0.198 Hz) after ingestion of high-sucrose compared with low-sucrose beverages in the nucleus tractus solitarius for both groups. Obese women had greater connectivity between the right lateral hypothalamus and a reward-related brain region and weaker connectivity with homeostasis and gustatory-related brain regions than lean women. CONCLUSIONS: In a functional magnetic resonance imaging study, we observed sucrose-related changes in oscillatory dynamics of blood oxygen level-dependent fluctuations in brainstem and hypothalamus in lean and obese women. The observed frequency changes are consistent with a rapid vagally mediated mechanism due to nutrient absorption, rather than sweet taste receptor activation. These findings provide support for altered interaction between homeostatic and reward networks in obese individuals