Translational Analyses of Ingestive Behavior After Gastric Bypass

胃绕道手术后摄入行为的转化分析

• 批准号: 9922677
• 负责人: Alan C Spector
• 金额: $ 33.93万
• 依托单位: FLORIDA STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-05-01 至 2023-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9922677
• 关键词: Address; Affect; Animal Model; Appetitive Behavior; Attenuated; Behavior; Behavioral; Behavioral Mechanisms; Body Weight; Body Weight decreased; Cardiovascular system; Chronic; Clinical; Collaborations; Complement; Consumption; Desire for food; Development; Eating; Endocrine; Energy Intake; Experimental Designs; Fatty acid glycerol esters; Feeding Patterns; Feeding behaviors; Food; Food Aversion; Food Patterns; Food Preferences; Food Selections; GLP-I receptor; Gastric Bypass; Glycemic Index; Hormones; Human; Ingestion; Intake; International; Intervention; Ireland; Lead; Learning; Liquid substance; Maintenance; Malignant Neoplasms; Measures; Modeling; Morbid Obesity; Motivation; Non-Insulin-Dependent Diabetes Mellitus; Nutrient; Obesity; Octreotide; Operative Surgical Procedures; Outcome; Palate; Patient Self-Report; Patients; Pattern; Peptides; Peripheral; Pharmacology; Physiological; Process; Publishing; Rattus; Research; Rodent; Role; Satiation; Services; Signal Transduction; Sucrose; Taste Perception; Taste aversion; Testing; Therapeutic Intervention; Vegetables; Visceral; Weight maintenance regimen; Work; analog; base; behavior change; design; experience; experimental study; feeding; food avoidance; glucagon-like peptide 1; glycemic control; improved; insight; mortality; neural circuit; obesity management; programs; public health relevance; reduced food intake; research and development; response; somatostatin analog; sugar; virtual

 DESCRIPTION (provided by applicant): After Roux-en-Y gastric bypass (RYGB), patients decrease: appetite, caloric intake, body weight, and glycemia, all of which are maintained long-term. This is a large reason why it has become a popular treatment for morbid obesity and Type 2 diabetes mellitus (T2DM). However, a major unresolved issue is whether, after RYGB, patients choose to eat less foods that are high in fat and sugar in favor of lower energy dense alternatives such as vegetables. If true, this could conceivably contribute to improved body weight and glycemia. Disparities among studies on food selection and intake are likely due to the almost complete reliance on self- reported food intake which is vulnerable to inaccuracy. This controversy can best be resolved by complementing existing findings with direct measures of target behaviors in humans that can also be applied to animal models and vice-versa. The proposed experiments will extend the published and preliminary findings suggesting that RYGB alters food preferences without ostensibly changing food palatability. Such changes in food selection alone have been postulated to benefit patients with obesity and/or T2DM and this may be an under-investigated means by which RYGB improves maintenance of body weight and glycemic control. Direct measures in both rats and humans after RYGB will be used to test the hypothesis that the selection and intake of foods varying in fat content and glycemic index, as well as the pattern of ingestion within and across meals, changes in a manner that leads to beneficial outcomes on body weight. While the apparent progressive changes in food preference after RYGB in the rat model strongly suggest learning, such experience-based changes could be driven by either food aversion (changed palatability) or food avoidance (unchanged palatability). Evidence disambiguating these learning processes is lacking, and the proposed experiments are designed to explicitly distinguish between these important and conceptually distinct behavioral mechanisms. The exaggerated pleiotropic gut hormone response to RYGB has been the most promising lead to a physiologic mechanism underlying the changes in feeding, weight loss, and glycemic control. One gut hormone in particular, glucagon like peptide-1 (GLP-1) has been a target in pharmacological interventions in the management of T2DM and is implicated in feeding satiation. Accordingly, the somatostatin analogue Octreotide will be used to block the pleiotropic gut hormone response to RYGB in translational experiments to interrogate the role of these endocrine processes in the progressive changes in ingestive behavior observed. In other experiments, the GLP-1 receptor will be selectively targeted by the antagonist Exendin-9. This scientific alliance is made possible through the US-Ireland R&D Partnership Program which is allowing this established international research team to continue to apply their complementary expertise in the service of addressing fundamental questions that can help guide future research in the treatment and management of obesity and T2DM.

 描述（由申请人提供）：在roux-en-y胃旁路（RYGB）之后，患者减少：食欲，热量摄入量，体重和血糖，所有这些都长期保持。这是为什么它已成为病态肥胖症和2型糖尿病（T2DM）的流行疗法的重要原因。但是，一个尚未解决的主要问题是，在RYGB之后，患者是否选择少脂肪和糖的食物较少，而倾向于较低的能量致密替代品，例如蔬菜。如果是真的，这可能会导致体重和血糖的改善。关于食物选择和摄入量的研究之间的差异可能是由于对自我报告的食物摄入几乎完全缓解，这很容易受到不准确的影响。通过直接衡量人类目标行为的现有发现，可以最好地解决这一争议，这些发现也可以应用于动物模型，反之亦然。拟议的实验将扩展出已发表的初步发现，表明RYGB改变了食物的偏好，而不会表面上改变食物的可口性。仅发布食物选择的这种变化就可以使肥胖症和/或T2DM患者受益，这可能是一种投资不足的含义，RYGB可以改善体重和血糖控制的维持。 RYGB后大鼠和人类的直接措施将用于检验以下假设：脂肪含量和血糖指数的选择和摄入量以及饮食中和整个餐食中的摄入模式都会变化，以一种方式变化，从而导致体重对体重的有益成果。虽然大鼠模型中RYGB后食物偏好的明显渐进变化强烈建议学习，但这种基于经验的变化可能是由于食物厌恶（可口的性能变化）或避免食物（不变的可口性）驱动。缺乏歧义这些学习过程的证据，所提出的实验旨在明确区分这些重要和概念上不同的行为机制。夸张的多效性肠马对RYGB的反应一直是喂养，体重减轻和血糖控制变化的生理机制的最有希望的导致。尤其是一种肠马，像胡椒1（GLP-1）这样的胰高血糖素一直是T2DM治疗的药理干预措施的目标，并且暗示在喂养疾病中。根据生长抑素模拟，将使用在翻译实验中阻止对Rygb的多效性肠龙反应，以询问这些内分泌过程在观察到的摄入行为的渐进变化中的作用。在其他实验中，GLP-1接收器将被拮抗剂Exendin-9选择。通过美国 - 爱尔兰研发伙伴计划使这一科学联盟成为可能，该计划允许该既定的国际研究团队继续将其完整的专业知识应用于解决基本问题的服务，以帮助指导未来的肥胖和管理研究研究研究。

项目成果

Meal Patterns and Food Choices of Female Rats Fed a Cafeteria-Style Diet Are Altered by Gastric Bypass Surgery.

• DOI: 10.3390/nu13113856
• 发表时间: 2021-10-28
• 期刊: Nutrients
• 影响因子: 5.9
• 作者: Blonde GD;Price RK;le Roux CW;Spector AC
• 通讯作者: Spector AC

A new apparatus to analyze meal-related ingestive behaviors in rats fed a complex multi-food diet.

• DOI: 10.1016/j.physbeh.2022.113824
• 发表时间: 2022-08-01
• 期刊: Physiology & behavior
• 影响因子: 2.9
• 作者: Blonde GD;Fletcher FH;Tang T;Newsome R;Spector AC
• 通讯作者: Spector AC

Evaluation of the impact of gastric bypass surgery on eating behaviour using objective methodologies under residential conditions: Rationale and study protocol.

• DOI: 10.1016/j.conctc.2021.100846
• 发表时间: 2021-12
• 期刊: Contemporary clinical trials communications
• 影响因子: 1.5
• 作者: Redpath T;Naseer F;Price RK;Boyd A;Martin M;le Roux CW;Spector AC;Livingstone MBE
• 通讯作者: Livingstone MBE

A Comparison of Total Food Intake at a Personalised Buffet in People with Obesity, before and 24 Months after Roux-en-Y-Gastric Bypass Surgery.

• DOI: 10.3390/nu13113873
• 发表时间: 2021-10-29
• 期刊: Nutrients
• 影响因子: 5.9
• 作者: Kapoor N;Al Najim W;Menezes C;Price RK;O'Boyle C;Bodnar Z;Spector AC;Docherty NG;le Roux CW
• 通讯作者: le Roux CW

Methodological issues in assessing change in dietary intake and appetite following gastric bypass surgery: A systematic review.

• DOI: 10.1111/obr.13202
• 发表时间: 2021-06
• 期刊: Obesity reviews : an official journal of the International Association for the Study of Obesity
• 作者: Redpath TL;Livingstone MBE;Dunne AA;Boyd A;le Roux CW;Spector AC;Price RK
• 通讯作者: Price RK