Cross sensitization of diet and alcohol on binge behaviors and metabolic dysfunction

饮食和酒精对暴饮暴食行为和代谢功能障碍的交叉敏感性

基本信息

批准号：
10670928
负责人：
Yuval Silberman
金额：
$ 34万
依托单位：
PENNSYLVANIA STATE UNIV HERSHEY MED CTR
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-01 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10670928
关键词：
Acute Alcohol abuse Alcohol consumption Alcoholism Alcohols Amygdaloid structure Animal Model Animal Testing Animals Behavior Behavioral Behavioral Model Brain region Cell Nucleus Cell physiology Cells Characteristics Chronic Chronic Disease Clinical Research Consumption Data Development Diet Disease Disease Progression Eating Electrophysiology (science)Ethanol Fatty acid glycerol esters Food Genetic Glucose Goals Health High Fat Diet Human Human Resources Hyperglycemia Impairment Insulin Insulin Resistance Intake Laboratories Link Mediating Mental Health Metabolic Metabolic dysfunction Metabolism Methods Mission Modeling Mus Neuroimmune Neurons Neurosciences Non-Insulin-Dependent Diabetes Mellitus Obese Mice Obesity Outcome Pancreas Pattern Physiology Population Positioning Attribute Prediabetes syndrome Predisposition Reporting Research Rewards Risk Reduction Rodent Signal Transduction Site Symptoms Synapses Techniques Testing United States Vagus nerve structure Work alcohol effect alcohol use disorder binge drinking binge type behavior blood glucose regulation brain cell comorbidity diet-induced obesity dorsal motor nucleus driving force epidemiology study glucose metabolism glutamatergic signaling heuristics improved insight interest mouse model neural neural circuit neuroinflammation neuromechanism neurotransmission novel obesity risk optogenetics patch clamp postsynaptic tool

项目摘要

Project Summary/Abstract Obesity and alcoholism are two of the most prevalent chronic diseases in the United States. These two diseases may be linked as obesity and alcoholism share common behavioral characteristics, such as binge intake, and are thought to utilize overlapping neural mechanisms. Additionally, obesity and alcoholism promote deficits in insulin and glucose metabolism, early predictors of Type II diabetes. The goal of this project is to understand how diets high in fat may interact with alcohol to worsen development and progression of both alcoholism and diet-induced obesity related metabolic dysfunction in mouse models. Specifically, we will examine how eating patterns can produce binge-type high fat diet food intake that may cross-sensitize to binge alcohol consumption in a novel behavioral model of co-morbid diet and ethanol interactions in mice. We will then examine the neurocircuitry involved in these binge intake patterns and determine the mechanisms by which high fat diets and alcohol modulate critical brain cell populations. Based on our preliminary data, we propose that high fat diet and alcohol consumption increase neuronal activation in the central nucleus of the amygdala via modulation of neuroimmune cell function. Finally, we will examine the impact of co-morbid high fat diet and alcohol consumption on insulin and glucose function and metabolism. In doing so, we will determine the mechanisms by which key neurocircuitry involved in the central control on insulin release are altered by high fat diet and alcohol. Specifically, we will be examining the mechanisms by which high fat diet and alcohol consumption inhibit the activity of neuronal populations in the dorsal motor nucleus of the vagus nerve that project to the pancreas and how this cell population is modulated by central amygdala inputs. These research questions will be tested with a novel combination of electrophysiologic, immunohistochemical, opto- and chemo- genetic, behavioral, and whole-animal physiology methods not typically seen within a single application and examine diet and alcohol changes from the cellular level to whole animal function. These studies will be of significant interest to the mission of the National Institute of Alcohol Abuse and Alcoholism, and are of important relevance to FOA PA-17-211. Successful completion of these studies will provide new understanding of the mechanisms involved in the disease progression of obesity and alcoholism as well as uncover new potential targets for the treatment of both disorders, both singularly and in co-morbid situations.

项目摘要/摘要肥胖和酒精中毒是美国最普遍的慢性疾病之一。这两种疾病可能是因为肥胖和酒精中毒具有共同的行为特征，例如暴饮暴食和被认为利用重叠的神经机制。此外，肥胖和酒精中毒会促进缺陷胰岛素和葡萄糖代谢，II型糖尿病的早期预测因子。该项目的目的是了解高脂肪的饮食如何与酒精相互作用，以使酒精中毒的发展和进展恶化饮食诱导的小鼠模型中与肥胖相关的代谢功能障碍。具体来说，我们将研究如何饮食图案可以产生暴饮暴食的高脂饮食食物摄入在小鼠合并饮食和乙醇相互作用的新型行为模型中的消耗。然后我们会检查这些暴饮暴食模式所涉及的神经记录，并确定该机制高脂肪饮食和酒精调节关键的脑细胞群体。根据我们的初步数据，我们建议高脂肪饮食和饮酒会增加杏仁核中央核中的神经元激活通过调节神经免疫细胞功能。最后，我们将研究合并高脂饮食的影响以及胰岛素和葡萄糖功能和代谢的饮酒。这样，我们将确定胰岛素释放中心控制中涉及的关键神经记录的机制被高改变脂肪饮食和酒精。具体而言，我们将研究高脂饮食和酒精的机制消费抑制神经元种群在迷走神经背运动核中的活性投影到胰腺，以及该细胞种群如何由中央杏仁核输入调节。这些研究问题将通过电生理，免疫组织化学，光学和光学生理学结合进行测试化学遗传，行为和全动物生理学方法通常在单个中未见应用和检查饮食和酒精从细胞水平变为整个动物功能。这些国家酗酒和酒精中毒研究所的使命将引起研究的重大兴趣，与FOA PA-17-211具有重要意义。这些研究的成功完成将提供新的了解肥胖和酗酒疾病进展的机制以及发现新的潜在靶标，用于对两种疾病的治疗，无论是在合并的情况下。

项目成果

期刊论文数量（2）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Access schedules mediate the impact of high fat diet on ethanol intake and insulin and glucose function in mice.

DOI：
10.1016/j.alcohol.2020.03.007
发表时间：
2020-08
期刊：
Alcohol (Fayetteville, N.Y.)
影响因子：
0
作者：
Coker CR;Aguilar EA;Snyder AE;Bingaman SS;Graziane NM;Browning KN;Arnold AC;Silberman Y
通讯作者：
Silberman Y

Subregional Differences in Alcohol Modulation of Central Amygdala Neurocircuitry.