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Hypothalamic-Striatal Control of Motivation for Obesogenic Food

下丘脑-纹状体对致胖食物动机的控制

基本信息

批准号：
10027208
负责人：
Jonathan Dean Hommel
金额：
$ 1.03万
依托单位：
UNIVERSITY OF TEXAS MED BR GALVESTON
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-02-01 至 2021-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10027208
关键词：
Adult Affect Agonist Attenuated Automobile Driving Behavior Behavioral Behavioral Research Biology Brain Brain region Cardiovascular Diseases Chronic Consumption Corpus striatum structure DNQX DRD2 gene Data Diabetes Mellitus Dimensions Disease Eating Etiology Excitatory Amino Acid Antagonists Fatty acid glycerol esters Feeding behaviors Female Food Glutamate Agonist Glutamate Receptor Glutamates Health High Fat Diet Hypothalamic structure Individual Intake Label Lasers Lead Life Light Link Malignant Neoplasms Mediating Metabolic Metabolic syndrome Methodology Methods Microscopy Midbrain structure Motivation Neurobiology Neuromodulator Neurons Neuropharmacology Neurotransmitters Nucleus Accumbens Nutritional Obesity Obesity Epidemic Outcome Study Palate Pathway interactions Pharmacogenetics Physiological Play Population Psychological reinforcement Public Health RNA Rattus Regulation Research Project Grants Rewards Risk Rodent Rodent Model Role Synapses Techniques Testing Training Treatment outcome United States Viral addiction comorbidity cost design druggable target experimental study feeding food craving genetic manipulation genetic technology glutamatergic signaling hedonic improved in vivo knock-down male motivated behavior neural circuit neurobiological mechanism novel novel strategies obesogenic paraventricular nucleus pleasure pre-clinical presynaptic reward circuitry small hairpin RNA social transcriptome sequencing transmission process

项目摘要

PROJECT ABSTRACT Obesity is an alarming chronic health crisis that currently affects 39.8% of the adult population (2015-2016) in the United States. Obese individuals present a challenging public health problem because they are at increased risk for several life-threatening and costly co-morbidities including diabetes, metabolic syndrome, cardiovascular disease, and cancer. Because the financial and health burdens of obesity are so pernicious, a more mechanistic appreciation of the feeding behavior(s) that contribute to obesity is critical to understanding the etiology of this disease and for identifying druggable targets. One feeding behavior that contributes to obesity is overconsumption of highly palatable food. Highly palatable food, including high-fat food, is an important driver of obesity and has demonstrated reinforcement value in rodents. Reinforcement is mediated in part by the nucleus accumbens shell (NAcSh), a key neuroanatomical substrate that regulates hedonic feeding. Another substrate governing food intake is the paraventricular nucleus of the hypothalamus (PVN). The PVN regulates food intake at the level of physiological energy requirements, and facilitates homeostatic feeding behavior. PVN neurons project to the NAcSh (PVN→NAcSh) and orchestrate social reward, but their role in motivation for high-fat food remains unknown. Preliminary data indicate that the neurotransmitter Glutamate (Glu) plays an integral role in PVN→NAcSh transmission. Pharmacogenetic stimulation of PVN→NAcSh neurons results in robust and sustained presynaptic Glu release in the NAcSh. Additionally, administration of Glu agonists directly to the NAcSh decrease feeding, while administration of Glu antagonists evoke an immediate and sustained increase in consumption behavior. Despite considerable evidence of Glu involvement in consumption behavior, the role of Glu in motivation for high fat food has not been explored. We propose that Glu signaling within PVN→NAcSh neurons is a critical neuromodulator of motivation for high-fat food. The objectives of this proposal are to (1) establish the neuroanatomical basis for Glu signaling in PVN→NAcSh and (2) manipulate presynaptic Glu release in PVN→NAcSh to test specific hypotheses concerning the role of Glu in the regulation of motivation for high-fat food. Completion of these objectives will provide the applicant with training in new concepts and methodologies, including the neurobiology of obesity, the design and interpretation of behavioral experiments, principles and methods of neuropharmacology, and the application of genetic technology. The outcomes of these studies will have a sustained, powerful impact on our field by identifying a key regulatory role for Glu transmission in PVN→NAcSh mediated motivation for highfat food, which will critically advance efforts to improve treatment outcomes in obesity and metabolic dysregulation.

项目摘要

项目成果

期刊论文数量（3）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Highly Conserved Molecular Features in IgLONs Contrast Their Distinct Structural and Biological Outcomes.

DOI：
10.1016/j.jmb.2020.07.014
发表时间：
2020-09-04
期刊：
Journal of molecular biology
影响因子：
5.6
作者：
Venkannagari H;Kasper JM;Misra A;Rush SA;Fan S;Lee H;Sun H;Seshadrinathan S;Machius M;Hommel JD;Rudenko G
通讯作者：
Rudenko G

Combined nicotinamide N-methyltransferase inhibition and reduced-calorie diet normalizes body composition and enhances metabolic benefits in obese mice.

DOI：
10.1038/s41598-021-85051-6
发表时间：
2021-03-11
期刊：
Scientific reports
影响因子：
4.6
作者：
Sampson CM;Dimet AL;Neelakantan H;Ogunseye KO;Stevenson HL;Hommel JD;Watowich SJ
通讯作者：
Watowich SJ

Neurocognitive and developmental perspectives of obesity.

肥胖的神经认知和发育观点。