Obesity-associated diseases such as diabetes and cardiovascular disease together account for the leading cause of death in the United States. Roughly one-third of the U.S. population is obese, and it is estimated that nearly half of the population will be obese within the next two decades. To date, studies investigating the neural contribution to body weight control have focused largely on neuropeptidergic signaling in the hypothalamus, a key brain region involved in feeding behavior. However, signaling from extra-hypothalamic brain regions has also been implicated in regulating nutrient metabolism, appetite, and satiety. We recently uncovered a novel mechanism by which cholinergic signaling in the basal forebrain strongly influences body weight control. This discovery provides intriguing evidence that specific cholinergic signaling pathways in the brain critically regulate feeding behavior and body weight homeostasis. To elucidate the mechanisms by which forebrain cholinergic signaling influences body weight management, feeding behaviors, and metabolism, we will test the hypothesis that cholinergic signaling modulates metabolic and appetitive programs to regulate body weight. Using a combination conditional genetic targeting, optogenetic manipulations, electrophysiology, and behavioral analysis, we will set out to determine the role for basal forebrain cholinergic signaling in body weight control and obesity.

Public Health Relevance

We recently uncovered a novel role for cholinergic signaling in body weight control. This project focuses on elucidating the cholinergic mechanisms and synaptic connectivity that contributes to obesity and body weight control. Knowledge gained from these studies will provide needed insight into how cholinergic circuits in the central nervous system modulate metabolic and appetitive programs to regulate body weight.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
1R01DK109934-01
Application #
9152383
Study Section
Molecular Neurogenetics Study Section (MNG)
Program Officer
Stoeckel, Luke
Project Start
2016-07-15
Project End
2020-06-30
Budget Start
2016-07-15
Budget End
2017-06-30
Support Year
1
Fiscal Year
2016
Total Cost
$367,325
Indirect Cost
$112,756
Name
Baylor College of Medicine
Department
Genetics
Type
Schools of Medicine
DUNS #
051113330
City
Houston
State
TX
Country
United States
Zip Code
77030
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