The endocannabinoid system, consisting of the CB1R and lipid derived endogenous cannabinoid molecules, has been shown to significantly contribute to the development of diabetes and obesity. Although CB1R inverse agonists are effective at improving insulin sensitivity and protecting against diet induced obesity, these drugs have severe side effects associated with the widespread distribution of CB1Rs in the CNS and the periphery. The goal of this application is to investigate the role of CB1Rs in the SF1 neurons of the ventromedial hypothalamus to regulate energy homeostasis. We will also examine if this subset of neurons is responsible for the metabolic improvements associated with CB1R inverse agonists. We anticipate the results from our investigation will provide novel insight to the development of effective therapies to combat metabolic disease while circumventing potential side effects.

Public Health Relevance

The endogenous cannabinoid system is a key regulator of whole body energy balance. Activation of this system contributes to the development of diabetes and obesity, whereas drugs that block the cannabinoid system can protect from diabetes and obesity. While effective, these drugs also have severe side effects. We believe that the cannabinoid system in a small subset of neurons regulates energy and glucose balance. Studying these neurons will aid in the development of novel therapies, without side effects, to better treat or prevent diabetes and obesity

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK100659-07
Application #
10091429
Study Section
Integrative Physiology of Obesity and Diabetes Study Section (IPOD)
Program Officer
Cooke, Brad
Project Start
2014-07-08
Project End
2023-01-31
Budget Start
2021-02-01
Budget End
2022-01-31
Support Year
7
Fiscal Year
2021
Total Cost
Indirect Cost
Name
University of Texas Sw Medical Center Dallas
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
800771545
City
Dallas
State
TX
Country
United States
Zip Code
75390
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