The Role of the Cannabinoid Receptor Type 1 in Energy Balance, Glucose Metabolism, and Thermogenesis
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University of Cincinnati / OhioLINK
2013
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ndltd-OhioLink-oai-etd.ohiolink.edu-ucin13679447452021-08-03T05:23:24Z The Role of the Cannabinoid Receptor Type 1 in Energy Balance, Glucose Metabolism, and Thermogenesis Bajzer, Matej Neurology Obesity cannabinoids CB1 Metabolism diabetes Brown adipose tissue The endocannabinoid system (ECS) is composed of the cannabinoid receptors 1 and 2 (CB1 and CB2), their lipid derived ligands, and their biosynthetic and degradative enzymes. The ECS is distributed widely throughout the body and has been implicated in many aspects of neurophysiology, however in recent years CB1 has been especially noted for its role in modulating energy balance and glucose homeostasis. Selective CB1 antagonists (SR141716 or rimonabant) developed as anti-obesity agents were successful at decreasing body weight, however, due to adverse psychiatric effects, were removed from the market. In order to facilitate better targeting of future anti-obesity agents it is critical to understand the mechanisms by which CB1 antagonists promote weight loss. In this work we investigate the physiologic role of the ECS in energy balance and glucose metabolism. In chapter 1 we will discuss the chemical structure of cannabinoids, as well as the central and peripheral functions of the ECS especially as it relates to brown adipose tissue and the defense of body weight. In chapter 2 we will assess whether CB1 receptors are implicated in the physiological defense of body weight. We will test the hypothesis that CB1 antagonism, rather than being obligatorily anorectic, changes food intake downward or upward depending on the level of adiposity in DIO mice. We also show that attenuation of anorexia during chronic CB1 antagonism is not due to the development of drug tolerance; rather it is due to the mice achieving their new, decreased, defended body weight. In chapter 3 we will evaluate the physiologic mechanisms by which CB1 antagonism improves glucose metabolism and insulin sensitivity independent of food-intake and weight-loss, as well as the effects of CB1 antagonism on brown adipose tissue (BAT) function. Our studies demonstrate that chronic CB1 antagonism markedly enhances insulin-mediated glucose utilization in DIO mice, independent of its anorectic and weight-reducing effects as well as activates the BAT, in a manner that is dependent on SNS innervation. Taken together these studies describe an important role for the ECS in determining the level of body adiposity that the brain will maintain and defend, furthermore we demonstrate that both anorexia and BAT thermogenesis associated with CB1 antagonism are adiposity dependent phenomena. Finally we report that CB1 antagonism increases glucose utilization and has a potent effect on insulin-stimulated BAT glucose uptake; these findings reveal a novel role for CB1 receptors as regulators of glucose metabolism. 2013-09-17 English text University of Cincinnati / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=ucin1367944745 http://rave.ohiolink.edu/etdc/view?acc_num=ucin1367944745 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws. |
| collection |
NDLTD |
| language |
English |
| sources |
NDLTD |
| topic |
Neurology Obesity cannabinoids CB1 Metabolism diabetes Brown adipose tissue |
| spellingShingle |
Neurology Obesity cannabinoids CB1 Metabolism diabetes Brown adipose tissue Bajzer, Matej The Role of the Cannabinoid Receptor Type 1 in Energy Balance, Glucose Metabolism, and Thermogenesis |
| author |
Bajzer, Matej |
| author_facet |
Bajzer, Matej |
| author_sort |
Bajzer, Matej |
| title |
The Role of the Cannabinoid Receptor Type 1 in Energy Balance, Glucose Metabolism, and Thermogenesis |
| title_short |
The Role of the Cannabinoid Receptor Type 1 in Energy Balance, Glucose Metabolism, and Thermogenesis |
| title_full |
The Role of the Cannabinoid Receptor Type 1 in Energy Balance, Glucose Metabolism, and Thermogenesis |
| title_fullStr |
The Role of the Cannabinoid Receptor Type 1 in Energy Balance, Glucose Metabolism, and Thermogenesis |
| title_full_unstemmed |
The Role of the Cannabinoid Receptor Type 1 in Energy Balance, Glucose Metabolism, and Thermogenesis |
| title_sort |
role of the cannabinoid receptor type 1 in energy balance, glucose metabolism, and thermogenesis |
| publisher |
University of Cincinnati / OhioLINK |
| publishDate |
2013 |
| url |
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1367944745 |
| work_keys_str_mv |
AT bajzermatej theroleofthecannabinoidreceptortype1inenergybalanceglucosemetabolismandthermogenesis AT bajzermatej roleofthecannabinoidreceptortype1inenergybalanceglucosemetabolismandthermogenesis |
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