Dissertation
Central monoaminergic pathways in appetite regulation
University of Iowa
Doctor of Philosophy (PhD), University of Iowa
Summer 2023
DOI: 10.25820/etd.006890
Abstract
Obesity is a major health and economic concern worldwide. It decreases life quality and increases mortality rate. The high risk of mortality is linked to life-threatening comorbidities such as cardiovascular disease and oncologic diseases. It is estimated that almost 1 in 2 people will be obese by 2030. While there are new promising pharmaceutical treatments that have recently hit the market, these treatments have varying levels of efficacy in patients. Thus, it is crucial to understand the underlying causes of obesity. Sustained overconsumption of high calorie food leads to positive energy balance which promotes obesity. Most of the current therapeutic agents used to combat obesity work by reducing appetite, which highlights the importance of understanding how the brain controls feeding. In the central nervous system (CNS), there are many molecules and cell types that regulate food intake. This thesis is mainly focused on the role of monoaminergic neural pathways in appetite regulation. The first part of this dissertation will focus on serotonin, a well-known anorectic molecule produced by the dorsal raphe nucleus (DRN). Through this work, we demonstrate that DRNSERTforebrain circuits regulate satiety. Second, we examine novel appetite regulation in a unique brain region called the nucleus solitary tract (NTS). The NTS is a crucial hub transferring gustatory and endocrine signals from the periphery to the brain. Our work reveals that NTS catecholaminergic (CA) neurons project to the paraventricular hypothalamic nucleus (PVN) to regulate appetite control. Anterior NTSCAPVN increases appetite, while posterior NTSCAPVN causes satiety. Also, stimulation of posterior NTSCAPVN pathway shows anxiety-like behavior. The last section of this dissertation will examine the central control of feeding time. To accomplish this, we focus primarily on agouti-related peptide (AgRP) neurons which are known as “hunger neurons.” We reveal that rhythmic AgRP neuronal activation partially mimics food entrainment. Also, we examined the effect of opioidergic signaling onto AgRP neurons and found that activation of mu opioid receptor directly decreases AgRP neuronal activity which may lead to satiety.
Overall, my thesis work reveals unique neural pathways that regulate appetite which may be helpful for future drug developments to combat obesity and eating disorders.
Details
- Title: Subtitle
- Central monoaminergic pathways in appetite regulation
- Creators
- Iltan Aklan
- Contributors
- Matthew Potthoff (Advisor)Rory A Fisher (Committee Member)Kamal Rahmouni (Committee Member)Catherine Marcinkiewcz (Committee Member)Jon Resch (Committee Member)
- Resource Type
- Dissertation
- Degree Awarded
- Doctor of Philosophy (PhD), University of Iowa
- Degree in
- Pharmacology
- Date degree season
- Summer 2023
- Publisher
- University of Iowa
- DOI
- 10.25820/etd.006890
- Number of pages
- xix, 148 pages
- Copyright
- Copyright 2023 Iltan Aklan
- Language
- English
- Date submitted
- 07/20/2023
- Description illustrations
- color illustrations, color maps
- Description bibliographic
- Includes bibliographical references (pages 131-148).
- Public Abstract (ETD)
Obesity is a major economic and health problem worldwide. The number of overweight or obese people is increasing significantly every year. Based on current estimations, by 2030, 1 in 2 people will be obese. That is why it is crucial to understand the underlying reasons of obesity. Clearly, obesity represents a state of energy in balance such that energy consumed is greater than energy expended. Currently, there are treatments available for obesity, but the degree of efficacy in patients is variable. While most patients lose some degree of weight with these treatments, there are still patients that fail to respond to these drugs. Notably, these drugs mostly primarily by decreasing appetite. Thus, it is important to understand the mechanisms that control feeding to develop new therapeutic options. Here, we reveal new brain regions that regulate feeding. These findings provide new insights which may guide new pharmacological modalities to combat obesity.
- Academic Unit
- Neuroscience and Pharmacology
- Record Identifier
- 9984454540602771
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