Hypothalamus and adipose tissue are essential central and peripheral sites regulating energy homeostasis. Disruption of energy homeostasis can lead to diseases like anorexia and obesity in humans and reduced productivity in animals. Therefore, integrating knowledge in hypothalamic appetite regulation and adipose tissue metabolism is essential to maintain homeostasis. The aim of this dissertation was to elucidate molecular and cellular mechanisms of energy homeostasis in birds. We determined adipose tissue physiological changes during the first two weeks post-hatch in chickens from lines selected for low (LWS) and high (HWS) body weight. LWS was more dependent on yolk and subcutaneous fat mobilization for growth from hatch to day 4 post-hatch, with hyperplasia-predominated replenishment of the reservoir. In contrast, HWS was more dependent on feed for growth and maintained depot mass through hyperplasia and hypertrophy. From day 4 to 14 post-hatch, compared to maintenance of depot weight and adipocyte size in LWS, HWS accumulated clavicular and abdominal fat with minimal lipolysis. There was greater expression of precursor and proliferation markers in LWS with more apoptotic cells in the abdominal stromal vascular fraction on day 14 post-hatch, suggesting that apoptosis contributed to lower adipogenic potential and lack of abdominal fat in LWS. Exposure to thermal and nutritional stressors at hatch impaired growth by reducing yolk utilization and lowering body weight, lean and fat masses in LWS. Stress exposure resulted in increased global DNA methylation and DNA methyltransferase activity in the arcuate nucleus of the hypothalamus in LWS. Moreover, there was decreased binding to methyl-CpG-binding domain protein 2 in the promoter of corticotropin-releasing factor (CRF) because of hypomethylation in one CpG site at its core binding site in stressed LWS, which explains the increased CRF expression in the paraventricular nucleus of the hypothalamus. We next determined effects of nutritional status on adipose tissue physiology in Japanese quail, a less-intensively selected avian species. Six-hour fasting promoted lipolysis and gene expression changes in 7-day old quail with some changes restored to original levels within 1 hour of refeeding. Overall, our results reveal novel cellular and molecular mechanisms regulating appetite and adiposity in birds early post-hatch. / Doctor of Philosophy / Hypothalamus and adipose tissue are essential for regulating energy homeostasis in central and peripheral body sites, respectively. Disruption of energy homeostasis can lead to diseases like anorexia and obesity in humans and reduced productivity in animals. Therefore, integrating knowledge in hypothalamic appetite regulation and adipose tissue metabolism is essential to maintain energy homeostasis in both humans and animals. The aim of this dissertation was to elucidate molecular and cellular mechanisms of energy homeostasis in birds. We first determined adipose tissue physiological changes in chickens during the first two weeks post-hatch from lines selected for low (LWS) and high (HWS) body weight. These chickens have been selected for juvenile body weight for over 60 generations. The LWS are lean and anorexic, while HWS eat compulsively and develop obesity and metabolic syndrome. Such characteristics make the body weight line chickens good animal models to study physiological changes under anorexia and obesity. We found that LWS was more dependent on yolk reserves and subcutaneous fat mobilization for growth from hatch to day 4 post-hatch, with replenishment of the fat reservoir by increases in cell number. By contrast, HWS was more dependent on feed for growth and maintained depot mass through increased cell number and cell size. From day 4 to 14 post-hatch, HWS accumulated fat throughout the body, with less fat breakdown as compared to LWS. There was greater expression of cellular precursor and proliferation markers in LWS, with more dying cells in their abdominal fat on day 14 post-hatch, suggesting that programmed cell death is responsible for the lack of fat cell development in LWS. Exposure to thermal and nutritional stressors at hatch impaired growth by reducing yolk utilization and lowering body weight, lean and fat masses in LWS. There were many molecular changes in the hypothalamus, including changes in DNA that led to increased activation of corticotropin-releasing factor (CRF), a signaling molecule that is known to regulate the body's stress and appetite responses. Stress exposure increased global DNA methylation and DNA methyltransferase activity in the arcuate nucleus of the hypothalamus in LWS. Moreover, there was less methylation at the core binding site of methyl-CpG-binding domain protein 2 (MBD2), a protein that binds to methylated DNA to repress gene expression, in the CRF gene, in stressed LWS. In response to stress, there was decreased binding of MBD2 to the promoter region of CRF, which may explain increased expression of CRF in the paraventricular nucleus of LWS. These results demonstrate that early-life stressful events can cause epigenetic changes (like DNA methylation) that lead to alterations in physiology and behavior that persist to later in life. We next determined effects of nutritional status on adipose tissue physiology in Japanese quail, which have undergone less artificial selection than chickens and are more representative of a wilder-type bird. Six-hour fasting promoted lipolysis and gene expression changes in 7-day old quail with some changes restored to original levels within 1 hour of refeeding. Overall, our results provide novel perspectives on cellular and molecular mechanisms regulating appetite and adiposity in birds during early post-hatch development.
| Identifer | oai:union.ndltd.org:VTETD/oai:vtechworks.lib.vt.edu:10919/97584 |
| Date | 09 April 2020 |
| Creators | Xiao, Yang |
| Contributors | Animal and Poultry Sciences, Gilbert, Elizabeth R., Siegel, Paul B., Johnson, Sally E., Cline, Mark A., Liu, Dongmin |
| Publisher | Virginia Tech |
| Source Sets | Virginia Tech Theses and Dissertation |
| Detected Language | English |
| Type | Dissertation |
| Format | ETD, application/pdf, application/vnd.openxmlformats-officedocument.wordprocessingml.document |
| Rights | In Copyright, http://rightsstatements.org/vocab/InC/1.0/ |
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