Characterization of Endogenous Nucleobindin-2/Nesfatin-1 in Rodents
| dc.contributor.advisor | local.embargo.terms | |
| dc.contributor.committeeMember | Unniappan, Suraj | |
| dc.contributor.committeeMember | Machin, Karen | |
| dc.contributor.committeeMember | Forsyth, George | |
| dc.contributor.committeeMember | Hiebert, Linda | |
| dc.contributor.committeeMember | Desai, Kaushik | |
| dc.contributor.committeeMember | Chelikani, Prasanth | |
| dc.creator | Mohan, Haneesha 1987- | |
| dc.date.accessioned | 2020-02-11T21:16:17Z | |
| dc.date.available | 2021-08-17T06:05:08Z | |
| dc.date.created | 2015-05 | |
| dc.date.issued | 2015-05-20 | |
| dc.date.submitted | May 2015 | |
| dc.date.updated | 2020-02-11T21:16:17Z | |
| dc.description.abstract | Whole body energy homeostasis is regulated by the endocrine system. Nesfatin-1 is a newly identified multifunctional metabolic peptide with insulinotropic, endocrine, glucoregulatory, fat reducing and cardiovascular functions. While nesfatin-1 tissue expression and secretion are considered meal responsive, it is unknown whether macronutrients and/or development regulate its secretion. Is endogenous nesfatin-1 critical for energy balance? The central hypothesis of this thesis research is that the tissue specific expression of NUCB2/nesfatin-1 is regulated developmentally, and by nutrients, and that endogenous NUCB2/nesfatin-1 is critical for the maintenance of energy homeostasis. The specific objectives of this research were to determine the developmental, and nutrient regulated expression of NUCB2/nesfatin-1, and to characterize the metabolic phenotype of mice lacking NUCB2/nesfatin-1. Three key findings were made in this research. First, it was found that NUCB2/nesfatin-1 presents an ontogenic pattern of expression in the gastroenteropancreatic tissues and serum of rats. An age-dependent co-expression of related peptides, ghrelin and its processing enzyme, ghrelin-O-acyl transferase (GOAT), and nesfatin-1 processing prohormone convertases were also found in the endocrine pancreas. Second, it was determined that the NUCB2 mRNA expression and NUCB2/nesfatin-1 secretion in mice are influenced by nutrients in a tissue specific manner in vitro and in vivo, and it depends on the duration of exposure to specific diets tested. This research identified nutrients as major regulators of endogenous NUCB2/nesfatin-1. Third, a sexually dimorphic effect of NUCB2/nesfatin-1 disruption in mice was found, with alterations in body weight, food intake, insulin secretion, glucose homeostasis and energy homeostasis. These data support a metabolic role for endogenous nesfatin-1. Together, this research provides important new information on developmental and cell specific regulation of nesfatin-1 expression, nutrient modulation of its expression and secretion, and an essential role for endogenous nesfatin-1 in maintaining energy homeostasis. For example, endocrine pancreas is an abundant source of nesfatin-1. Absence of endogenous nesfatin-1 causes defects in insulin secretion from islet beta cells, and alters glucose homeostasis. Exogenous nesfatin-1 causes a reduction in body weight. NUCB2 gene disruption resulted in abnormal body weight in mice, further confirming that nesfatin-1 indeed influences body mass. | |
| dc.format.mimetype | application/pdf | |
| dc.identifier.uri | http://hdl.handle.net/10388/12641 | |
| dc.subject | Nucleobindin-2, Nesfatin-1, Development, Nutrients, Metabolism, Energy Balance | |
| dc.title | Characterization of Endogenous Nucleobindin-2/Nesfatin-1 in Rodents | |
| dc.type | Thesis | |
| dc.type.material | text | |
| local.embargo.terms | 2021-08-17 | |
| thesis.degree.department | Veterinary Biomedical Sciences | |
| thesis.degree.discipline | Veterinary Biomedical Sciences | |
| thesis.degree.grantor | University of Saskatchewan | |
| thesis.degree.level | Doctoral | |
| thesis.degree.name | Doctor of Philosophy (Ph.D.) |