Loss of Ventromedial Hypothalamic Leptin Receptors Results in Increased Adiposity and a Metabolic Syndrome
| dc.contributor.advisor | Parker, Keith L. | en |
| dc.creator | Bingham, Nathan Christian | en |
| dc.date.accessioned | 2010-07-12T17:51:35Z | |
| dc.date.available | 2010-07-12T17:51:35Z | |
| dc.date.issued | 2008-05-12 | |
| dc.description.abstract | Obesity is a leading health problem here in the United States and in other developing countries. Obesity is a risk factor for several life-threatening conditions including Type II diabetes, hypertension, and cardiovascular disease. Given the growing obesity epidemic, understanding the mechanisms whereby the central nervous system monitors and regulates energy homeostasis has become a major focus of scientific research in the last several decades. The discovery that mice fed a low fat diet exhibit significantly increased adipose mass with no difference in weight compared to wild-type littermates. Further, these mice exhibit a metabolic syndrome including mild steatosis, dyslipidemia, and hyperleptinemia. From a young age, Lepr KOleptin, an adipocyte-derived hormone, acts on the brain to suppress appetite and stimulate energy expenditure greatly extended our understanding of such mechanisms. The leptin receptor is expressed in a number of hypothalamic nuclei known to play a role in energy homeostasis. While much work has focused on leptin's actions in the arcuate nucleus, other sites have received substantially less attention. Here, I report that mice lacking leptin receptors within the ventromedial hypothalamic nucleus (Lepr KOVMH) develop increased adiposity and a metabolic syndrome. Lepr KOVMH mice fed high fat rodent chow show an increased sensitivity to diet-induced obesity, while Lepr KOVMH mice are hyperinsulinemic and eventually become glucose intolerant. These data demonstrate that Lepr KOVMH mice are a novel genetic model of obesity and may be used for the study of energy partitioning, lipogenesis, and central leptin signaling. | en |
| dc.format.digitalOrigin | born digital | en |
| dc.format.medium | Electronic | en |
| dc.format.mimetype | application/pdf | en |
| dc.identifier.oclc | 421114695 | |
| dc.identifier.uri | https://hdl.handle.net/2152.5/384 | |
| dc.language.iso | en | en |
| dc.subject | Mice | en |
| dc.subject | Receptors, Leptin | en |
| dc.subject | Adiposity | en |
| dc.subject | Ventromedial Hypothalamic Nucleus | en |
| dc.title | Loss of Ventromedial Hypothalamic Leptin Receptors Results in Increased Adiposity and a Metabolic Syndrome | en |
| dc.type | Thesis | en |
| dc.type.genre | dissertation | en |
| dc.type.material | Text | en |
| thesis.date.available | 2008-05-12 | |
| thesis.degree.department | Graduate School of Biomedical Sciences | en |
| thesis.degree.discipline | Integrative Biology | en |
| thesis.degree.grantor | UT Southwestern Medical Center | en |
| thesis.degree.level | Doctoral | en |
| thesis.degree.name | Doctor of Philosophy | en |