Browsing by Subject "Ventromedial Hypothalamic Nucleus"
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Item The Functional Roles of Steroidogenic Factor 1 in the Ventromedial Nucleus of the Hypothalamus(2009-06-17) Kim, Ki Woo; Parker, Keith L.Steroidogenic factor 1 (SF-1) is a nuclear receptor that plays important roles in the hypothalamic-pituitary-steroidogenic organ axis. Global knockout studies in mice revealed the essential in vivo roles of SF-1 in the ventromedial hypothalamic nucleus (VMH), adrenal glands, and gonads. One limitation of global SF-1 knockout mice is their early postnatal death from adrenocortical insufficiency. To overcome limitations of the global knockout mice and to delineate the roles of SF-1 in the brain, we used Cre/loxP recombination technology to genetically ablate SF-1 specifically in the central nervous system (CNS). Mice with CNS-specific knockout of SF-1 mediated by nestin-Cre showed increased anxiety-like behavior, revealing a crucial role of SF-1 in a complex behavioral phenotype. Our studies with CNS-specific SF-1 KO mice also defined roles of SF-1 in regulating the VMH expression of target genes implicated in anxiety and energy homeostasis. Therefore, present work will focus on the functional roles of SF-1 in the VMH linked to anxiety and energy homeostasis.Item Loss of Ventromedial Hypothalamic Leptin Receptors Results in Increased Adiposity and a Metabolic Syndrome(2008-05-12) Bingham, Nathan Christian; Parker, Keith L.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.