BAGNASCO, MICHELA, MICHAEL G. DUBE, ADI KATZ, PUSHPA S. KALRA, AND SATYA P. KALRA. Leptin expression in hypothalamic PVN reverses dietary obesity and hyperinsulinemia but stimulates ghrelin. Obes Res. 2003;11:1463-1470. Objective: In order to circumvent the multiple peripheral effects of hyperleptinemia and leptin resistance, the efficacy of leptin transgene expression in the hypothalamic paraventricular nucleus (PVN) to reinstate the central energy homeostasis in obesity was examined.
Research Methods and Procedures:A recombinant adenoassociated viral vector encoding either leptin (rAAV-lep) or green fluorescent protein (rAAV-GFP) was microinjected into the PVN of obesity-prone rats consuming a high-fat diet (HFD). Results: rAAV-lep, and not rAAV-GFP, microinjection significantly reduced energy intake and enhanced energy expenditure, thereby resulting in normalization of weight and blood levels of leptin, insulin, free fatty acids, and glucose concomitant with enhanced ghrelin secretion during the extended period of observation. Discussion: Thus, we show, for the first time, that amelioration of leptin insufficiency with enhanced localized leptin availability in the PVN alone can reverse dietary obesity and the attendant hyperinsulinemia and concurrently block the central stimulatory effects of elevated endogenous ghrelin on food intake and adiposity.
Approximately half of both New York state claims and court cases involved death or devastating morbidity, mostly related to airway complications, resulting in large awards. Tonsillectomy is a source of uncommon but potentially high-dollar-value litigation exposure to the surgeon, often attributable to non-surgical complications.
All species exhibit critical period for sensory development, yet very little is known about the molecules involved in the changes in the network wiring that underlies this process. Here the role of brain-derived neurotrophic factor (BDNF) in the critical period of thermal control establishment in chicks was investigated.Neuroanatomically, the body temperature is balanced by the preoptic anterior hypothalamus (PO/AH) and controlled by thermosensitive neurons. Exposure to hot or cold conditions during the critical period of temperature control development causes a plastic change in the ratio between heat-and cold-sensitive cells and can modulate temperature tolerance.It was found that expression of BDNF mRNA but not of NGF or neurotrophin-3 was induced in the PO/AH of 3-d-old chicks during both heat and cold exposure. The peak of BDNF induction in both heat and cold exposure occurred after 6 h, with, respectively, threefold and sevenfold increases in its mRNA expression.To prove the concept that BDNF activation is a critical step in thermal-experience-dependent plasticity, BDNF was "knocked down" using antisense. It was found that, when BDNF in the PO/AH was inhibited by 80% during the third postnatal day, thermal establishment was impaired, and, after 1 week, the chicks' body temperature was reduced by 0.5°C. Furthermore, later in life, their reaction to thermal challenge was altered, and they exhibited a pronounced reduction in their ability to maintain their body temperature and body weight under harsh conditions. Together, these results prove that BDNF is critically involved in thermal-experience-dependent development.
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