LOUISIANA COBRE: P4: MECHANISMS OF AGING-INDUCED LEPTIN RESISTANCE AND OBESITY

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 A.具体目标 具体目标1：验证衰老增强高脂饮食（HFD）对大脑瘦素信号传导、代谢和行为的负面影响的假设。 具体目标二：测试老化将损害动物在HFD停止后减少身体肥胖和恢复正常脑瘦素信号传导的能力的假设。 具体目标3：验证瘦素通过NRF 2信号增强抗氧化酶活性来保护下丘脑和海马神经元免受氧化应激的假设。 具体目标4：确定瘦素信号传导和海马和下丘脑区域内的氧化应激之间的功能相互作用。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. A. Specific Aims Specific Aim 1: Test the hypothesis that aging enhances the negative effects of high fat diet (HFD) on brain leptin signaling, metabolism and behavior. Specific Aim 2: Test the hypothesis that aging will impair the ability of the animal to reduce body adiposity and recover normal brain leptin signaling following cessation of a HFD. Specific Aim 3: Test the hypothesis that leptin protects against oxidative stress in hypothalamic and hippocampal neurons by enhancing antioxidant enzyme activity via NRF2 signaling. Specific Aim 4: Determine the functional interaction between leptin signaling and oxidative stress within areas of the hippocampus and hypothalamus.