Bioenergetic and Metabolic Consequences of the Loss of Gonadal Function

性腺功能丧失的生物能和代谢后果

• 批准号: 8344030
• 负责人: Wendy M Kohrt
• 金额: $ 108.53万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-20 至 2017-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8344030
• 关键词: Bioenergetic; Metabolic; Consequences; Loss; Gonadal

DESCRIPTION (provided by applicant): The overarching objective of the University Of Colorado Anschutz Medical Campus Specialized Center Of Research on Sex Differences (UCAMC SCOR) is to develop an interdisciplinary and translational research program to advance the understanding of the Bioenergetic and Metabolic Consequences of the Loss of Gonadal Function. There is compelling evidence from studies of laboratory animals that gonadectomy causes a dramatic decrease of 30-80% in spontaneous physical activity in males and females. Even more intriguing is the observation that this results in excess weight gain, a marked increase in visceral fat, and metabolic dysfunction in female animals but not males. If such findings are relevant to humans, the age related decline in gonadal function may be an important independent determinant of disease risk. Moreover, this would be expected to have a greater adverse effect on the health of women than men, because the loss of gonadal function occurs at an earlier age in women. There will be three SCOR Research Projects to advance novel research in this area: 1) Project I (clinical): Bioenergetic and Metabolic Consequences of the Loss of Ovarian Function in Women (PI: W Kohrt); 2) Project II (preclinical): Effects of Pre-existing Obesity on Consequences of the Loss of Ovarian Function (PI: P MacLean); and 3) Project III (basic): Sex Hormones Differentially Regulate Production of Distinct Adipocyte Populations (PI: D Klemm). The Administrative Core will contribute to the success of the SCOR by: 1) providing scientific leadership for a focused translational and transdisciplinary research program on the consequences of the loss of gonadal function; 2) monitoring the productivity of SCOR Research Projects; 3) expanding the scope of the SCOR through an Ancillary Projects program; 4) expanding the cadre of investigators conducting research on the gonadal regulation of energy balance and metabolism through the Ancillary Projects program; 5) integrating activities of the SCOR with closely partnered programs at UCAMC, including the Center on Aging, the BIRCWH, the Center for Women's Health Research, the Nutrition and Obesity Research Center, the Women's Reproductive Health Research Career Development program, and the Colorado Clinical and Translational Science Institute; 6) providing biostatistical and data management support for the SCOR research projects; and 7) providing administrative support for financial oversight, regulatory oversight, and scheduling and general management of SCOR activities. PUBLIC HEALTH RELEVANCE: The SCOR is closely aligned with the 2 required overarching themes: 1) all 3 projects address sex/gender determinants because they investigate biological effects of the loss of gonadal function that impact heath; and 2) the SCOR is interdisciplinary, as evidenced by the focus on the regulation of the lineage of adipocytes in mice (Project III), to the impact of local estradiol production on fat and muscle metabolism in rats (Project II), to the effect of the loss of gonadal function on physical activity and energy balance in women (Project I).

描述（由申请人提供）：科罗拉多大学安舒茨医学院性别差异研究专业中心（UCAMC SCOR）的总体目标是开发一个跨学科和翻译研究计划，以促进对性腺功能丧失的生物能量和代谢后果的理解。实验室动物研究中有令人信服的证据表明，性腺切除术导致雄性和雌性自发性体力活动急剧减少30-80%。更有趣的是观察到，这导致雌性动物体重过度增加，内脏脂肪显著增加，代谢功能障碍，而不是雄性。如果这些发现与人类相关，那么与年龄相关的性腺功能下降可能是疾病风险的重要独立决定因素。此外，预计这对女性健康的不利影响比男性更大，因为女性性腺功能的丧失发生在较早的年龄。将有三个SCOR研究项目，以推进这一领域的新研究：1）项目I（临床）：女性卵巢功能丧失的生物能量和代谢后果（PI：W Kohrt）; 2）项目II（临床前）：既存肥胖对卵巢功能丧失后果的影响（PI：P MacLean）;和3）项目III（基础）：性激素差异调节不同脂肪细胞群体的产生（PI：D Klemm）。行政核心将通过以下方式为SCOR的成功做出贡献：1）为关于性腺功能丧失后果的重点转化和跨学科研究计划提供科学领导; 2）监控SCOR研究项目的生产力; 3）通过辅助项目计划扩大SCOR的范围; 4）通过辅助项目计划，扩大研究人员队伍，对能量平衡和代谢的性腺调节进行研究; 5）将SCOR的活动与UCAMC的密切合作项目相结合，包括老龄化中心，BIRCWH，妇女健康研究中心，营养和肥胖研究中心，妇女生殖健康研究职业发展计划和科罗拉多临床和转化科学研究所; 6）提供生物统计和数据 为SCOR研究项目提供管理支持;以及7）为SCOR活动的财务监督、监管监督、时间安排和一般管理提供行政支持。 公共卫生相关性：SCOR与2个所需的总体主题密切一致：1）所有3个项目都涉及性/性别决定因素，因为它们调查了影响健康的性腺功能丧失的生物学效应; 2）SCOR是跨学科的，因为 通过对小鼠脂肪细胞谱系调节的关注（项目III）证明， 从局部雌二醇产生对大鼠脂肪和肌肉代谢的影响（项目II）到性腺功能丧失对妇女体力活动和能量平衡的影响（项目I）。