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Anschutz大学医学校园的性别差异研究中心（UCAMC SCOR）的总体目标是制定跨学科和转化研究计划，以促进对GONADAL功能丧失的生物能源和代谢后果的理解。从实验动物的研究中，有令人信服的证据表明，男性和女性的自发性体育锻炼会导致30-80％的性腺切除术急剧下降。更有趣的是，观察到这会导致体重增加过多，内脏脂肪显着增加以及女性动物的代谢功能障碍，而不是雄性。如果这些发现与人类有关，则性腺功能与年龄相关的下降可能是疾病风险的重要独立决定因素。此外，预计这会对女性的健康产生比男性更大的不利影响，因为性腺功能的丧失发生在女性的早期。将有三个SCOR研究项目来推进该领域的新研究：1）I（临床）：女性卵巢功能丧失的生物能和代谢后果（PI：W KOHRT）； 2）II（临床前）：肥胖对卵巢功能丧失后果的影响（PI：P Maclean）； 3）项目III（基本）：性激素对不同脂肪细胞种群的产生（PI：D KLEMM）差异化。行政核心将通过以下方面的成绩为SCOR的成功做出贡献：1）为针对性的转化和跨学科研究计划提供科学领导力，以实现性腺功能丧失的后果； 2）监视SCOR研究项目的生产率； 3）通过辅助项目计划扩大SCOP的范围； 4）通过辅助项目计划扩大有关能量平衡和代谢的性腺调节研究的研究人员的干部； 5）将SCOR的活动与UCAMC紧密合作的计划相结合，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以及科罗拉多州的临床和翻译科学研究所； 6）提供生物统计和数据 对SCOR研究项目的管理支持； 7）为财务监督，监管监督以及SCOR活动的日程安排和一般管理提供行政支持。 公共卫生相关性：SCOR与所需的2个总体主题紧密一致：1）所有3个项目涉及性别/性别决定因素，因为它们研究了影响Heath的性腺功能丧失的生物学影响； 2）SCOR是跨学科的 对小鼠（项目III）中脂肪细胞谱系的调节的重点是证明 局部雌二醇产生对大鼠脂肪和肌肉代谢的影响（项目II）对性腺功能丧失对女性体育锻炼和能量平衡的影响（项目I）。