The role of BRCA1 in regulation of lipid metabolism in skeletal muscle

BRCA1在骨骼肌脂质代谢调节中的作用

• 批准号: 8286172
• 负责人: ESPEN E SPANGENBURG
• 金额: $ 15.97万
• 依托单位: UNIV OF MARYLAND, COLLEGE PARK
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-06-20 至 2014-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8286172
• 关键词: Ablation; Acetyl-CoA Carboxylase; Acute; Address; Animals; BRCA1 gene; Binding; Central obesity; Clinical; Complementary DNA; Coupled; Data; Development; Electroporation; Endocrine disruption; Estrogen Therapy; Estrogens; Exercise; Exhibits; Fatty acid glycerol esters; Female; Genetic; Glucose; Goals; Health; In Vitro; Intervention; Knowledge; Lead; Life; Lipids; Mammary Gland Parenchyma; Measures; Mediating; Menopause; Metabolic; Metabolic Diseases; Metabolic syndrome; Metformin; Mitochondria; Modality; Modeling; Mus; Muscle; Mutation; Obesity; Operative Surgical Procedures; Ovarian hormone; Ovariectomy; Ovary; Palmitates; Pattern; Phenotype; Phosphorylation; Physiological; Play; Postmenopause; Publishing; Regulation; Respiration; Risk; Role; Signal Transduction; Skeletal Muscle; Symptoms; Time; Visceral; Woman; Women' s Health; design; early onset; gain of function; in vivo; lipid metabolism; loss of function; malignant breast neoplasm; meetings; mouse model; novel; oxidized lipid; response

DESCRIPTION (provided by applicant): Menopause begins in the fifth decade of life and results in decreased circulating estrogens which coincides with increases in visceral fat mass placing women at elevated risk for the developing the metabolic syndrome. With the release of the Women's Health Initiative doctors have to reconsider current options for treating postmenopausal women. It is increasingly important to understand the physiological consequences of the loss of ovarian hormones (i.e. estrogens) on women's health so new interventions can be developed. Our data indicate that ovariectomized animals (OVX) exhibit symptoms of the metabolic syndrome, including increased visceral fat, impaired glucose dynamics and high circulating levels of lipid. We believe these changes in the OVX mice are due to a reduced ability of the skeletal muscle to effectively oxidize lipid, which we hypothesize is mediated in part by the gene breast cancer early onset 1 (BRCA1). This study will delineate the role of BRCA1 in regulating lipid entry into the mitochondria of skeletal muscle and attempt to determine if decreases in BRCA1 expression contribute to increased abdominal obesity in the OVX model.

描述（由申请人提供）：更年期开始于生命的第五个十年，导致循环雌激素减少，这与内脏脂肪量增加相一致，使女性患代谢综合征的风险增加。随着妇女健康倡议的发布，医生不得不重新考虑目前治疗绝经后妇女的选择。了解卵巢激素（即雌激素）损失对女性健康的生理后果越来越重要，因此可以开发新的干预措施。我们的数据表明，卵巢切除动物（OVX）表现出代谢综合征的症状，包括内脏脂肪增加，葡萄糖动力学受损和高循环水平的脂质。我们认为OVX小鼠的这些变化是由于骨骼肌有效氧化脂质的能力降低，我们假设这部分是由乳腺癌早发基因1（BRCA 1）介导的。本研究将描述BRCA1在调节脂质进入骨骼肌线粒体中的作用，并试图确定BRCA1表达的减少是否有助于OVX模型中腹部肥胖的增加。

项目成果

Mitochondrial oxygen consumption deficits in skeletal muscle isolated from an Alzheimer's disease-relevant murine model.

• DOI: 10.1186/1471-2202-15-24
• 发表时间: 2014-02-13
• 期刊: BMC neuroscience
• 影响因子: 2.4
• 作者: Schuh RA;Jackson KC;Schlappal AE;Spangenburg EE;Ward CW;Park JH;Dugger N;Shi GL;Fishman PS
• 通讯作者: Fishman PS