Epigenetic regulation of adipose tissue distribution in women

女性脂肪组织分布的表观遗传调控

• 批准号: 9306064
• 负责人: Timothy F Osborne
• 金额: $ 61.38万
• 依托单位: ADVENTHEALTH ORLANDO
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-06-28 至 2020-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9306064
• 关键词: Abdomen; Address; Adipocytes; Adipose tissue; Adult; American; Androgens; Animals; Apple; Blood Vessels; Cardiovascular Diseases; Cardiovascular system; Cells; Cellular biology; Central obesity; Chromatin Structure; Chronic Disease; Clinical; Complex; Coupled; Cultured Cells; Data; Development; Diabetes Mellitus; Drug or chemical Tissue Distribution; Endocrine; Epigenetic Process; Epinephrine; Estrogens; Event; Exhibits; Fatty acid glycerol esters; Female; Gene Cluster; Gene Expression; Gene Expression Profile; Genes; Goals; Growth; Health; Histones; Human; Hydrocortisone; Hypertension; Hypoxia; In Vitro; Insulin Resistance; Investigation; KDM1A gene; Knowledge; Laboratories; Lead; Literature; Maps; Messenger RNA; Metabolic; Metabolic Diseases; MicroRNAs; Molecular; Molecular Profiling; Myocardial Infarction; Nuclear; Obesity; Pattern; Pear; Phenotype; Play; Process; Puberty; Publishing; Regulation; Regulator Genes; Risk; Risk Factors; Shapes; Signal Transduction; Somatotropin; Somatotype; Stroke; Testing; Thigh structure; Untranslated RNA; Visceral; Waist-Hip Ratio; Weight; Woman; adipokines; differential expression; disorder risk; epidemiologic data; epigenetic regulation; experimental study; gene repression; genome-wide; high risk; improved; in vivo; inter-individual variation; knock-down; lipid biosynthesis; lipid disorder; lipid metabolism; men; overexpression; prevent; protective effect; public health relevance; response; sex; sexual dimorphism; subcutaneous

 DESCRIPTION (provided by applicant): In 1954 Vague identified central adiposity as a key determinant of several common chronic diseases including diabetes, myocardial infarction, hypertension and stroke. Vague contrasted the 'apple' pattern with metabolically beneficial gluteal - femoral adipose tissue (pears). This observation spawned more than a half century of clinical and laboratory investigation yet, there is still a major gap in our knowledge regarding th molecular underpinnings of adipose tissue patterning. It is clear that the relationship between adiposity and cardiovascular and diabetes disease risk is tightly related to fat patterning (apple vs. pear). In this regard, obese women who have a preponderance of abdominal subcutaneous fat (apple-shaped) have a higher risk of developing insulin resistance, diabetes and CVD relative to women who carry their excess weight in gluteal/thigh adipose tissue (pear-shaped). This proposal addresses the fundamental mechanisms associated with depot specific adipose function directly in humans. Our preliminary published and new unpublished studies support the hypothesis that fat depot specific gene expression and associated epigenetic signatures are maintained when abdominal vs. gluteal pre-adipocytes are cultured in vitro. The proposed new experiments will extend these studies to reveal genome-wide differences in epigenetic marks in adipose tissue and adipocytes from both men and women. We will also investigate the different gene expression patterns and associated epigenetic marks that define the pear vs. apple body type of the American adult female. We will uncover new fundamental molecular signatures and processes that are relevant to development of insulin resistance, diabetes and cardiovascular disease.

 描述（由申请人提供）：1954年，Vague将中心性肥胖确定为几种常见慢性疾病（包括糖尿病、心肌梗死、高血压和中风）的关键决定因素。Vague将“苹果型”与代谢有益的臀股脂肪组织（梨型）进行了对比。这一观察结果催生了超过半个世纪的临床和实验室研究，然而，在我们关于脂肪组织模式化的分子基础的知识方面仍然存在重大差距。很明显，肥胖与心血管和糖尿病风险之间的关系与脂肪模式（苹果与梨）密切相关。在这方面，相对于臀部/大腿脂肪组织（梨形）超重的女性，腹部皮下脂肪（苹果形）占优势的肥胖女性患胰岛素抵抗、糖尿病和心血管疾病的风险更高。）。该提议解决了与直接在人类中的贮库特异性脂肪功能相关的基本机制。我们的初步发表和新的未发表的研究支持这一假设，即当体外培养腹部与臀部前脂肪细胞时，脂肪库特异性基因表达和相关的表观遗传特征得以维持。拟议中的新实验将扩展这些研究，以揭示男性和女性脂肪组织和脂肪细胞中表观遗传标记的全基因组差异。我们还将研究不同的基因表达模式和相关的表观遗传标记，定义梨与苹果的身体类型的美国成年女性。我们将发现与胰岛素抵抗、糖尿病和心血管疾病发展相关的新的基本分子特征和过程。