Epigenetic Control of Adipogenesis

脂肪生成的表观遗传控制

• 批准号: 7934528
• 负责人: ANTHONY N IMBALZANO
• 金额: $ 36.53万
• 依托单位: UNIV OF MASSACHUSETTS MED SCH WORCESTER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-20 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7934528
• 关键词: ATP Hydrolysis; Address; Adipocytes; Adipose tissue; Adopted; Affect; Arginine; Attention; Basic Science; Biochemical; Biological; Cells; Chromatin; Chromatin Structure; Complement; Coupled; DNA; DNA Binding; Development; Diabetes Mellitus; Enzymes; Epigenetic Process; Evaluation; Event; Follow-Up Studies; Future; Gene Activation; Gene Expression; Gene-Modified; Genes; Genomics; Goals; Health; Health Care Costs; Histones; Individual; Investigation; Kinetics; Lead; Life Style; Lipids; Malignant Neoplasms; Mediating; Methylation; Molecular; Obesity; Obesity associated disease; Overweight; Pathway interactions; Physiological Processes; Population; Post-Translational Protein Processing; Protein-Arginine N-Methyltransferase; Proteins; Publishing; Regulator Genes; Social Problems; Specific qualifier value; Staging; Therapeutic Intervention; Tissues; Training; Transcription Regulatory Protein; United States; Weight Gain; arginine methyltransferase; cell growth; cell type; chromatin remodeling; cost; design; improved; in vivo; lipid biosynthesis; metaplastic cell transformation; myogenesis; obesity treatment; productivity loss; programs; small molecule; transcription factor

Obesity and health complications related to obesity, including diabetes, impact a significant proportion of the population in the United States, and projections indicate that the number of obese and overweight individuals will continue to rise in the future. The costs of health care due to the physical and psycho-social problems caused by obesity and related complications, coupled with the associated loss of productivity, is staggering. Improving strategies to induce lifestyle changes among the obese and overweight population is a necessary strategy toward alleviating this problem, but this approach should be complemented by continued basic research addressing the physiological processes regulating weight gain and adipose formation. While the reguIaton of adipogenesis by adipogenic transcription factors has been extensive(y examined, epigenetic regulators of adipogenesis have not received as much attention. We provide evidence that ATP-dependent chromatin remodeling enzymes and arginine methyltransferases are critical regulators of adipose formation and propose to investigate the mechanisms of action of these enzymes in adipose formation and function in culture and in vivo. Specifically, we will investigate the functional contributions of the histone arginine methyltransferases Prmt5 and Prmt4 in regulating adipogenic gene expression. Additional effort will be placed on investigating the dynamics of histone arginine methylation during adipose formation and function by examining arginine demethylase enzymes. Modulation of epigenetic regulators of gene expression has already proven clinically useful: understanding how such regulators function potentially may lead to strategies that modulate adipogenesis in a manner that is useful for the treatment of obesity and obesity related disease.

肥胖和与肥胖相关的健康并发症，包括糖尿病，影响了美国相当大比例的人口，预测表明，肥胖和超重的人数未来将继续上升。由于肥胖和相关并发症造成的身体和心理社会问题，加上相关的生产力损失，医疗保健费用令人震惊。 改善在肥胖和超重人群中诱导生活方式改变的策略是缓解这一问题的必要策略，但这种方法应该得到持续的基础研究的补充，这些研究涉及调节体重增加和脂肪形成的生理过程。虽然成脂转录因子对成脂的调节作用已被广泛研究，但表观遗传调控的成脂作用还没有受到广泛的关注。我们提供的证据表明，依赖于ATP的染色质重塑酶和精氨酸甲基转移酶是脂肪形成的关键调节因子，并建议在培养和体内研究这些酶在脂肪形成和功能中的作用机制。具体地说，我们将研究组蛋白精氨酸甲基转移酶PRMT5和PrMT4在调节成脂基因表达中的功能贡献。此外，还将通过检测精氨酸脱甲基酶来研究组蛋白精氨酸甲基化在脂肪形成和功能过程中的动态。表观遗传调节基因表达的调节已经被证明在临床上是有用的：了解这些调节因子如何潜在地发挥作用可能导致以一种对肥胖和肥胖相关疾病的治疗有用的方式来调节脂肪生成的策略。