Epigenetic Control of Adipogenesis

脂肪生成的表观遗传控制

基本信息

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
项目类别：
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

项目摘要

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）影响着美国很大一部分人口，预测表明未来肥胖和超重人数将继续增加。肥胖和相关并发症引起的身体和心理社会问题以及相关的生产力损失导致的医疗费用令人震惊。改善肥胖和超重人群生活方式改变的策略是缓解这一问题的必要策略，但这种方法应该辅之以持续的基础研究，解决调节体重增加和脂肪形成的生理过程。虽然脂肪生成转录因子对脂肪生成的调节已被广泛研究，但脂肪生成的表观遗传调节剂尚未受到足够的关注。我们提供的证据表明 ATP 依赖性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剂，并建议研究这些酶在培养物和体内脂肪形成和功能中的作用机制具体来说，我们将研究组蛋白精氨酸的功能贡献。甲基转移酶 Prmt5 和 Prmt4 在调节脂肪形成基因表达中的作用将通过检查精氨酸去甲基化酶来研究脂肪形成和功能过程中组蛋白精氨酸甲基化的动态，该酶已被证明具有临床用途：了解其如何发挥作用。调节剂的功能可能会导致以可用于治疗肥胖和肥胖相关疾病的方式调节脂肪生成的策略。