Epigenetic Control of Adipogenesis

肥胖症和与肥胖症相关的健康并发症，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个体的数量在未来将继续上升。由于肥胖症和相关并发症造成的身体和心理社会问题，再加上相关的生产力损失，保健费用惊人。 改善肥胖和超重人群的生活方式改变的策略是缓解这一问题的必要策略，但这种方法应该通过持续的基础研究来补充，以解决调节体重增加和脂肪形成的生理过程。虽然脂肪形成转录因子对脂肪形成的调节作用已被广泛研究，但脂肪形成的表观遗传调节因子还没有得到足够的关注。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，并建议调查这些酶在脂肪形成和功能的作用机制，在文化和体内。具体而言，我们将研究组蛋白精氨酸甲基转移酶Prmt 5和Prmt 4在调节成脂基因表达中的功能贡献。另外的努力将放在调查组蛋白精氨酸甲基化的动态过程中脂肪的形成和功能，通过检查精氨酸脱甲基酶。基因表达的表观遗传调节因子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会导致以可用于治疗肥胖症和肥胖症相关疾病的方式调节脂肪形成的策略。

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.