Transcriptional control in brown and beige adipocytes

棕色和米色脂肪细胞的转录控制

• 批准号: 8984492
• 负责人: Biao Wang
• 金额: $ 35.66万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-01 至 2020-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8984492
• 关键词: Acute; Adenylate Cyclase; Adipocytes; Adipose tissue; Adrenergic Receptor; Adult; Affect; Applications Grants; Biological; Body mass index; Brown Fat; CREB1 gene; Catecholamines; Cell model; Chronic; Complex; Cyclic AMP; Cyclic AMP-Dependent Protein Kinases; Development; Diet; Energy Intake; Energy Metabolism; Environment; Event; Exhibits; Fatty acid glycerol esters; Food; HDAC4 gene; Heating; Histones; Homeostasis; Hormones; Human; Insulin Resistance; Investigation; Knockout Mice; Life; Mediating; Metabolic; Metabolic Diseases; Mitochondria; Molecular; Molecular Target; Mus; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Organism; Performance; Phosphorylation; Physiologic Thermoregulation; Physiological; Process; Protein Dephosphorylation; Proteins; Respiration; Role; Signal Transduction; Single Nucleotide Polymorphism; Site; Stimulus; Sympathetic Nervous System; Temperature; Thermogenesis; Tissues; Transcription Coactivator; Transcriptional Regulation; adipocyte differentiation; cell type; energy balance; environmental change; gain of function; improved; insulin sensitivity; mouse model; new therapeutic target; programs; public health relevance; response; salt-inducible kinase; uncoupling protein 1

 DESCRIPTION (provided by applicant: Energy balance is the biological homeostasis of energy in living organisms, which means energy intake from food equals energy expenditure. When energy intake exceeds energy expenditure, excess energy will be stored as fat in adipose and other metabolic tissues, eventually leading to obesity and further development into type II diabetes. Adaptive thermogenesis represents one principle component of total energy expenditure, which refers to body heat production in response to changes of environmental temperature or diet. Brown adipose tissue is the major site of adaptive thermogenesis to dissipate energy. Recent studies indicate that brown and brown like fat (beige fat) are present in adult human, and their activities are inversely correlated with body mass index. Both cold exposure and circulating hormones can activate sympathetic nervous system to have acute and chronic impacts on brown and beige fat, although the molecular mechanisms still remain poorly understood. This Grant proposal aims to elucidate the function of a molecular switch in brown and beige fat to govern energy expenditure. In this proposal, the physiological role of this switch will be investigated using cellular and mouse models. The way that cold exposure and hormones turn on this switch and the molecular events afterwards in brown and beige fat will be studied. How dysregulation of this switch contributes to metabolic disorders will also be explored. Therefore, targeting this molecular switch in human may provide new therapies to treat obesity and type II diabetes.

 描述(申请人提供：能量平衡是生物体中能量的生物平衡，即从食物中摄取的能量等于能量消耗。当能量摄入超过能量消耗时，多余的能量将以脂肪的形式储存在脂肪和其他代谢组织中，最终导致肥胖并进一步发展为II型糖尿病。适应性生热是总能量消耗的一个主要组成部分，指的是人体对环境温度或饮食的变化所产生的热量。棕色脂肪组织是适应性产热散热的主要场所。最近的研究表明，棕色和棕色样脂肪(米色脂肪)存在于成年人中，它们的活动与体重指数呈负相关。冷暴露和循环激素都可以激活交感神经系统，对棕色和米色脂肪产生急性和慢性影响，尽管分子机制仍然知之甚少。这项格兰特提案旨在阐明棕色和米色脂肪中分子开关控制能量消耗的功能。在这个提议中，这个开关的生理作用 将使用细胞和小鼠模型进行研究。冷暴露和荷尔蒙开启这一开关的方式以及随后棕色和米色脂肪中的分子事件将被研究。此外，还将探讨这种转换的失调如何导致代谢紊乱。因此，针对人类的这种分子开关可能会提供治疗肥胖症和II型糖尿病的新疗法。