Photoperiodic Control of Obesity

光周期控制肥胖

基本信息

批准号：
8836671
负责人：
Timothy Jon Bartness
金额：
$ 49.59万
依托单位：
GEORGIA STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-09-18 至 2019-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8836671
关键词：
Address Adipocytes Adipose tissue Adult Autologous Basic Science Behavioral Biological Assay Brain Brown Fat Deposition Dopamine-beta-monooxygenase Economic Burden FOS gene Fatty acid glycerol esters Food deprivation (experimental)Glucose Glycerol Hepatic Hormones Human In Vitro Injection of therapeutic agent Instruction Label Left Leptin Link Lipids Lipolysis Liver Measurement Measures Medical Economics Melanocortin 4 Receptor Mesentery Messenger RNA Metabolic Metabolic syndrome Methods Muscle Neurons Neurotransmitters Nonesterified Fatty Acids Norepinephrine Obesity Oranges Partner in relationship Pattern Phosphorylation Physiological Progress Reports Proteins Publishing Relative (related person)Retroperitoneal Space Rodent Role Sensory Single Nucleotide Polymorphism Site Stimulus Suid Herpesvirus 1 Sympathetic Nervous System Temperature Testing Therapeutic Thermogenesis Tissues Tracer Transplantation Triglycerides Viral Visceral Western Blotting Work afferent nerve clinical application clinically significant cytokine feeding glucose analog hindbrain in vivo innovation insight intraperitoneal melanocortin receptor melanotan-II nerve supply paracrine perilipin A reinnervation release factor response sensory system sterol esterase subcutaneous vpr Genes

项目摘要

More than one-third of adults were obese in 2012 with the percentage of adults that are ovenweight or obese at -67% in the USA. and the annual medical economic burden of obesity was ~$147 billion in 2008 dollars in the USA. Thus, there is a need for further basic research with clinical significance to obesity reversal therapies. The proposed work will continue the exploration ofthe roles ofthe sympathetic nervous system (SNS) and sensory system (SS) in white adipose tissue (WAT) and brown adipose tissue (BAT) function in obesity reversal. The role ofthe WAT SS is virtually unknown; therefore, we will: a) determine the physiological and behavioral responses triggered by the WAT-produced cytokine leptin, but leptin acting as a paracrine factor to increase sensory afferent activity and b) identify the lipolysis-associated stimuli that increases sensory nerve activity using electrophysiological and functional histological (c-Fos) measures for both. BAT sensory nerves will be tested for responsiveness to changes in its temperature. WAT and BAT transplants appear to correct metabolic dysregulafions suggesting potential clinical application, yet the hypothesized underlying mechanisms involve transplant-released factors without consideration of graft reinnervation now known to exist. Thus, comparisons ofthe SNS/SS innervation patterns of WAT and BAT autologous transplants using viral transneuronal tract tracing and their functional responses with their endogenous mates will be made. Glucoprivation triggers large WAT SNS drive increases, a glucocompensatory response. Other glucocompensatory responses are located in the hindbrain. The CNS sites sensitive to decreases in glucose utilization will be tested using hindbrain parenchymal injections of an anti-glucose analogue to trigger SNS drive increases and attempts to block glucoprivation-induced increases in SNS drive will be made by immunolesioning likely hindbrain sites-of-action with saporin conjugated anti- dopamine-beta hydroxylase.. Adipocyte proliferation is the hallmark of obesity, yet it is rarely studied. The mechanisms underlying the in vivo, and in vitro inhibition of white adipocyte proliferation by the SNS and its neurotransmitter norepinephrine will be determined using a primary adipocyte culture assay. RELEVANCE (See instructions): These conceptually and technically innovative topics/approaches will propel the field forward toward a deeper understanding for the role of WAT/BAT SNS/SS innervations that should have high clinical significance for therapeutic strategies to trigger obesity reversal

2012 年，超过三分之一的成年人肥胖，体重或肥胖的成年人百分比美国为-67%。以 2008 年美元计算，肥胖每年造成的医疗经济负担约为 1,470 亿美元在美国。因此，需要进一步开展对肥胖逆转具有临床意义的基础研究疗法。拟议的工作将继续探索交感神经系统的作用白色脂肪组织（WAT）和棕色脂肪组织（BAT）中的（SNS）和感觉系统（SS）在肥胖逆转。 WAT SS 的作用几乎无人知晓；因此，我们将： a) 确定 WAT 产生的细胞因子瘦素触发的生理和行为反应，但瘦素充当旁分泌因子以增加感觉传入活动，b) 识别与脂肪分解相关的刺激使用电生理学和功能组织学 (c-Fos) 测量来增加感觉神经活动两个都。 BAT 感觉神经将接受对其温度变化的反应能力测试。 WAT 和 BAT 移植似乎可以纠正代谢失调，这表明潜在的临床应用，但假设的潜在机制涉及移植释放因子，而不考虑移植物现在已知存在神经再生。因此，WAT 和 BAT 的 SNS/SS 神经支配模式的比较使用病毒跨神经元束示踪的自体移植及其功能反应将会产生内源性伴侣。 Glucoprivation 引发大量 WAT SNS 驱动力增加，葡萄糖代偿反应。其他葡萄糖补偿反应位于后脑。中枢神经系统对葡萄糖利用率降低敏感的位点将使用后脑实质注射进行测试抗葡萄糖类似物触发 SNS 驱动力增加并试图阻止葡萄糖缺乏引起的增加在SNS驱动中，将通过用皂素结合的抗-免疫损伤可能的后脑作用位点来实现多巴胺-β羟化酶。脂肪细胞增殖是肥胖的标志，但很少有人对此进行研究。这 SNS 及其在体内和体外抑制白色脂肪细胞增殖的机制神经递质去甲肾上腺素将使用原代脂肪细胞培养测定来测定。相关性（参见说明）：这些概念和技术上的创新主题/方法将推动该领域朝着对 WAT/BAT SNS/SS 神经支配的作用有更深入的了解，这应该具有较高的临床意义触发肥胖逆转的治疗策略的意义