Regulatory Responses to Positive Energy Balance

对正能量平衡的监管反应

基本信息

批准号：
7008504
负责人：
RANDY J SEELEY
金额：
$ 25.62万
依托单位：
UNIVERSITY OF CINCINNATI
依托单位国家：
美国
项目类别：
财政年份：
1997
资助国家：
美国
起止时间：
1997-09-30 至 2007-01-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): The incidence of obesity has reached epidemic proportions, is a major health burden, and costs the U.S. billions of dollars in health care and lost productivity. Failure to develop effective treatments for obesity is in large part due to a lack of clear understanding as to how food intake and energy balance are regulated by the CNS. Thus, research to determine the processes by which food intake and energy balance are controlled is likely to have a major impact on public health, but the research to date has been imbalanced. For whereas considerable effort has been devoted to understanding the neurochemical response to negative energy balance, relatively little attention has been devoted to the inverse situation of positive energy balance. This oversight is significant since obesity is necessarily associated with periods of positive energy balance and therefore can be considered as a failure of the body weight regulatory system to respond appropriately to positive energy balance. Thus studying the responses to positive energy balance may provide valuable clues concerning the etiology of obesity. Moreover, the regulatory responses to positive energy balance represent the recruitment of endogenous systems that produce reduced food intake, increased energy expenditure and significant weight loss. Finding potential ways to mimic or trigger these endogenous regulatory response systems could provide unique insights and therapeutic strategies for the treatment of obesity. The current proposal seeks to identify critical aspects of this response system. When animals are force-fed calories in excess of caloric need (involuntary overfeeding), their spontaneous food intake drops to near zero and they gain body weight. Additionally, for some time after the overfeeding regimen is terminated, spontaneous food intake remains low until body weight has returned to control levels. Our data indicate that this regulatory response to positive energy balance is mediated by the CNS melanocortin system. We propose assessing several hypotheses concerning how the CNS melanocortin system orchestrates the response to positive energy balance. First, we will determine the critical population of melanocortin receptors that mediate the reduced food intake and increased energy expenditure that follow a period of positive energy balance. Second, we will determine the critical inputs into the melanocortin system that signal positive energy balance. Finally, we will evaluate the unique effects of an endogenous melanocortin receptor antagonist that counteracts the normal response to positive energy balance. The information from this proposal will be critical to a complete picture of how energy balance is regulated and how disorders of energy balance such as obesity may be treated.

描述（由申请人提供）：肥胖的发生率已达到流行比例是一个重大的健康负担，损失了美国数十亿美元卫生保健的美元和生产力损失。未能发展有效肥胖治疗很大程度上是由于缺乏明确的理解对于如何通过中枢神经系统调节食物的摄入和能量平衡。因此，研究确定食物摄入和能量平衡的过程受控可能会对公共卫生产生重大影响，但研究迄今为止一直不平衡。尽管大量努力要了解对负能量平衡的神经化学反应，相对较少关注的关注是对正能量平衡。这种监督很重要，因为肥胖是一定与正能量平衡时期有关，因此可以认为是体重调节系统的失败适当地达到正能量平衡。因此研究了对正能量平衡可能会提供有关病因的宝贵线索肥胖。此外，对正能量平衡的监管响应代表招募内源系统，产生减少的食物摄入量，能量消耗增加和重大减肥。发现模仿或触发这些内源性调节响应系统的潜在方法可以提供独特的见解和治疗策略来治疗肥胖。当前的提案旨在确定这一点的关键方面响应系统。当动物是力量的卡路里，超出了热量需求时（非自愿过度喂养），他们自发的食物摄入量降至零接近，并获得体重。此外，在过度喂养方案之后的一段时间内终止，自发的食物摄入量保持较低，直到体重恢复控制水平。我们的数据表明，这种对正面的调节反应能量平衡是由CNS黑色素皮质系统介导的。我们提出评估关于CNS黑素皮质素系统如何协调的几个假设对正能量平衡的响应。首先，我们将确定关键介导降低的食物摄入量和遵循正能量平衡时期的能量消耗增加。其次，我们将确定对黑色皮质素系统的关键输入信号正能量平衡。最后，我们将评估内源性黑色皮质素受体拮抗剂，以应对正常对正能量平衡的响应。该提议的信息将是对能源平衡的调节方式以及如何进行的完整情况至关重要可以治疗肥胖等能量平衡的疾病。

项目成果

期刊论文数量（31）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Central amylin signaling and the regulation of energy homeostasis.

中央胰淀素信号传导和能量稳态的调节。

DOI：
10.2174/1381612033455387
发表时间：
2003
期刊：
Current pharmaceutical design
影响因子：
3.1
作者：
Rushing,PaulA
通讯作者：
Rushing,PaulA

Neuropeptide Y prepares rats for scheduled feeding.

神经肽 Y 使大鼠做好按计划喂养的准备。

DOI：
10.1152/ajpregu.00817.2004
发表时间：
2005
期刊：
American journal of physiology. Regulatory, integrative and comparative physiology
影响因子：
0
作者：
Drazen,DeborahL;Wortman,MatthewD;Seeley,RandyJ;Woods,StephenC
通讯作者：
Woods,StephenC

The effect of adrenalectomy on ghrelin secretion and orexigenic action.

肾上腺切除术对生长素释放肽分泌和食欲作用的影响。

DOI：
10.1111/j.1365-2826.2005.01322.x
发表时间：
2005
期刊：
Journal of neuroendocrinology.
影响因子：
0
作者：
Proulx,K;Vahl,TP;Drazen,DL;Woods,SC;Seeley,RJ
通讯作者：
Seeley,RJ

The role of the transcription factor ETV5 in insulin exocytosis.

DOI：
10.1007/s00125-013-3096-5
发表时间：
2014-02
期刊：
DIABETOLOGIA
影响因子：
8.2
作者：
Gutierrez-Aguilar, Ruth;Kim, Dong-Hoon;Casimir, Marina;Dai, Xiao-Qing;Pfluger, Paul T.;Park, Jongsun;Haller, April;Donelan, Elizabeth;Park, Jisoo;D'Alessio, David;Woods, Stephen C.;MacDonald, Patrick E.;Seeley, Randy J.
通讯作者：
Seeley, Randy J.

Sexually dimorphic responses to fat loss after caloric restriction or surgical lipectomy.