Oxytocin and Weight Loss in Humans
Oxytocin and Weight Loss in Humans
批准号:
9921423
负责人:
Elizabeth Austen Lawson
金额:
$69.32万
依托单位国家:
美国
项目类别:
财政年份:
2017
资助国家:
美国
项目状态:
已结题
起止时间:
2017-05-01 至 2023-04-30
关键词:
AddressAffectAgeAnimal ModelAnteriorBasal GangliaBody CompositionBody Weight decreasedBody fatBrain regionDataDesire for foodDietDoseDouble-Blind MethodEatingEnergy IntakeEnergy MetabolismFastingFatty acid glycerol estersFoodFood EnergyFunctional Magnetic Resonance ImagingGenderHumanHypothalamic HormonesImpulsive BehaviorImpulsivityInvestigationKnowledgeLeptinLipolysisLiverMediatingModelingMonkeysMotivationNeural PathwaysNeuronsNeurosecretory SystemsObese MiceObesityOverweightOxytocinOxytocin ReceptorPathway interactionsPatientsPeptidesPeripheralPharmaceutical PreparationsPhysiologicalPlacebosPrefrontal CortexPremature MortalityPublic HealthRandomizedRattusRestRewardsRodentSafetySerumStimulusTestingTranslatingTranslationsTriglyceridesVentral Tegmental AreaVisceralVisceral fatVisitVisualWeightWeight GainWeight-Loss DrugsWomanadult obesityalpha-Melanocyte stimulating hormonebehavior measurementcingulate cortexclinically relevantcomorbidityfeedingfollow-upfood consumptionmenmind controlneuroimagingneuroregulationnonhuman primatenovel therapeuticsobesity managementoxidationplacebo controlled studypre-clinicalpreclinical studypreventprimary endpointrandomized placebo controlled studyreduced food intakerelating to nervous systemrespiratoryresponseside effecttreatment optimization
中文摘要
项目总结/摘要
肥胖症患者的有意义的体重减轻难以实现和维持,可用的治疗方法
重大限制。催产素(OXT),一种调节食物摄入和能量的下丘脑激素
代谢,是一个令人兴奋的潜在的新的治疗肥胖管理。一项针对肥胖成年人的小型研究
经8周鼻内(IN)OXT治疗,在拟定剂量下体重减轻近20磅。数据
啮齿动物和非人类灵长类动物模型表明,OXT通过(1)增加能量
消耗,(2)诱导脂肪分解,和(3)减少食物消耗。我们提出一个随机的安慰剂-
持续IN OXT的对照研究,以确定OXT是否减轻体重、增加能量
在动物模型中,它可以减少肥胖人群的总脂肪、内脏脂肪和肝脏脂肪。我们还将
使用最先进的技术来表征持续OXT对热量摄入和相关神经通路的影响。
神经内分泌、神经影像和行为测量。在一项针对60名肥胖男女的研究中,
假设与安慰剂相比,8周IN OXT(24 IU qid)将导致(a)体重减轻,(B)
增加静息能量消耗;和(c)减少全身、内脏和肝脏脂肪。根据我们之前
研究结果表明,OXT可能通过调节奖励和冲动控制来减轻体重
神经通路抑制进食,我们进一步假设OXT将导致在测试中减少热量摄入
与安慰剂相比,与体重变化无关,通过(a)减少空腹和餐后
进食时fMRI激活奖励相关食物动机脑区(腹侧被盖区,基底神经节)
使用视觉食物刺激范例;和(B)增加的冲动控制伴随增加的fMRI
冲动控制脑区(前扣带回、背外侧前额叶)的激活和功能连接
皮层)在需要参与脉冲控制以抑制脉冲反应的有效任务期间。
这项研究将证明其有效性,并增加我们对IN潜在机制的理解
OXT作为一种潜在的减肥药物-临床前研究结果转化为人类的关键步骤,
优化肥胖患者的治疗方案。
英文摘要
Project Summary / Abstract
Meaningful weight reduction in obesity is difficult to achieve and sustain, and available therapies have
significant limitations. Oxytocin (OXT), a hypothalamic hormone that regulates food intake and energy
metabolism, is an exciting potential novel therapeutic in obesity management. A small study of obese adults
demonstrated weight loss of nearly 20 lbs with 8 weeks of intranasal (IN) OXT at the proposed dose. Data in
rodent and nonhuman primate models indicate that OXT drives weight loss by (1) increasing energy
expenditure, (2) inducing lipolysis, and (3) reducing food consumption. We propose a randomized, placebo-
controlled study of sustained IN OXT to determine whether OXT reduces body weight, increases energy
expenditure and reduces total, visceral and liver fat in obese humans, as it does in animal models. We will also
characterize the effects of sustained OXT on caloric intake and relevant neural pathways using cutting-edge
neuroendocrine, neuroimaging, and behavioral measures. In a study of 60 obese men and women, we
hypothesize that eight weeks of IN OXT (24 IU qid) compared to placebo will result in (a) weight loss, (b)
increased resting energy expenditure; and (c) reduced total body, visceral and liver fat. Building on our prior
findings indicating that OXT may achieve weight reduction in part by modulating reward and impulse control
neural pathways to curb eating, we further hypothesize that OXT will result in reduced caloric intake at a test
meal, independent of change in weight, compared to placebo, mediated by (a) reduced fasting and post-
prandial fMRI activation of reward-related food motivation brain regions (ventral tegmental area, basal ganglia)
using a visual food stimuli paradigm; and (b) increased impulse control accompanied by increased fMRI
activation and functional connectivity of impulse control brain regions (anterior cingulate, dorsolateral prefrontal
cortex) during a validated task requiring the engagement of impulse control to suppress impulsive responses.
This study will demonstrate the efficacy and increase our understanding of the underlying mechanisms of IN
OXT as a potential weight loss drug -- critical steps in the translation of preclinical findings to humans and
optimizing therapies for patients with obesity.
期刊论文(2)
专著(0)
科研奖励(0)
会议论文
DOI:
10.1016/b978-0-12-820107-7.00006-9
发表时间:
2021
期刊:
Handbook of clinical neurology
影响因子:
--
作者:
[Liya Kerem;E. Lawson]
通讯作者:
Liya Kerem;E. Lawson
DOI:
10.3390/ijms22147737
发表时间:
2021-07-20
期刊:
International journal of molecular sciences
影响因子:
5.6
作者:
[Kerem L, Lawson EA]
通讯作者:
Lawson EA
Neurobiology of avoidant/restrictive eating in youth
-
批准号:10210232
-
项目类别:
-
资助金额:$19.22万
-
财政年份:2019
-
负责人:Elizabeth Austen Lawson
-
依托单位:
Neurobiology of avoidant/restrictive eating in youth
-
批准号:10460510
-
项目类别:
-
资助金额:$19.22万
-
财政年份:2019
-
负责人:Elizabeth Austen Lawson
-
依托单位:
Neurobiology of avoidant/restrictive eating in youth
-
批准号:10676326
-
项目类别:
-
资助金额:$19.22万
-
财政年份:2019
-
负责人:Elizabeth Austen Lawson
-
依托单位:
Neurobiology of avoidant/restrictive eating in youth
-
批准号:9982437
-
项目类别:
-
资助金额:$19.22万
-
财政年份:2019
-
负责人:Elizabeth Austen Lawson
-
依托单位:
Neurobiology of avoidant/restrictive eating in youth
-
批准号:9804413
-
项目类别:
-
资助金额:$19.22万
-
财政年份:2019
-
负责人:Elizabeth Austen Lawson
-
依托单位:
Oxytocin and Weight Loss in Humans
-
批准号:9309526
-
项目类别:
-
资助金额:$63.68万
-
财政年份:2017
-
负责人:Elizabeth Austen Lawson
-
依托单位:
Neurobiological and Behavioral Risk Mechanisms of Youth Avoidant/Restrictive Eating Trajectories
-
批准号:10120795
-
项目类别:
-
资助金额:$8.4万
-
财政年份:2016
-
负责人:Elizabeth Austen Lawson
-
依托单位:
Neurobiological and Behavioral Risk Mechanisms of Youth Avoidant/Restrictive Eating Trajectories
-
批准号:9244073
-
项目类别:
-
资助金额:$71.37万
-
财政年份:2016
-
负责人:Elizabeth Austen Lawson
-
依托单位:
Neurobiological and Behavioral Risk Mechanisms of Youth Avoidant/Restrictive Eating Trajectories
-
批准号:9433685
-
项目类别:
-
资助金额:$56.5万
-
财政年份:2016
-
负责人:Elizabeth Austen Lawson
-
依托单位:
Appetite-regulating Hormones and Neurocircuitry in Anorexia Nervosa
-
批准号:8676505
-
项目类别:
-
资助金额:$18.69万
-
财政年份:2011
-
负责人:Elizabeth Austen Lawson
-
依托单位:
Appetite-regulating Hormones and Neurocircuitry in Anorexia Nervosa
-
批准号:8298137
-
项目类别:
-
资助金额:$18.69万
-
财政年份:2011
-
负责人:Elizabeth Austen Lawson
-
依托单位:
Appetite-regulating Hormones and Neurocircuitry in Anorexia Nervosa
-
批准号:8190652
-
项目类别:
-
资助金额:$18.69万
-
财政年份:2011
-
负责人:Elizabeth Austen Lawson
-
依托单位:
Appetite-regulating Hormones and Neurocircuitry in Anorexia Nervosa
-
批准号:8485681
-
项目类别:
-
资助金额:$18.69万
-
财政年份:2011
-
负责人:Elizabeth Austen Lawson
-
依托单位:
海外基金