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Oxytocin and Weight Loss in Humans

催产素与人类减肥

基本信息

批准号：
9921423
负责人：
Elizabeth Austen Lawson
金额：
$ 69.32万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-05-01 至 2023-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9921423
关键词：
Address Affect Age Animal Model Anterior Basal Ganglia Body Composition Body Weight decreased Body fat Brain region Data Desire for food Diet Dose Double-Blind Method Eating Energy Intake Energy Metabolism Fasting Fatty acid glycerol esters Food Food Energy Functional Magnetic Resonance Imaging Gender Human Hypothalamic Hormones Impulsive Behavior Impulsivity Investigation Knowledge Leptin Lipolysis Liver Mediating Modeling Monkeys Motivation Neural Pathways Neurons Neurosecretory Systems Obese Mice Obesity Overweight Oxytocin Oxytocin Receptor Pathway interactions Patients Peptides Peripheral Pharmaceutical Preparations Physiological Placebos Prefrontal Cortex Premature Mortality Public Health Randomized Rattus Rest Rewards Rodent Safety Serum Stimulus Testing Translating Translations Triglycerides Ventral Tegmental Area Visceral Visceral fat Visit Visual Weight Weight Gain Weight-Loss Drugs Woman adult obesity alpha-Melanocyte stimulating hormone behavior measurement cingulate cortex clinically relevant comorbidity feeding follow-up food consumption men mind control neuroimaging neuroregulation nonhuman primate novel therapeutics obesity management oxidation placebo controlled study pre-clinical preclinical study prevent primary endpoint randomized placebo controlled study reduced food intake relating to nervous system respiratory response side effect treatment optimization

项目摘要

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.

项目摘要/摘要