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Oxytocin as a Neuroendocrine Therapy for Obesity in Youth

催产素作为青少年肥胖症的神经内分泌疗法

基本信息

批准号：
10435539
负责人：
Miriam Antoinette Bredella
金额：
$ 72.13万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-17 至 2026-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10435539
关键词：
18 year old Adolescence Adolescent Adolescent obesity Adult Animal Model Anti-Inflammatory Agents Automobile Driving Behavior Body Composition Body Weight Body Weight decreased Body mass index Child Data Diet Dose Dual-Energy X-Ray Absorptiometry Dyslipidemias Early treatment Eating Eating Behavior Elderly Energy Intake Energy Metabolism Epidemic Executive Dysfunction Fasting Fatty acid glycerol esters Food Energy Heart Diseases Hepatic Hunger Hypothalamic Hormones Hypothalamic structure Image Indirect Calorimetry Individual Inflammation Interleukin-6 Intervention Investigation Life Lipids Lipoproteins Magnetic Resonance Imaging Measures Mediating Medical Metabolic Monkeys Motor Activity Neuroendocrine Therapy Neurosecretory Systems Obesity Overweight Oxytocin Pharmaceutical Preparations Physical activity Physiological Physiology Placebo Control Placebos Population Property Quality of life Randomized Randomized, Controlled Trials Rattus Rest Risk Risk Marker Rodent Rodent Model Safety Serum Single-Blind Study TNF gene Taste Perception Testing Therapeutic Therapeutic Agents Thermogenesis Thinness Time Triglycerides Visceral Weight Weight Gain Youth adult obesity cardiometabolic risk comorbidity critical period developmental plasticity diet-induced obesity efficacy study energy balance food consumption improved intrahepatic lifestyle intervention mortality muscle form neuroinflammation nonhuman primate novel novel therapeutics obese patients obesity treatment peptide hormone preservation prevent randomized placebo controlled study reduced food intake systemic inflammatory response therapeutically effective young adult

项目摘要

PROJECT ABSTRACT Obesity in adolescence and young adulthood is epidemic, leading to increased metabolic risk later in life. The extent of weight loss through lifestyle interventions is variable and difficult to sustain. Existing medical therapies for adults, which are often not FDA-approved in children, may lead to modest weight loss, but effects are difficult to sustain, and these medications are limited by their tolerability. Oxytocin (OXT), a hypothalamic hormone that regulates food intake and energy metabolism, is an exciting potential novel therapeutic in this population. Intranasal (IN) OXT induced marked weight loss and was well tolerated in a small 8-week study of adults with obesity. Our preliminary data show reduction in BMI SDS with excellent tolerability with 6-months of IN OXT in 5-18-year-old children across a range of BMIs. Data in rodent and nonhuman primates indicate that OXT drives weight loss by reducing food consumption and increasing energy expenditure. Importantly, OXT also has the potential to reduce metabolic risk through reduction in visceral and hepatic fat, reduced inflammation, and improved lipids. In fact, OXT has recently been shown to reduce neuroinflammation, and hypothalamic inflammation in rodent models with obesity. We propose a randomized, placebo-controlled study of twelve weeks of IN OXT vs. placebo to determine whether OXT reduces weight and metabolic risk markers in adolescents with obesity as it does in diet-induced obese animal models. We will also investigate underlying mechanisms driving OXT effects using cutting-edge imaging and metabolic assessments. In a study of 75 adolescents with obesity, we hypothesize that twelve weeks of IN OXT compared to placebo will result in (1) reduced BMI SDS from (a) decreased food intake in the fasting state and in the absence of hunger, and (b) increased resting energy expenditure and diet-induced thermogenesis, mediated by reduced measures of hypothalamic inflammation; and (2) reduced visceral and intrahepatic fat with relative preservation of lean/muscle mass, associated with reduced systemic inflammation and an improved lipid profile. This study will be the first to systematically investigate the efficacy and safety of OXT as a novel therapeutic agent to induce weight loss and improve indicators of metabolic risk in adolescents with obesity.

项目摘要