Effect of Pre and Postnatal Nutritional Programming on SCD1 Activity and Obesity

产前和产后营养规划对 SCD1 活性和肥胖的影响

• 批准号: 7910710
• 负责人: JENNIFER K YEE
• 金额: $ 15.72万
• 依托单位: LUNDQUIST INSTITUTE FOR BIOMEDICAL INNOVATION AT HARBOR-UCLA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-01 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7910710
• 关键词: Adipocytes; Affect; Animals; Appetite Regulation; Biochemical Markers; Biochemical Pathway; Biological Markers; Body Composition; Cell Culture Techniques; Characteristics; Child; Childhood; Clinical; Clinical Research; Clinical Research Curriculum Award; Desire for food; Development; Diabetes Mellitus; Eating; Education; Endocrinologist; Environment; Enzymes; Fatty Acids; Feedback; Gene Proteins; Goals; Heart Diseases; Human; Hyperphagia; Hypothalamic structure; Infant; Insulin Resistance; Laboratories; Lead; Life; Malnutrition; Measures; Mentors; Metabolic; Metabolic syndrome; Metabolism; Methods; Modeling; Monounsaturated Fatty Acids; Newborn Infant; Nutrient; Nutritional; Obesity; Overnutrition; Pathway interactions; Phenotype; Physiological; Plasma; Prenatal Nutrition; Prevalence; Prevention strategy; Rattus; Regulation; Research; Research Activity; Research Personnel; Research Project Grants; Research Training; Risk; Role; Saturated Fatty Acids; Signal Transduction; Stearoyl-CoA Desaturase; System; Time; Tissues; Translational Research; Up-Regulation; adipocyte differentiation; career; cohort; directed attention; fatty acid metabolism; fetal; gene induction; human subject; in utero; in vivo; indexing; lipid biosynthesis; nutrition; obesity in children; obesity prevention; obesity risk; offspring; postnatal; prenatal; programs; protein expression; research study; responsible research conduct; skills; stable isotope; tissue/cell culture; translational study

DESCRIPTION (provided by applicant): Project Summary: Jennifer K. Yee is a pediatric endocrinologist at Harbor-UCLA establishing her academic career studying the role of stearoyl-CoA desaturase enzyme-1 (SCD1) and fatty acid synthesis pathways in nutritional programming for obesity. As a fellow, Dr. Yee explored SCD1 inhibition using stable isotope methods under the guidance of Dr. W.N. Paul Lee. Motivated by the increasing prevalence of childhood obesity, she has directed her attention to the role of SCD1 in nutritional programming. Dr. Yee's long-term goal is to become an independent investigator and identify treatment and prevention strategies for obesity through studies on fatty acid metabolism in adipogenesis and adipocyte differentiation. Dr. Yee's immediate goal is to establish her research focus while acquiring the skills necessary for independence. Dr. Yee's proposed research activities will be supplemented by didactic education including the UCLA K30 program and the Responsible Conduct of Research course. Dr. Yee will be mentored by Dr. W.N. Paul Lee, an expert in intermediary metabolism, and Co-Sponsor Dr. Michael Ross, an expert in appetite regulation in nutritional programming. Collaborator Mina Desai will also support Dr. Yee's research training. Harbor-UCLA is an excellent academic environment for Dr. Yee, who will receive departmental and divisional support for 75% protected time, and GCRC support for her project. Clinical, laboratory, and technical environments are outstanding. The research project combines clinical and translational research studies that aim to establish the role of SCD1 in prenatal and postnatal nutritional programming. The clinical study follows newborns at risk for obesity from in utero nutritional programming over three years. Plasma fatty acid ratios representing SCD1 activity, called the desaturation indices, will be measured yearly along with body composition and biochemical markers. The parallel translational study will measure desaturation indices, and SCD1 gene and protein expression in a rat model of nutritional programming for obesity. Effects of SCD1 inhibition will be studied ex vivo in primary tissue cell culture and in vivo in the rat model. The purpose is to establish the principle that SCD1 upregulation occurs as a result of in utero programming and that inhibition of SCD1 activity can modulate development of obesity. Relevance: Too much or too little nutrition during pregnancy, called nutritional programming, can lead to offspring obesity and related problems. Changes in the fatty acid synthesis pathways from increased activity in the enzyme SCD1 have been implicated in the development of obesity, diabetes, and heart disease. The objective of this project is to establish the role of SCD1 activity in nutritional programming so that it can be studied as a target for prevention of obesity in early life.

描述（由申请人提供）： 项目摘要：Jennifer K. Yee 是加州大学洛杉矶分校 Harbour 分校的儿科内分泌学家，她的学术生涯致力于研究硬脂酰辅酶 A 去饱和酶 1 (SCD1) 和脂肪酸合成途径在肥胖营养规划中的作用。作为一名研究员，Yee 博士在 W.N. Paul Lee 博士的指导下利用稳定同位素方法探索了 SCD1 抑制。受儿童肥胖症日益流行的推动，她将注意力转向 SCD1 在营养规划中的作用。 Yee博士的长期目标是成为一名独立研究者，通过研究脂肪生成和脂肪细胞分化中的脂肪酸代谢来确定肥胖的治疗和预防策略。叶博士的近期目标是确定她的研究重点，同时获得独立所需的技能。 Yee 博士提议的研究活动将得到教学教育的补充，包括加州大学洛杉矶分校 K30 项目和负责任的研究行为课程。 Yee 博士将接受中间代谢专家 W.N. Paul Lee 博士和营养规划食欲调节专家 Michael Ross 博士的共同资助。合作者 Mina Desai 也将支持 Yee 博士的研究培训。 Harbour-UCLA 为 Yee 博士提供了极好的学术环境，她将获得 75% 受保护时间的院系和部门支持，以及 GCRC 对她的项目的支持。临床、实验室和技术环境非常出色。该研究项目结合了临床和转化研究，旨在确定 SCD1 在产前和产后营养规划中的作用。该临床研究跟踪了三年来因宫内营养规划而面临肥胖风险的新生儿。代表 SCD1 活性的血浆脂肪酸比率（称为去饱和指数）将与身体成分和生化标记物一起每年进行测量。平行转化研究将测量肥胖营养规划大鼠模型中的去饱和指数以及 SCD1 基因和蛋白质表达。 SCD1 抑制的效果将在原代组织细胞培养物中进行离体研究，并在大鼠模型中进行体内研究。目的是建立这样的原理：SCD1 上调是子宫内编程的结果，并且抑制 SCD1 活性可以调节肥胖的发展。相关性：怀孕期间营养过多或过少（称为营养规划）可能导致后代肥胖和相关问题。 SCD1 酶活性增加导致脂肪酸合成途径发生变化，与肥胖、糖尿病和心脏病的发生有关。该项目的目标是确定 SCD1 活性在营养规划中的作用，以便将其作为预防生命早期肥胖的目标进行研究。