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Bone-Adipose Interactions During Skeletal Anabolism

骨骼合成代谢过程中骨-脂肪相互作用

基本信息

批准号：
10202896
负责人：
Ryan C Riddle
金额：
$ 36.03万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-04-01 至 2026-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10202896
关键词：
Ablation Acute Address Adipocytes Adipose tissue Adrenergic Agents Anabolism Architecture Biochemistry Biology Bone Matrix Bone Tissue C57BL/6 Mouse Carbon Carnitine Palmitoyltransferase I Cell Lineage Cells Citric Acid Cycle Collaborations Data Deposition Development Distant Energy-Generating Resources Enzymes Epidemic Exercise Exercise Physiology Exposure to Fatty Acids Gene Expression Genetic Height Homeostasis Hormones Impairment In Vitro Interleukin-6 Label Laboratories Lead Lipase Lipolysis Manuscripts Mass Spectrum Analysis Mediating Metabolic dysfunction Mitochondria Modification Monitor Mus Obesity Osteoblasts Osteogenesis Osteopenia PTH gene Palmitates Performance Physiologic calcification Physiological Physiology Running Signal Transduction Societies Stimulus Therapeutic Therapeutic Effect Tissues Training Transgenic Mice Triglycerides Work bone bone mass bone strength extracellular fatty acid oxidation in vivo lipid metabolism long chain fatty acid microCT mouse model novel strategies osteoblast differentiation osteogenic oxidation receptor response skeletal skeletal stem cell treadmill uptake

项目摘要

Abstract Bone formation by osteoblasts requires significant energy input to fuel the synthesis, deposition, and mineralization of bone matrix. Fatty acids liberated by the lipolysis of triglycerides stored in adipose tissue are a rich source of energy that is used to fuel the energy-intensive functions of a number of tissues. In this application we will explore the interaction of bone and adipose tissue in response to two signals that stimulate new bone formation: intermittent parathyroid hormone administration and exercise. Both of these stimuli are also associated with increases in adipose tissue lipolysis. Our studies will determine the requirement for fatty acids to be transferred from adipose to osteoblasts by examining bone formation in transgenic mouse models in which lipolysis is impaired in adipocytes, via ablation of Atgl expression or fatty acid oxidation is impaired in osteoblasts, via the ablation of Cpt2 expression. Our hypothesis predicts that manipulation of lipid metabolism in either tissue will impair the bone formation response to each stimulus. Our approach will inform on the integrative physiologic networks that regulate skeletal homeostasis and the energy substrates required for bone formation during states of heighted anabolism. Additionally, these studies will enable us to define mechanisms by which obesity and metabolic dysfunction, conditions which are now epidemic in our society, inhibit bone formation

摘要