Lipolysis supports bone formation by providing osteoblasts with endogenous fatty acid substrates to maintain bioenergetic status  

作　　者：Ananya Nandy Ron C.M.Helderman Santosh Thapa Shobana Jayapalan Alison Richards Nikita Narayani Michael P.Czech Clifford J.Rosen Elizabeth Rendina-Ruedy 

机构地区：[1]Department of Medicine,Division of Clinical Pharmacology,Vanderbilt University Medical Center,Nashville,TN 37232,USA [2]Program in Molecular Medicine,University of Massachusetts Chan Medical School,Worcester,MA 01605,USA [3]Maine Medical Center Research Institute,Scarborough,ME,USA [4]Molecular Physiology and Biophysics,Vanderbilt University,Nashville,TN 37232,USA

出　　处：《Bone Research》2023年第4期876-894,共19页骨研究（英文版）

基　　金：supported by National Institutes of Health(NIH),the National Institute of Arthritis and Musculoskeletal and Skin Diseases(NIAMS)Grant K01AR072123(ER-R);the American Society of Bone and Mineral Research(ASBMR)Rising Star award;provided by NIH-National Institute of Diabetes and Digestive and Kidney Disease(NIDDK)Grant DK116056(MPC)。

摘　　要：Bone formation is a highly energy-demanding process that can be impacted by metabolic disorders.Glucose has been considered the principal substrate for osteoblasts,although fatty acids are also important for osteoblast function.Here,we report that osteoblasts can derive energy from endogenous fatty acids stored in lipid droplets via lipolysis and that this process is critical for bone formation.As such,we demonstrate that osteoblasts accumulate lipid droplets that are highly dynamic and provide the molecular mechanism by which they serve as a fuel source for energy generation during osteoblast maturation.Inhibiting cytoplasmic lipolysis leads to both an increase in lipid droplet size in osteoblasts and an impairment in osteoblast function.The fatty acids released by lipolysis from these lipid droplets become critical for cellular energy production as cellular energetics shifts towards oxidative phosphorylation during nutrient-depleted conditions.In vivo,conditional deletion of the ATGL-encoding gene Pnpla2 in osteoblast progenitor cells reduces cortical and trabecular bone parameters and alters skeletal lipid metabolism.Collectively,our data demonstrate that osteoblasts store fatty acids in the form of lipid droplets,which are released via lipolysis to support cellular bioenergetic status when nutrients are limited.Perturbations in this process result in impairment of bone formation,specifically reducing ATP production and overall osteoblast function.

关 键 词：ENDOGENOUS MAINTAIN OSTEOBLAST 

分 类 号：R68[医药卫生—骨科学]