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

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Bone Research 2023年第4期11卷 876-894页

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 Department of Medicine Division of Clinical PharmacologyVanderbilt University Medical CenterNashvilleTN 37232USA Program in Molecular Medicine University of Massachusetts Chan Medical SchoolWorcesterMA 01605USA Maine Medical Center Research Institute ScarboroughMEUSA Molecular Physiology and Biophysics Vanderbilt UniversityNashvilleTN 37232USA

Bone formation is a highly energy-demanding process that can be impacted by metabolic *** has been considered the principal substrate for osteoblasts,although fatty acids are also important for osteoblast ***,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 *** 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 *** cytoplasmic lipolysis leads to both an increase in lipid droplet size in osteoblasts and an impairment in osteoblast *** 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 *** vivo,conditional deletion of the ATGL-encoding gene Pnpla2 in osteoblast progenitor cells reduces cortical and trabecular bone parameters and alters skeletal lipid ***,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 *** in this process result in impairment of bone formation,specifically reducing ATP production and overall osteoblast function.

关键词： endogenous maintain osteoblast

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