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This associates with, or is causative for increased atherosclerotic cardiovascular risk, ischemic stroke, fatty liver disease, and pancreatitis. TGRL hydrolysis by endothelial surface\u2010bound lipoprotein lipase (LPL) generates metabolites like free fatty acids which have proinflammatory properties. While osteoblasts utilize fatty acids as an energy source, dyslipidemia is associated with negative effects on the skeleton. In this study we investigated the effects of TGRL lipolysis products (TGRL\u2010LP) on expression of a stress responsive transcription factor, termed activating transcription factor 3 (ATF3), reactive oxygen species (ROS), ATF3 target genes, and angiopoietin\u2010like 4 (Angptl4) in osteoblasts. As ATF3 negatively associates with osteoblast differentiation, we also investigated the skeletal effects of global ATF3 deletion in mice. TGRL\u2010LP\u00a0increased expression of <jats:italic>Atf3<\/jats:italic>, proinflammatory proteins <jats:italic>Ptgs2<\/jats:italic> and <jats:italic>IL\u20106<\/jats:italic>, and induced ROS in MC3T3\u2010E1 osteoblastic cells. Angptl4 is an endogenous inhibitor of LPL which was transcriptionally induced by TGRL\u2010LP, while recombinant Angptl4 prevented TG\u2010driven <jats:italic>Atf3<\/jats:italic> induction. <jats:italic>Atf3<\/jats:italic> global knockout male mice demonstrated increased trabecular and cortical microarchitectural parameters. In summary, we find that TGRL\u2010LP induce osteoblastic cell stress as evidenced by expression of ATF3, which may contribute to the negative impact of dyslipidemia in the skeleton. Further, concomitant induction of <jats:italic>Angptl4<\/jats:italic> in osteoblasts might play a protective role by reducing local lipolysis.<\/jats:p>","DOI":"10.1002\/jor.25756","type":"journal-article","created":{"date-parts":[[2023,12,4]],"date-time":"2023-12-04T04:25:47Z","timestamp":1701663947000},"page":"1033-1044","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Lipolysis products from triglyceride\u2010rich lipoproteins induce stress protein ATF3 in osteoblasts"],"prefix":"10.1002","volume":"42","author":[{"given":"Jennifer M.","family":"Rutkowsky","sequence":"first","affiliation":[{"name":"Department of Molecular Biosciences, School of Veterinary Medicine University of California Davis Davis California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Wong","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Physiology and Cell Biology, School of 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