{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T09:11:10Z","timestamp":1785489070379,"version":"3.56.0"},"reference-count":43,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","license":[{"start":{"date-parts":[[2022,10,12]],"date-time":"2022-10-12T00:00:00Z","timestamp":1665532800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/ http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:sec>\n            <jats:title>Background and Aims:<\/jats:title>\n            <jats:p>The assembly and secretion of VLDL from the liver, a pathway that affects hepatic and plasma lipids, remains incompletely understood. We set out to identify players in the VLDL biogenesis pathway by identifying genes that are co\u2212expressed with the <jats:italic toggle=\"yes\">MTTP<\/jats:italic> gene that encodes for microsomal triglyceride transfer protein, key to the lipidation of apolipoprotein B, the core protein of VLDL. Using human and murine transcriptomic data sets, we identified small leucine\u2212rich protein 1 (<jats:italic toggle=\"yes\">SMLR1<\/jats:italic>), encoding for small leucine\u2212rich protein 1, a protein of unknown function that is exclusively expressed in liver and small intestine.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results:<\/jats:title>\n            <jats:p>To assess the role of SMLR1 in the liver, we used somatic CRISPR\/CRISPR\u2212associated protein 9 gene editing to silence murine <jats:italic toggle=\"yes\">Smlr1<\/jats:italic> in hepatocytes (<jats:italic toggle=\"yes\">Smlr1<\/jats:italic>\u2212LKO). When fed a chow diet, male and female mice show hepatic steatosis, reduced plasma apolipoprotein B and triglycerides, and reduced VLDL secretion without affecting microsomal triglyceride transfer protein activity. Immunofluorescence studies show that SMLR1 is in the endoplasmic reticulum and Cis\u2212Golgi complex. The loss of hepatic SMLR1 in female mice protects against diet\u2212induced hyperlipidemia and atherosclerosis but causes NASH. On a high\u2212fat, high\u2212cholesterol diet, insulin and glucose tolerance tests did not reveal differences in male <jats:italic toggle=\"yes\">Smlr1<\/jats:italic>\u2212LKO mice versus controls.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>We propose a role for SMLR1 in the trafficking of VLDL from the endoplasmic reticulum to the Cis\u2212Golgi complex. While this study uncovers SMLR1 as a player in the VLDL assembly, trafficking, and secretion pathway, it also shows that NASH can occur with undisturbed glucose homeostasis and atheroprotection.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.32709","type":"journal-article","created":{"date-parts":[[2022,9,2]],"date-time":"2022-09-02T10:00:16Z","timestamp":1662112816000},"page":"1418-1432","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":19,"title":["Loss of hepatic SMLR1 causes hepatosteatosis and protects against atherosclerosis due to decreased hepatic VLDL secretion"],"prefix":"10.1097","volume":"78","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2298-6563","authenticated-orcid":false,"given":"Willemien","family":"van Zwol","sequence":"first","affiliation":[{"name":"Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2971-4926","authenticated-orcid":false,"given":"Antoine","family":"Rimbert","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Nantes, CNRS, INSERM, l'institut du thorax, Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justina C.","family":"Wolters","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marieke","family":"Smit","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent W.","family":"Bloks","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niels J.","family":"Kloosterhuis","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolette C. A.","family":"Huijkman","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirjam H.","family":"Koster","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Umesh","family":"Tharehalli","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon M.","family":"de Neck","sequence":"additional","affiliation":[{"name":"Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin","family":"Bournez","sequence":"additional","affiliation":[{"name":"Division of Drug Discovery and Safety, Leiden Academic Center for Drug Research, Leiden University, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marceline M.","family":"Fuh","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg\u2212Eppendorf, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeroen","family":"Kuipers","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences of Cells and Systems, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sujith","family":"Rajan","sequence":"additional","affiliation":[{"name":"Department of Foundations of Medicine, NYU Long Island School of Medicine, Mineola, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alain","family":"de Bruin","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands"},{"name":"Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry N.","family":"Ginsberg","sequence":"additional","affiliation":[{"name":"Department of Medicine, Columbia University, Vagelos College of Physicians and Surgeons, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0717-1817","authenticated-orcid":false,"given":"Gerard J. 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