{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:39:22Z","timestamp":1790123962285,"version":"4.0.1"},"reference-count":32,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2019,5,20]],"date-time":"2019-05-20T00:00:00Z","timestamp":1558310400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2019,5,20]],"date-time":"2019-05-20T00:00:00Z","timestamp":1558310400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Cellular Biochemistry"],"published-print":{"date-parts":[[2019,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Apolipoprotein\u2010I (ApoA\u2010I), the major component of high\u2010density lipoprotein (HDL) particles, mediates cholesterol efflux by which it facilitates the removal of excess cholesterol from peripheral tissues. Therefore, elevating ApoA\u2010I production leading to the production of new pre\u2010\u03b2\u2010HDL particles is thought to be beneficial in the prevention of cardiovascular diseases. Recently, we observed that amoxicillin treatment led to decreased HDL concentrations in healthy human volunteers. We questioned whether this antibiotic effect was directly or indirectly, via changed short\u2010chain fatty acids (SCFA) concentrations through an altered gut microflora. Therefore, we here evaluated the effects of amoxicillin and various SCFA on hepatic ApoA\u2010I expression, secretion, and the putative underlying pathways.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and Results<\/jats:title>\n                    <jats:p>Human hepatocytes (HepG2) were exposed to increasing dose of amoxicillin or SCFA for 48\u2009\u2009hours. ApoA\u2010I messenger RNA (mRNA) transcription and secreted protein were analyzed using quantitative polymerase chain reaction and enzyme\u2010linked immunosorbent assay, respectively. To study underlying mechanisms, changes in mRNA expression of KEAP1, CPT1, and PPAR\u03b1, as well as a PPAR\u03b1 transactivation assay, were analyzed. Amoxicillin dose\u2010dependently decreased ApoA\u2010I mRNA transcription as well as ApoA\u2010I protein secretion. SCFA treatment resulted in a dose\u2010dependent stimulation of ApoA\u2010I mRNA transcription, however, the ApoA\u2010I protein secretion was decreased. Furthermore, SCFA treatment increased PPAR\u03b1 transactivation, PPAR\u03b1 and CPT1 mRNA transcription, whereas KEAP1 mRNA transcription was decreased.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Direct treatment of HepG2 cells with amoxicillin has either direct effects on lowering ApoA\u2010I transcription and secretion or indirect effects via modified SCFA concentrations because SCFA were found to stimulate hepatic ApoA\u2010I expression. Furthermore, BET inhibition and PPAR\u03b1 activation were identified as possible mechanisms behind the observed effects on ApoA\u2010I transcription.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcb.28982","type":"journal-article","created":{"date-parts":[[2019,5,20]],"date-time":"2019-05-20T05:00:40Z","timestamp":1558328440000},"page":"17219-17227","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["The effects of short\u2010chain fatty acids on the transcription and secretion of apolipoprotein A\u2010I in human hepatocytes in vitro"],"prefix":"10.1002","volume":"120","author":[{"given":"Jehad Z.","family":"Tayyeb","sequence":"first","affiliation":[{"name":"Department of Nutrition and Movement Sciences, NUTRIM School for Nutrition and Translational Research in Metabolism Maastricht University  Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0286-1966","authenticated-orcid":false,"given":"Herman E.","family":"Popeijus","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Movement Sciences, NUTRIM School for Nutrition and Translational Research in Metabolism Maastricht University  Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald P.","family":"Mensink","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Movement Sciences, NUTRIM School for Nutrition and Translational Research in Metabolism Maastricht University  Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurice C. J. M.","family":"Konings","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Movement Sciences, NUTRIM School for Nutrition and Translational Research in Metabolism Maastricht University  Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim H. R.","family":"Mulders","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Movement Sciences, NUTRIM School for Nutrition and Translational Research in Metabolism Maastricht University  Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jogchum","family":"Plat","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Movement Sciences, NUTRIM School for Nutrition and Translational Research in Metabolism Maastricht University  Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,5,20]]},"reference":[{"key":"e_1_2_8_1_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2016.06.016"},{"key":"e_1_2_8_1_3_1","unstructured":"deSmetE(2014).Plant Stanol Esters: focus On Intestinal Lipoprotein Metabolism[thesis]. Maastricht The Netherlands: Uitgeverij BOXPress Maastricht University. 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