{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T10:43:36Z","timestamp":1789728216707,"version":"4.0.1"},"reference-count":49,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2018,1]]},"abstract":"<jats:sec>\n            <jats:title>Objective\u2014<\/jats:title>\n            <jats:p>Type 2 diabetes mellitus (T2DM) and the atherometabolic syndrome exhibit a deadly dyslipoproteinemia that arises in part from impaired hepatic disposal of C-TRLs (cholesterol- and triglyceride-rich remnant apoB [apolipoprotein B] lipoproteins). We previously identified syndecan-1 as a receptor for C-TRLs that directly mediates endocytosis via rafts, independent from coated pits. Caveolins and flotillins form rafts but facilitate distinct endocytotic pathways. We now investigated their participation in syndecan-1\u2013mediated disposal of C-TRLs and their expression in T2DM liver.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results\u2014<\/jats:title>\n            <jats:p>\n              In cultured liver cells and nondiabetic murine livers, we found that syndecan-1 coimmunoprecipitates with FLOT1 (flotillin-1) but not with CAV1 (caveolin-1). Binding of C-TRLs to syndecan-1 on the surface of liver cells enhanced syndecan-1\/FLOT1 association. The 2 molecules then trafficked together into the lysosomes, implying limited if any recycling back to the cell surface. The interaction requires the transmembrane\/cytoplasmic region of syndecan-1 and the N-terminal hydrophobic domain of FLOT1. Knockdown of FLOT1 in cultured liver cells substantially inhibited syndecan-1 endocytosis. Livers from obese, T2DM KK\n              <jats:italic>A<\/jats:italic>\n              <jats:sup>\n                <jats:italic>y<\/jats:italic>\n              <\/jats:sup>\n              mice exhibited 60% to 70% less FLOT1 protein and mRNA than in nondiabetic KK livers. An adenoviral construct to enhance hepatic expression of wild-type FLOT1 in T2DM mice normalized plasma triglycerides, whereas a mutant FLOT1 missing its N-terminal hydrophobic domain had no effect. Moreover, the adenoviral vector for wild-type FLOT1 lowered plasma triglyceride excursions and normalized retinyl excursions in T2DM KK\n              <jats:italic>A<\/jats:italic>\n              <jats:sup>\n                <jats:italic>y<\/jats:italic>\n              <\/jats:sup>\n              mice after a corn oil gavage, without affecting postprandial production of C-TRLs.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>FLOT1 is a novel participant in the disposal of harmful C-TRLs via syndecan-1. Low expression of FLOT1 in T2DM liver may contribute to metabolic dyslipoproteinemia.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.117.310358","type":"journal-article","created":{"date-parts":[[2017,11,21]],"date-time":"2017-11-21T10:00:49Z","timestamp":1511258449000},"page":"102-113","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":24,"title":["Suppression of Hepatic FLOT1 (Flotillin-1) by Type 2 Diabetes Mellitus Impairs the Disposal of Remnant Lipoproteins via Syndecan-1"],"prefix":"10.1161","volume":"38","author":[{"given":"Keyang","family":"Chen","sequence":"first","affiliation":[{"name":"From the School of Public Health (K.C., Q.W., C.Y.) and Department of Surgery, The First Affiliated Hospital (K.H.), Anhui Medical University, Hefei, China; Section of Endocrinology, Diabetes, &amp; Metabolism, Department of Medicine, Lewis Katz School of Medicine at Temple University, Philadelphia, PA (K.C., X.W., P.C., K.J.W.); and Department of Molecular and Clinical Medicine, Sahlgrenska Academy of the University of Gothenburg, Sweden (K.J.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingsi","family":"Wu","sequence":"additional","affiliation":[{"name":"From the School of Public Health (K.C., Q.W., C.Y.) and Department of Surgery, The First Affiliated Hospital (K.H.), Anhui Medical University, Hefei, China; Section of Endocrinology, Diabetes, &amp; Metabolism, Department of Medicine, Lewis Katz School of Medicine at Temple University, Philadelphia, PA (K.C., X.W., P.C., K.J.W.); and Department of Molecular and Clinical Medicine, Sahlgrenska Academy of the University of Gothenburg, Sweden (K.J.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kongwang","family":"Hu","sequence":"additional","affiliation":[{"name":"From the School of Public Health (K.C., Q.W., C.Y.) and Department of Surgery, The First Affiliated Hospital (K.H.), Anhui Medical University, Hefei, China; Section of Endocrinology, Diabetes, &amp; Metabolism, Department of Medicine, Lewis Katz School of Medicine at Temple University, Philadelphia, PA (K.C., X.W., P.C., K.J.W.); and Department of Molecular and Clinical Medicine, Sahlgrenska Academy of the University of Gothenburg, Sweden (K.J.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengwei","family":"Yang","sequence":"additional","affiliation":[{"name":"From the School of Public Health (K.C., Q.W., C.Y.) and Department of Surgery, The First Affiliated Hospital (K.H.), Anhui Medical University, Hefei, China; Section of Endocrinology, Diabetes, &amp; Metabolism, Department of Medicine, Lewis Katz School of Medicine at Temple University, Philadelphia, PA (K.C., X.W., P.C., K.J.W.); and Department of Molecular and Clinical Medicine, Sahlgrenska Academy of the University of Gothenburg, Sweden (K.J.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangdong","family":"Wu","sequence":"additional","affiliation":[{"name":"From the School of Public Health (K.C., Q.W., C.Y.) and Department of Surgery, The First Affiliated Hospital (K.H.), Anhui Medical University, Hefei, China; Section of Endocrinology, Diabetes, &amp; Metabolism, Department of Medicine, Lewis Katz School of Medicine at Temple University, Philadelphia, PA (K.C., X.W., P.C., K.J.W.); and Department of Molecular and Clinical Medicine, Sahlgrenska Academy of the University of Gothenburg, Sweden (K.J.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Cheung","sequence":"additional","affiliation":[{"name":"From the School of Public Health (K.C., Q.W., C.Y.) and Department of Surgery, The First Affiliated Hospital (K.H.), Anhui Medical University, Hefei, China; Section of Endocrinology, Diabetes, &amp; Metabolism, Department of Medicine, Lewis Katz School of Medicine at Temple University, Philadelphia, PA (K.C., X.W., P.C., K.J.W.); and Department of Molecular and Clinical Medicine, Sahlgrenska Academy of the University of Gothenburg, Sweden (K.J.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin Jon","family":"Williams","sequence":"additional","affiliation":[{"name":"From the School of Public Health (K.C., Q.W., C.Y.) and Department of Surgery, The First Affiliated Hospital (K.H.), Anhui Medical University, Hefei, China; Section of Endocrinology, Diabetes, &amp; Metabolism, Department of Medicine, Lewis Katz School of Medicine at Temple University, Philadelphia, PA (K.C., X.W., P.C., K.J.W.); and Department of Molecular and Clinical Medicine, Sahlgrenska Academy of the University of Gothenburg, Sweden (K.J.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)60367-5"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1410489"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1501031"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1615664"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.115.307609"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1097\/MOL.0000000000000330"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2016.02.004"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2015.01.039"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.15.5.551"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M204053200"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000174795.62387.d3"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1097\/MOL.0b013e328338cabc"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2012.08.1026"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0807646"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2004.09.034"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1316222"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.116.025253"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119685"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj3510607"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.1097\/00041433-199710000-00003"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI38251"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.444737"},{"key":"e_1_3_5_24_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.21.13793"},{"key":"e_1_3_5_25_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.78.081307.110540"},{"key":"e_1_3_5_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1342"},{"key":"e_1_3_5_27_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1014434108"},{"key":"e_1_3_5_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature03866"},{"key":"e_1_3_5_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2122"},{"key":"e_1_3_5_30_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0854.2007.00540.x"},{"key":"e_1_3_5_31_2","doi-asserted-by":"publisher","DOI":"10.1385\/1-59259-209-0:457"},{"key":"e_1_3_5_32_2","first-page":"E","article-title":"An unexpected consensus motif shared by the LDL receptor and syndecan transmembrane domains directs movement into rafts upon clustering.","volume":"24","author":"Liu M-L","year":"2004","unstructured":"Liu M-L, Davidson WR, Meyer ME, Friedman RA, Williams KJ. 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