{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T09:34:31Z","timestamp":1780565671212,"version":"3.54.1"},"reference-count":56,"publisher":"American Society for Clinical Investigation","issue":"18","license":[{"start":{"date-parts":[[2021,9,22]],"date-time":"2021-09-22T00:00:00Z","timestamp":1632268800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Gilead Sciences","award":["Gilead Sciences Research Scholars Program in HIV"],"award-info":[{"award-number":["Gilead Sciences Research Scholars Program in HIV"]}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["K23 HL136262"],"award-info":[{"award-number":["K23 HL136262"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01 DK082659"],"award-info":[{"award-number":["R01 DK082659"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["UL1 TR001102"],"award-info":[{"award-number":["UL1 TR001102"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["P30 DK040561"],"award-info":[{"award-number":["P30 DK040561"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["P30 DK046200"],"award-info":[{"award-number":["P30 DK046200"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Deutsche Forschungsgemeinschaft Fellowship","award":["DFG GA2426\/1-1"],"award-info":[{"award-number":["DFG GA2426\/1-1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,9,22]]},"abstract":"<jats:p>\n                    We identified a microRNA (miRNA) profile characterizing HIV lipodystrophy and explored the downstream mechanistic implications with respect to adipocyte biology and the associated clinical phenotype. miRNA profiles were extracted from small extracellular vesicles (sEVs) of HIV-infected individuals with and without lipodystrophic changes and individuals without HIV, among whom we previously showed significant reductions in adipose\n                    <jats:italic>Dicer<\/jats:italic>\n                    expression related to HIV. miR-20a-3p was increased and miR-324-5p and miR-186 were reduced in sEVs from HIV lipodystrophic individuals. Changes in these miRNAs correlated with adipose\n                    <jats:italic>Dicer<\/jats:italic>\n                    expression and clinical markers of lipodystrophy, including fat redistribution, insulin resistance, and hypertriglyceridemia. Human preadipocytes transfected with mimic miR-20a-3p, anti\u2013miR-324-5p, or anti\u2013miR-186 induced consistent changes in latent transforming growth factor beta binding protein 2 (\n                    <jats:italic>Ltbp2<\/jats:italic>\n                    ),\n                    <jats:italic>Wisp2<\/jats:italic>\n                    , and\n                    <jats:italic>Nebl<\/jats:italic>\n                    expression. Knockdown of\n                    <jats:italic>Ltbp2<\/jats:italic>\n                    downregulated markers of adipocyte differentiation (\n                    <jats:italic>Fabp4<\/jats:italic>\n                    ,\n                    <jats:italic>Ppar<\/jats:italic>\n                    \u03b3,\n                    <jats:italic>C\/ebpa<\/jats:italic>\n                    ,\n                    <jats:italic>Fasn<\/jats:italic>\n                    ,\n                    <jats:italic>adiponectin<\/jats:italic>\n                    ,\n                    <jats:italic>Glut4<\/jats:italic>\n                    ,\n                    <jats:italic>CD36<\/jats:italic>\n                    ), and\n                    <jats:italic>Lamin C<\/jats:italic>\n                    , and increased expression of genes involved in inflammation (\n                    <jats:italic>\n                      IL1\n                      <jats:bold\/>\n                    <\/jats:italic>\n                    <jats:italic>\u03b2<\/jats:italic>\n                    ,\n                    <jats:italic>IL6<\/jats:italic>\n                    , and\n                    <jats:italic>Ccl20<\/jats:italic>\n                    ). Our studies suggest a likely unique sEV miRNA signature related to dysregulation of\n                    <jats:italic>Dicer<\/jats:italic>\n                    in adipose tissue in HIV. Enhanced miR-20a-3p or depletion of miR-186 and miR-324-5p may downregulate\n                    <jats:italic>Ltbp2<\/jats:italic>\n                    in HIV, leading to dysregulation in adipose differentiation and inflammation, which could contribute to acquired HIV lipodystrophy and associated metabolic and inflammatory perturbations.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.150399","type":"journal-article","created":{"date-parts":[[2021,8,12]],"date-time":"2021-08-12T12:01:54Z","timestamp":1628769714000},"source":"Crossref","is-referenced-by-count":21,"title":["Altered pattern of circulating miRNAs in HIV lipodystrophy perturbs key adipose differentiation and inflammation pathways"],"prefix":"10.1172","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1950-4770","authenticated-orcid":true,"given":"Suman","family":"Srinivasa","sequence":"first","affiliation":[{"name":"Metabolism Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruben","family":"Garcia-Martin","sequence":"additional","affiliation":[{"name":"Section on Integrative Physiology and Metabolism, Joslin Diabetes Center and Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Torriani","sequence":"additional","affiliation":[{"name":"Division of Musculoskeletal Imaging and Intervention, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0541-3707","authenticated-orcid":true,"given":"Kathleen V.","family":"Fitch","sequence":"additional","affiliation":[{"name":"Metabolism Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna R.","family":"Carlson","sequence":"additional","affiliation":[{"name":"Metabolism Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7583-9228","authenticated-orcid":true,"given":"C. Ronald","family":"Kahn","sequence":"additional","affiliation":[{"name":"Section on Integrative Physiology and Metabolism, Joslin Diabetes Center and Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven K.","family":"Grinspoon","sequence":"additional","affiliation":[{"name":"Metabolism Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2021,9,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecl.2016.06.012"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofw098"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0000000000002060"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2014.8334"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3007148"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2015-3993"},{"issue":"3","key":"B7","doi-asserted-by":"crossref","DOI":"10.3390\/v10030110","article-title":"Are microRNAs important players in HIV-1 infection? An update","volume":"10","author":"Balasubramaniam","year":"2018","journal-title":"Viruses"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1172\/JCI73468"},{"issue":"6","key":"B9","first-page":"1201","article-title":"Fat-specific Dicer deficiency accelerates aging and mitigates several effects of dietary restriction in mice","volume":"8","author":"Reis","year":"2016","journal-title":"Aging (Albany NY)"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1097\/QAI.0b013e31815b0792"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1002\/oby.22742"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1007\/s11904-018-0411-2"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1038\/nature21365"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2019.07.011"},{"key":"B15","article-title":"Isolation and characterization of exosomes from cell culture supernatants and biological fluids","volume":"Chapter 3","author":"Thery","year":"2006","journal-title":"Curr Protoc Cell Biol"},{"key":"B16","unstructured":"GeneCards. LTBP2 Gene (Protein Coding). Latent Transforming Growth Factor Beta Binding Protein 2. https:\/\/www.genecards.org\/cgi-bin\/carddisp.pl?gene=LTBP2 Accessed August 20, 2021"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1038\/srep43515"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1211255110"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.2337\/db13-0473"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.2337\/db11-0075"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1038\/72807"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2002-021506"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1042\/BST20110675"},{"issue":"1\u20132","key":"B24","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.virol.2013.06.010","article-title":"The HIV-1 protein Vpr targets the endoribonuclease Dicer for proteasomal degradation to boost macrophage infection","volume":"444","author":"Casey Klockow","year":"2013","journal-title":"Virology"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1186\/1742-4690-3-95"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2011-2951"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2020.107286"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1007\/s10695-020-00877-7"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.7150\/thno.23334"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1615\/CritRevEukaryotGeneExpr.2020034571"},{"issue":"24","key":"B31","first-page":"12836","article-title":"MiRNA-324-5p inhibits inflammatory response of diabetic vessels by targeting CPT1A","volume":"24","author":"Wu","year":"2020","journal-title":"Eur Rev Med Pharmacol Sci"},{"issue":"1","key":"B32","first-page":"658","article-title":"Downregulated miRNA-324-5p aggravates neuronal injury induced by oxygen-glucose deprivation via modulating RAN","volume":"19","author":"Gu","year":"2020","journal-title":"Exp Ther Med"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1080\/15384101.2020.1826632"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2019.00461"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dku264"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1596"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1800"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(02)08094-7"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00391.2001"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2005.08.018"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1097\/00002030-200111090-00004"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.38341"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1086\/302836"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1002\/1098-1004(200012)16:6<451::AID-HUMU1>3.0.CO;2-9"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1097\/00002030-200311210-00005"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1097\/00002030-200308150-00004"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00206.2003"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1097\/GIM.0b013e3181632713"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1038\/nm0302-240"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.207738"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2021.100264"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2012.07.017"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-16340-3"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-7-261"},{"key":"B55","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.05005","article-title":"Predicting effective microRNA target sites in mammalian mRNAs","volume":"4","author":"Agarwal","year":"2015","journal-title":"Elife"},{"issue":"web server issue","key":"B56","doi-asserted-by":"crossref","first-page":"W169","DOI":"10.1093\/nar\/gkt393","article-title":"DIANA-microT web server v5.0: service integration into miRNA functional analysis workflows","volume":"41","author":"Paraskevopoulou","year":"2013","journal-title":"Nucleic Acids Res"}],"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/insight.jci.org\/articles\/view\/150399\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T23:44:26Z","timestamp":1779147866000},"score":1,"resource":{"primary":{"URL":"https:\/\/insight.jci.org\/articles\/view\/150399"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,22]]},"references-count":56,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2021,9,22]]},"published-print":{"date-parts":[[2021,9,22]]}},"alternative-id":["10.1172\/jci.insight.150399"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.150399","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,22]]},"article-number":"e150399"}}