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Any deregulation leads either to fat overexpansion and obesity or fat loss and consequent lipodystrophies. Depending on the fat pad location, APs and adipocytes are heterogeneous. However, information on the pharmacological sensitivity of distinct APs to drugs known to alter the function of adipose tissue, especially HIV protease inhibitors (PIs) is scant. Here we show that PIs decreased proliferation and clonal expansion of APs, modifying their self-renewal potential. Lopinavir was the most potent PI tested. Decrease in self-renewal was accompanied by a reduced expression of the immediate early response gene IER3, a gene associated with tissue expansion. It was more pronounced in chin-derived APs than in knee-derived APs. Furthermore, lopinavir lowered the activin A\u2013induced ERK1\/2 phosphorylation. Expressions of the transcription factor EGR1 and its targets, including <jats:italic>INHBA<\/jats:italic> were subsequently altered. Therefore, activin A secretion was reduced leading to a dramatic impairment of APs self-renewal sustained by the activin A autocrine loop. All together, these observations highlight the activin A autocrine loop as a crucial effector to maintain APs self-renewal. Targeting this pathway by HIV-PIs may participate in the induction of unwanted side effects.<\/jats:p>","DOI":"10.1038\/s41598-017-02807-9","type":"journal-article","created":{"date-parts":[[2017,6,1]],"date-time":"2017-06-01T11:26:12Z","timestamp":1496316372000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Impairment of the activin A autocrine loop by lopinavir reduces self-renewal of distinct human adipose progenitors"],"prefix":"10.1038","volume":"7","author":[{"given":"Christophe","family":"Ravaud","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Par\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phane","family":"Azoulay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Dani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annie","family":"Ladoux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,6,7]]},"reference":[{"key":"2807_CR1","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1016\/j.cmet.2010.03.008","volume":"11","author":"S Enerback","year":"2010","unstructured":"Enerback, S. 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Characterization of human knee and chin adipose-derived stromal cells. Stem Cells Int \n                           2015, Epub 2015 Feb 2013 (2015).","DOI":"10.1155\/2015\/592090"},{"key":"2807_CR7","doi-asserted-by":"publisher","first-page":"2564","DOI":"10.1002\/stem.2016","volume":"33","author":"C Ravaud","year":"2015","unstructured":"Ravaud, C. et al. IER3 is a crucial effector promoting expansion of adipose progenitor cells in response to distinct micro-environmental effectors. Stem cells \n                           33, 2564\u20132573 (2015).","journal-title":"Stem cells"},{"key":"2807_CR8","doi-asserted-by":"publisher","first-page":"2513","DOI":"10.2337\/db10-0013","volume":"59","author":"LE Zaragosi","year":"2010","unstructured":"Zaragosi, L. E. et al. Activin a plays a critical role in proliferation and differentiation of human adipose progenitors. 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