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In a recent randomized placebo-controlled trial, we demonstrated that the growth hormone\u2013releasing hormone analog tesamorelin reduced liver fat and prevented fibrosis progression in HIV-associated NAFLD over 1 year. As such, tesamorelin is the first strategy that has shown to be effective against NAFLD among the population with HIV. The current study leveraged paired liver biopsy specimens from this trial to identify hepatic gene pathways that are differentially modulated by tesamorelin versus placebo. Using gene set enrichment analysis, we found that tesamorelin increased hepatic expression of hallmark gene sets involved in oxidative phosphorylation and decreased hepatic expression of gene sets contributing to inflammation, tissue repair, and cell division. Tesamorelin also reciprocally up- and downregulated curated gene sets associated with favorable and poor hepatocellular carcinoma prognosis, respectively. 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Our findings inform our knowledge of the biology of pulsatile growth hormone action and provide a mechanistic basis for the observed clinical effects of tesamorelin on the liver.<\/jats:p>","DOI":"10.1172\/jci.insight.140134","type":"journal-article","created":{"date-parts":[[2020,7,23]],"date-time":"2020-07-23T12:03:14Z","timestamp":1595505794000},"source":"Crossref","is-referenced-by-count":24,"title":["Effects of tesamorelin on hepatic transcriptomic signatures in HIV-associated NAFLD"],"prefix":"10.1172","volume":"5","author":[{"given":"Lindsay T.","family":"Fourman","sequence":"first","affiliation":[{"name":"Metabolism Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James M.","family":"Billingsley","sequence":"additional","affiliation":[{"name":"Harvard Chan Bioinformatics Core, Department of Biostatistics, Harvard T.H. 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