ANGPTL4 is a potential driver of HCV-induced peripheral insulin resistance

Article Article scientifique Article ANGPTL4 is a potential driver of HCV-induced peripheral insulin resistance eng 2023-04-25 2023-04-25 author Rocha Gomes Diana Bianca 844324 author Sobolewski Cyril 819918 author Conzelmann-Prin Stéphanie 638487 Département de médecine génétique et développement (GEDEV) Stéphanie Conzelmann author Schaer Tifany 740855 Département de médecine (DEMED) author Lefai Etienne 0000-0002-3042-7801 author Alfaiate Dulce 855561 author Tseligka Eirini 845127 author Goossens Nicolas 509893 Département de médecine (DEMED) author Tapparel Caroline 0000-0002-0411-6567 27039 Département de microbiologie et médecine moléculaire (MIMOL) author Negro Francesco 96509 Décanat et administration de la faculté de médecine (ADMED) author Foti Michelangelo 0000-0001-7199-4135 28033 Département de physiologie cellulaire et métabolisme (PHYME) author Clément Leboube Sophie 120543 Département de microbiologie et médecine moléculaire (MIMOL) Sophie Clément 6767 10.1038/s41598-023-33728-5 37185283 2045-2322 PMC10130097 https://www.nature.com/articles/s41598-023-33728-5 Chronic hepatitis C (CHC) is associated with the development of metabolic disorders, including both hepatic and extra-hepatic insulin resistance (IR). Here, we aimed at identifying liver-derived factor(s) potentially inducing peripheral IR and uncovering the mechanisms whereby HCV can regulate the action of these factors. We found ANGPTL4 (Angiopoietin Like 4) mRNA expression levels to positively correlate with HCV RNA (r = 0.46, p < 0.03) and HOMA-IR score (r = 0.51, p = 0.01) in liver biopsies of lean CHC patients. Moreover, we observed an upregulation of ANGPTL4 expression in two models recapitulating HCV-induced peripheral IR, i.e. mice expressing core protein of HCV genotype 3a (HCV-3a core) in hepatocytes and hepatoma cells transduced with HCV-3a core. Treatment of differentiated myocytes with recombinant ANGPTL4 reduced insulin-induced Akt-Ser473 phosphorylation. In contrast, conditioned medium from ANGPTL4 -KO hepatoma cells prevented muscle cells from HCV-3a core induced IR. Treatment of HCV-3a core expressing HepG2 cells with PPARγ antagonist resulted in a decrease of HCV-core induced ANGPTL4 upregulation. Together, our data identified ANGPTL4 as a potential driver of HCV-induced IR and may provide working hypotheses aimed at understanding the pathogenesis of IR in the setting of other chronic liver disorders. Dewey 612 Dewey 616 Dewey 616.07 Swiss National Science Foundation Hepatitis C virus and glucose and lipid metabolism: molecular interactions and significance 166609 CH Projects Swiss National Science Foundation Hepatitis C virus infection as a model for hepatogenous glucose homeostasis alterations 184663 CH Projects Swiss National Science Foundation Elucidating the role of S100A10 and S100A11 in NASH and HCC development 200530 CH Projects 54 Département de microbiologie et médecine moléculaire 21B 137 Département de pathologie et immunologie 21F 56 Département de médecine 221 134 Département de physiologie cellulaire et métabolisme 21C false 931 Identification des facteurs clés impliqués dans la pathogénèse des rhinovirus et entérovirus 953 297 Etudes et traitement de l'hépatite C et B 554 472 Obésité et syndrome métabolique 803 Scientific reports 13 1 47af9042-97b6-4980-ba59-6f941339f9f6 Article (Published version) Public Article-scientifique-from-unpaywall.pdf 2126234 application/pdf CC BY-4.0 9e122d9ef994889fe356b6aef68b7a4ff5652b76073068e88e3854b38e67fbcb e1a50890-2de8-4908-a93f-c02b5dd52d43 Supplemental data Public 41598_2023_33728_MOESM1_ESM.docx 17775902 application/vnd.openxmlformats-officedocument.wordprocessingml.document df65712777d5c43dc6a6a5756207de84be01f067afa21e33fad9c7df040d8120 openAccess Faculté de médecine / Section de médecine fondamentale / Département de microbiologie et médecine moléculaire Faculté de médecine / Section de médecine fondamentale / Département de pathologie et immunologie Faculté de médecine / Section de médecine clinique / Département de médecine Faculté de médecine / Section de médecine fondamentale / Département de physiologie cellulaire et métabolisme

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ANGPTL4 is a potential driver of HCV-induced peripheral insulin resistance	Scientific reports			2023	128	35

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