title: VISFATIN (NAMPT) Improves In Vitro IGF1-Induced Steroidogenesis and IGF1 Receptor Signaling Through SIRT1 in Bovine Granulosa Cells.
abstract: VISFATIN is a novel adipokine, also known as a nicotinamide phosphorybosyltransferase (NAMPT), that is able to modulate different processes, including lipid and glucose metabolism, oxidative stress, inflammation, and insulin resistance. Recent data suggest that it also plays a role in reproductive function in rats, humans, and chickens. Here we identified VISFATIN in the bovine ovary and investigated the in vitro effects of this hormone on granulosa cell steroidogenesis and proliferation and oocyte maturation. By RT-PCR, immunoblotting, and immunohistochemistry, we found VISFATIN in various ovarian cells, including granulosa and theca cells, corpus luteum, and oocytes. In cultured bovine granulosa cells, we showed that IGF1 (10(-8) M) and VISFATIN (10 and 100 ng/ml) but not FSH (10(-8) M) increased mRNA expression levels of NAMPT after 48 h of stimulation. Moreover, we observed that human recombinant VISFATIN (hVisf, 10 ng/ml, 48 h) increased the release of progesterone and estradiol secretion, and this was associated with an increase in the protein level of STAR, the HSD3B activity, and the phosphorylation levels of IGF1R and MAPK ERK1/2 in the presence or absence of IGF1 (10(-8) M). All these effects were abolished when NAMPT was knocked down and when the sirtuin pharmacological inhibitors CHIC-35 (60 nM) and EX-527 (0.5 μM) were preincubated in bovine granulosa cells. Thus, in cultured bovine granulosa cells, VISFATIN improves basal and IGF1-induced steroidogenesis and IGF1 receptor signaling through SIRT1.
authors.affiliation: Unité Mixte de Recherches 7247 Institut National de la Recherche Agronomique-Centre National de la Recherche Scientifique-Université de Tours-Institut Français du Cheval et de l'Equitation, Nouzilly, France.
authors.forename: Maxime
authors.initials: M
authors.lastname: Reverchon
authors.affiliation: Unité Mixte de Recherches 7247 Institut National de la Recherche Agronomique-Centre National de la Recherche Scientifique-Université de Tours-Institut Français du Cheval et de l'Equitation, Nouzilly, France.
authors.forename: Christelle
authors.initials: C
authors.lastname: Rame
authors.affiliation: Unité Mixte de Recherches 7247 Institut National de la Recherche Agronomique-Centre National de la Recherche Scientifique-Université de Tours-Institut Français du Cheval et de l'Equitation, Nouzilly, France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Bunel
authors.affiliation: Beckman Research Institute of the City of Hope, Duarte, California.
authors.forename: Wenyong
authors.initials: W
authors.lastname: Chen
authors.affiliation: Unité Mixte de Recherches 7247 Institut National de la Recherche Agronomique-Centre National de la Recherche Scientifique-Université de Tours-Institut Français du Cheval et de l'Equitation, Nouzilly, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Froment
authors.affiliation: Unité Mixte de Recherches 7247 Institut National de la Recherche Agronomique-Centre National de la Recherche Scientifique-Université de Tours-Institut Français du Cheval et de l'Equitation, Nouzilly, France jdupont@tours.inra.fr.
authors.forename: Joëlle
authors.initials: J
authors.lastname: Dupont
mesh_terms: D000818:Animals; D002417:Cattle; D004958:Estradiol / Q000096:biosynthesis; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006107:Granulosa Cells / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D054409:Nicotinamide Phosphoribosyltransferase / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D011374:Progesterone / Q000096:biosynthesis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017451:Receptors, Somatomedin / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology*; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism*; D013256:Steroids / Q000096:biosynthesis*
chemical_list: D012333:RNA, Messenger; D017451:Receptors, Somatomedin; D011994:Recombinant Proteins; D013256:Steroids; D011374:Progesterone; D004958:Estradiol; D007334:Insulin-Like Growth Factor I; D005640:Follicle Stimulating Hormone; D054409:Nicotinamide Phosphoribosyltransferase; D056564:Sirtuin 1
keywords: adipokine; granulosa; ovary; reproduction; signaling pathways