LEPROT and LEPROTL1 cooperatively decrease hepatic growth hormone action in mice
| Autor: | Touvier, Thierry, Conte-Auriol, Françoise, Briand, Olivier, Cudejko, Céline, Paumelle, Réjane, Caron, Sandrine, Baugé, Eric, Rouillé, Yves, Salles, Jean-Pierre, Staels, Bart, Bailleul, Bernard |
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| Přispěvatelé: | Récepteurs nucléaires, lipoprotéines et athérosclérose, Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de biologie de Lille - IBL (IBLI), Université de Lille, Sciences et Technologies-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
MESH: Signal Transduction
MESH: Humans MESH: Rats MESH: Mice Transgenic MESH: STAT5 Transcription Factor MESH: RNA Interference MESH: Fasting MESH: Carrier Proteins MESH: Suppressor of Cytokine Signaling Proteins MESH: Male MESH: Cell Line MESH: Recombinant Proteins MESH: Hepatocytes MESH: Mice Inbred C57BL MESH: Growth Hormone MESH: Diabetes Mellitus Experimental MESH: Animals [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology MESH: Mice MESH: Receptors Somatotropin MESH: Female MESH: RNA Messenger MESH: Liver |
| Zdroj: | Journal of Clinical Investigation Journal of Clinical Investigation, American Society for Clinical Investigation, 2009, 119 (12), pp.3830-8. ⟨10.1172/JCI34997⟩ |
| ISSN: | 0021-9738 |
| DOI: | 10.1172/JCI34997⟩ |
| Popis: | International audience; Growth hormone (GH) is a major metabolic regulator that functions by stimulating lipolysis, preventing protein catabolism, and decreasing insulin-dependent glucose disposal. Modulation of hepatic sensitivity to GH and the downstream effects on the GH/IGF1 axis are important events in the regulation of metabolism in response to variations in food availability. For example, during periods of reduced nutrient availability, the liver becomes resistant to GH actions. However, the mechanisms controlling hepatic GH resistance are currently unknown. Here, we investigated the role of 2 tetraspanning membrane proteins, leptin receptor overlapping transcript (LEPROT; also known as OB-RGRP) and LEPROT-like 1 (LEPROTL1), in controlling GH sensitivity. Transgenic mice expressing either human LEPROT or human LEPROTL1 displayed growth retardation, reduced plasma IGF1 levels, and impaired hepatic sensitivity to GH, as measured by STAT5 phosphorylation and Socs2 mRNA expression. These phenotypes were accentuated in transgenic mice expressing both proteins. Moreover, gene silencing of either endogenous Leprot or Leprotl1 in H4IIE hepatocytes increased GH signaling and enhanced cell-surface GH receptor. Importantly, we found that both LEPROT and LEPROTL1 expression were regulated in the mouse liver by physiologic and pathologic changes in glucose homeostasis. Together, these data provide evidence that LEPROT and LEPROTL1 influence liver GH signaling and that regulation of the genes encoding these proteins may constitute a molecular link between nutritional signals and GH actions on body growth and metabolism. |
| Databáze: | OpenAIRE |
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