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Interaction between Hormone-Sensitive Lipase and ChREBP in Fat Cells Controls Insulin Sensitivity

Morigny, Pauline, Houssier, Marianne, Mairal, Aline, Ghilain, Claire, Etienne, Mouisel, Benhamed, Fadila, Masri, Bernard, Recazens, Emeline, Denechaud, Pierre-Damien, Tavernier, Geneviève , Caspar-Bauguil, Sylvie, Virtue, Sam, Sramkova, Veronika, Monbrun, Laurent, Mazars, Anne, Zazoun, Madjid, Guilmeau, Sandra, Barquissau, Valentin, Beuzelin, Diane, Bonnel, Sophie, Marques, Marie, Monge-Roffarello, Boris, Lefort, Corinne, Fielding, Barbara, Sulpice, Thierry, Astrup, Arne, Payrastre, Bernard, Bertrand-Michel, Justine, Meugnier, Emmanuelle, Ligat, Laetitia, Lopez, Frederic, Guillou, Hervé, Ling, Charlotte, Holm, Cecilia, Rabasa-Lhoret, Remi, Saris, Wim, Stich, Vladimir, Arner, Peter, Ryden, Mikael, Moro, Cedric, Viguerie, Nathalie, Harms, Matthew, Hallén, Stefan, Vidal-Puig, Antonio, Vidal, Hubert, Postic, Catherine and Langin, Dominique (2018) Interaction between Hormone-Sensitive Lipase and ChREBP in Fat Cells Controls Insulin Sensitivity Nature Metabolism.

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Impaired adipose tissue insulin signalling is a critical feature of insulin resistance. Here we identify a pathway linking the lipolytic enzyme hormone-sensitive lipase (HSL) to insulin action via the glucose-responsive transcription factor ChREBP and its target, the fatty acid elongase ELOVL6. Genetic inhibition of HSL in human adipocytes and mouse adipose tissue results in enhanced insulin sensitivity and induction of ELOVL6. ELOVL6 promotes an increase in phospholipid oleic acid, which modifies plasma membrane fluidity and enhances insulin signalling. HSL deficiency–mediated effects are suppressed by gene silencing of ChREBP and ELOVL6. Mechanistically, physical interaction between HSL, independent of lipase activity, and the isoform activated by glucose metabolism ChREBPα impairs ChREBPα translocation into the nucleus and induction of ChREBPβ, the isoform with high transcriptional activity that is strongly associated with whole-body insulin sensitivity. Targeting the HSL–ChREBP interaction may allow therapeutic strategies for the restoration of insulin sensitivity.

Item Type: Article
Divisions : Faculty of Health and Medical Sciences > School of Biosciences and Medicine
Authors :
Morigny, Pauline
Houssier, Marianne
Mairal, Aline
Ghilain, Claire
Etienne, Mouisel
Benhamed, Fadila
Masri, Bernard
Recazens, Emeline
Denechaud, Pierre-Damien
Tavernier, Geneviève
Caspar-Bauguil, Sylvie
Virtue, Sam
Sramkova, Veronika
Monbrun, Laurent
Mazars, Anne
Zazoun, Madjid
Guilmeau, Sandra
Barquissau, Valentin
Beuzelin, Diane
Bonnel, Sophie
Marques, Marie
Monge-Roffarello, Boris
Lefort, Corinne
Sulpice, Thierry
Astrup, Arne
Payrastre, Bernard
Bertrand-Michel, Justine
Meugnier, Emmanuelle
Ligat, Laetitia
Lopez, Frederic
Guillou, Hervé
Ling, Charlotte
Holm, Cecilia
Rabasa-Lhoret, Remi
Saris, Wim
Stich, Vladimir
Arner, Peter
Ryden, Mikael
Moro, Cedric
Viguerie, Nathalie
Harms, Matthew
Hallén, Stefan
Vidal-Puig, Antonio
Vidal, Hubert
Postic, Catherine
Langin, Dominique
Date : 3 December 2018
DOI : 10.1038/s42255-018-0007-6
Copyright Disclaimer : © The Author(s), under exclusive licence to Springer Nature Limited 2018
Related URLs :
Depositing User : Clive Harris
Date Deposited : 01 Nov 2018 08:52
Last Modified : 05 Dec 2018 09:45

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